late transition metal complexes bearing functionalized n

Late Transition Metal Complexes Bearing Functionalized N-Heterocyclic Carbenes

and the Catalytic Hydrogenation of Polar Double Bonds

by

Wylie Wing Nien O

A thesis submitted in conformity with the requirements

for the degree of Doctor of Philosophy

Graduate Department of Chemistry

University of Toronto

© Copyright by Wylie Wing Nien O 2012

iiLATE TRANSITION METALS COMPLEXES BEARING FUNCTIONALIZED

N-HETETROCYCLIC CARBENES AND THE CATALYTIC HYDROGENATION OF POLAR

DOUBLE BONDS

Wylie Wing Nien O

Doctor of Philosophy

Department of Chemistry

University of Toronto

2012

Abstract

Late transition metal complexes of silver(I), rhodium(I), ruthenium(II), palladium(II) and

platinum(II) containing a nitrile-functionalized N-heterocyclic carbene ligand (C–CN) were

prepared. The nitrile group on the C–CN ligand was shown to undergo hydrolysis under basic

conditions, leading to a silver(I) carbene complex with a primary-amido functional group, and a

trimetallic complex of palladium(II) with a partially hydrolyzed C–N–N–C donor ligand.

The reduction of a nitrile-functionalized imidazolium salt in the presence of nickel(II)

chloride under mild conditions yielded an axially chiral square-planar nickel(II) complex

containing a unique primary-amino functionalized N-heterocyclic carbene ligand (C–NH2). A

transmetalation reaction moved this chelating C–NH2 ligand from nickel(II) to ruthenium(II),

osmium(II), and iridium(III), yielding important catalysts for the hydrogenation of polar double

bonds.

The ruthenium(II) complex, [Ru(p-cymene)(C–NH2)Cl]PF6 catalyzed the transfer and H2-

hydrogenation of ketones. The bifunctional hydride complex, [Ru(p-cymene)(C–NH2)H]PF6,

which contains a Ru–H/N–H couple showed no activity under catalytic conditions unless when

activated by a base. The outer-sphere mechanism involving bifunctional catalysis of ketone

reduction is disfavored according to experimental and theoretical studies and an inner-sphere

iiimechanism is proposed involving the decoordination of the amine donor from the C–NH2 ligand.

The ruthenium(II) complex [RuCp*(C–NH2)py]PF6 showed higher activity than the

iridium(III) complex [IrCp*(C–NH2)Cl]PF6 in the hydrogenation of ketones. This ruthenium(II)

complex also catalyzes the hydrogenation of an aromatic ester, a ketimine, and the

hydrogenolysis of styrene oxide. We proposed an alcohol-assisted outer sphere bifunctional

mechanism for both systems based on experimental findings and theoretical calculations. The

cationic iridium(III) hydride complex, [IrCp*(C–NH2)H]PF6 , was prepared and this failed to react

with a ketone in the absence of base. The crucial role of the alkoxide base was demonstrated in

the activation of this hydride complex in catalysis. Calculations support the proposal that the

base deprotonates the amine group of this hydride complex and triggers the migration of the

hydride to the η5-Cp* ring producing a neutral iridium(I) amido complex. This system contains an

active Ir–H/N–H couple required for the outer sphere hydrogenation of ketones in the

bifunctional mechanism.

ivAcknowledgements

I would like to thank first my supervisor, Professor Bob Morris. He is the kindest and the

most helpful person that I have ever met. At times he was busy with other duties in the

department, he could still come up with brilliant ideas to aid research, and spent quality times

with me for the betterment of my professional development. His encouragement can never be

forgotten.

Many thanks to all of the Morris group members, past and present. The joys and talks we

shared and the fruitful discussions we had are memorable and treasurable. They have made my

life in the lab “more interesting”, and a very enjoyable experience. Special thanks to the

undergraduate students Ali Rizvi and Hisashi Ohara for their dedicated efforts to this research

project.

More thanks go to the Department of Chemistry at the University of Toronto and all of the

supporting staff for their help for the past four years. In particular, I would like to thank Dr. Alan

Lough for his kind help and expertise in X-ray crystallography. He is a great person to work

with.

Last but not least, I would like to thank my family and all of my friends for the support, care

and love for my years at graduate studies, especially for the ups and downs that we went through

together.

I shall remember a quote from my chemistry teacher at high school, “ Chemistry = Chem Is

Try”. Indeed, this is very true!

vTable of Contents

Abstract

Acknowledgements

Table of Contents

List of Figures

List of Schemes

List of Tables

List of Abbreviations

Chapter 1: Introduction

1.1 Homogeneous Catalysis Involving Metal-Dihydrogen and Metal-Hydrides

Complexes

1.1.1 The Metal-Dihydrogen Bond.

1.1.2 The Acid-base Reactivity of Metal Hydride and Metal Dihydrogen

Complexes.

1.1.3 The Heterolytic Splitting of H2 at a Transition Metal Center and Implications

for Catalysis.

1.1.4 Metal Hydrides in Homogeneous Hydrogenation Reactions.

1.2 Mechanisms of the Hydrogenation of Polar Double Bonds

1.2.1 Ketone Hydrogenation, the Outer-sphere Mechanism and the “NH Effect”.

1.2.2 Effect of Alcohols on the Outer-sphere Bifunctional Mechanism using the

“NH Effect”.

1.2.3 Concerted or Stepwise Transfer of a Proton/Hydride Couple from the Metal

Center to the Polar Double bond.

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vi1.2.4 The Inner Sphere Mechanism.

1.3 Applications of Phosphines and N-Heterocyclic Carbenes in Catalysis

1.3.1 Applications of Phosphines in Catalysis.

1.3.2 N-heterocyclic carbenes and their Late Transition Metal Complexes.

1.3.3 Donor-functionalized N-heterocyclic carbenes and applications in catalysis.

1.4 Thesis Goals

Chapter 2: Synthesis and Characterization of Nitrile-Functionalized N-Heterocyclic

Carbenes and Their Complexes of Silver(I), Rhodium(I) and Ruthenium(II)

2.1 Abstract

2.2 Introduction

2.3 Results and Discussion

2.3.1 Synthesis of Imidazolium Salt Precursors.

2.3.2 Nitrile Functionalized N-Heterocyclic Carbene Complexes of Silver(I).

2.3.4. Hydrolysis of Nitrile groups on the Silver(I) Complex 2b.

2.3.5. Nitrile Functionalized N-Heterocyclic Carbene Complex of Rhodium(I) and

Ruthenium(II).

2.4 Conclusion

2.5 Experimental Section

2.5.1 General Considerations.

2.5.2. Synthesis of 1-(2-Cyanophenyl)-3-methylimidazolium Tetrafluoroborate

(1a).

2.5.3. Synthesis of 3-(Cyanomethyl)-1-(2-cyanophenyl)imidazolium

Hexafluorophosphate (1b).

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vii2.5.4. Synthesis of 1-(2-Cyanophenyl)-3-(2-pyridinylmethyl)imidazolium

Hexafluoro-phosphate (1c).

2.5.5. Synthesis of 1-(2-Cyanophenyl)-3-(2-pyridinyl)imidazolium

Hexafluorophosphate (1d).

2.5.6. Synthesis of 1-(2-Cyanophenyl)-3-(1-phenylethyl)imidazolium

Tetrafluoroborate (1e).

2.5.7. Synthesis of 1-(2-(Inden-3-yl)ethyl)-3-(2-cyanophenyl)imidazolium

Tetrafluoro-borate (1f).

2.5.8. Synthesis of Bis[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene]silver(I)

Tetrafluoroborate ([Ag(C–CN)2]BF4, 2a) .

2.5.9. Observation of Silver(I) Complex of (3-(Cyanomethyl)-1-(2-cyanophenyl)-

imidazol-2-ylidene (2b).

2.5.10. Observation of Silver(I) Complex of (3-(Carbomoylmethyl)-1-(2-

cyanophenyl)imidazol-2-ylidene (2e).

2.5.11. Synthesis of Bis{[1-(2-cyanophenyl)-3-(2-pyridinylmethyl)imidazol-2-

ylidene]silver(I)} Hexafluorophosphate (2c).

2.5.12. Synthesis of Bis{[1-(2-cyanophenyl)-3-(2-pyridinyl)imidazol-2-

ylidene]silver(I)} Hexafluorophosphate (2d).

2.5.13. Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-(η4-1,5-

cycloctadiene)rhodium(I)] Tetrafluoroborate ([Rh(C–CN)(cod)]2(BF4)2, 3).

2.5.14. Synthesis of Bis[chloro-(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-

(η6-p-cymene)ruthenium(II)] Tetrafluoroborate ([Ru(p-cymene)(C–CN)Cl]2(BF4)2,

4).

Chapter 3: Palladium(II) and Platinum(II) Complexes Featuring a Nitrile-Functionalized

N-Heterocyclic Carbene Ligand

3.1 Abstract

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viii3.2 Introduction


3.3.1 Transmetalation of a Nitrile-Functionalized N-heterocyclic Carbene Ligand

from Silver(I) to Palladium(II).

3.3.2 Hydrolysis of Nitrile-Functionalized N-Heterocyclic Carbene Ligands on

Palladium(II) Centers.

3.3.3 Palladium(II) Complex Bearing Nitrile-Functionalized N-Heterocyclic

Carbene (C–CN) and Methoxycyclooctenyl Ligands.

3.3.4 Nitrile-Functionalized N-Heterocyclic Carbene Complex of Platinum(II).

3.3.5 Nucleophilic Attack of Methoxide on the Coordinated 1,5-Cyclo-octadiene

Ligand of 7.

3.3.6 Proposed Reaction Pathways Leading to the Formation of Rotamers A and B

of Complexes 6, 8 and 9.

3.3.7 Platinum(II) Complex with Coordinated 1,3-bis(2,4,6-trimethylphenyl)-

imidazol-2-ylidene ligand (IMes).

3.4 Conclusion


3.5.1 General Considerations.

3.5.2 Synthesis of Bis(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-

palladium(II)(μ-dichloro)bis(acetonitrile)palladium(II) Tetrafluoroborate ([(C–

CN)2Pd(μ-Cl)2Pd(CH3CN)2](BF4)2, 5a).

3.5.3 Synthesis of (Acetonitrile)(1-(2-cyanophenyl)-3-methylimidzol-2-ylidene)

(η1:η2-2-methoxycyclooct-5-enyl)palladium(II) Tetrafluoroborate ([Pd(C–CN)

(η1:η2-coe-OMe)(CH3CN)]BF4, 6a).

3.5.4 Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-

methoxy-cyclooct-5-enyl)palladium(II)] Tetrafluoroborate ([Pd(C–CN)(η1:η2-coe-

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ixOMe)]2(BF4)2, 6b).

3.5.5 Synthesis of Chloro[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene](η4-1,5-

cyclooctadiene)platinum(II) Tetrafluoroborate ([Pt(C–CN)(cod)Cl]BF4, 7).

Hexafluorophosphate (1d).

3.5.6 Synthesis of Chloro[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-

2-methoxy-cyclooct-5-enyl)platinum(II) (Pt(C–CN)(η1:η2-coe-OMe)Cl, 8).

3.5.7 Synthesis of (Acetonitrile)(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)

(η1:η2-2-methoxycyclooct-5-enyl)platinum(II) Tetrafluoroborate ([Pt(C–CN)

(η1:η2-coe-OMe)(CH3CN)]BF4, 9a).

3.5.8 Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-

methoxy-cyclooct-5-enyl)platinum(II)] Tetrafluoroborate ([Pt(C–CN)(η1:η2-coe-

OMe)]2(BF4)2, 9b).

3.5.9 Synthesis of Chloro[1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene)](η4-

1,5-cyclo-octadiene)platinum(II) Tetrafluoroborate ([Pt(IMes)(cod)Cl]BF4, 11).

Chapter 4: Transmetalation of a Primary Amino-Functionalized N-Heterocyclic Carbene

Ligand from an Axially Chiral Square-Planar Nickel(II) Complex to Ruthenium(II) and

Osmium(II) Catalysts for the Hydrogenation of Polar Bonds

4.1 Abstract

4.2 Introduction


4.3.1 Reduction of a Nitrile-Functionalized Imidazolium Salt to the First

Homoleptic Primary Amino-Functionalized N-Heterocyclic Carbene Complex of

Nickel(II).

4.3.2 Solution NMR Studies of the Axial Chirality of the Homoleptic Primary

Amino-Functionalized N-Heterocyclic Carbene Complex of Nickel(II).

4.3.3 Transmetalation Reaction of a Primary Amino-Functionalized N-

Heterocyclic Carbene from Nickel(II) to Ruthenium(II) and Osmium(II)

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xComplexes with an Arene ligand.

4.3.4 Synthesis of a Ruthenium(II) Complex with a Primary Amino-

Functionalized N-Heterocyclic Carbene and Pentamethylcyclopentadienyl ligands.

4.3.5 The Transfer Hydrogenation of Acetophenone Catalyzed by Complexes 12,

13 and 14.

4.3.6 The H2-Hydrogenation of Ketones Catalyzed by Complexes 15 and 16.

4.3.7 The H2-Hydrogenation of Other Polar Bonds Catalyzed by Complex 15.

4.4 Conclusion


4.5.1 Synthesis.

4.5.2 Synthesis of Bis[1-(2-aminomethylphenyl)-3-methylimidazol-2-ylidene]-

nickel(II) Hexafluorophosphate ([Ni(C–NH2)2](PF6)2, 12).

4.5.3 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene]-

chloro(η6-p-cymene)ruthenium(II) Hexafluorophosphate ([Ru(p-cymene)(C–

NH2)Cl]PF6, 13).

4.5.4 Synthesis of [1-(2-(Aminomethyl)phenyl)-3-methylimidazol-2-ylidene]-

chloro(η6-p-cymene)osmium(II) Hexafluorophosphate ([Os(p-cymene)(C–

NH2)Cl]PF6, 14).

4.5.5 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene](η5-

pentamethyl-cyclopentadienyl)(pyridine)ruthenium(II) Hexafluorophosphate

([RuCp*(C–NH2)(py)]PF6, 15).

4.5.6 Synthesis of [2-(Diphenylphosphino)benzylamine](η5-pentamethyl-

cyclopentadienyl)(pyridine)ruthenium(II) Hexafluorophosphate ([RuCp*(P–NH2)

(py)]PF6, 16a).

4.5.7 Catalysis.

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xi4.5.8 General Procedure for Transfer Hydrogenation Studies.

4.5.9 General Procedure for H2-Hydrogenation Studies.

Chapter 5: Mechanistic Investigation of the Hydrogenation of Ketones Catalyzed by a

Ruthenium(II) Complex Featuring an N-Heterocyclic Carbene with a Tethered Primary

Amine Donor: Evidence for an Inner Sphere Mechanism

5.1 Abstract

5.2 Introduction


5.3.1 H2-Hydrogenation of Acetophenone Catalyzed by Complex 13.

5.3.2 H2-Hydrogenation of Other Ketones Catalyzed by Complex 13.

5.3.3 Kinetic Studies.

5.3.4 Effect of the Base on Catalysis.

5.3.5 Effect of Alcohols on Catalysis.

5.3.6 Isotope Effects and Deuterium Labelling Studies.

5.3.7 The Disfavored Outer-Sphere Bifunctional Mechanism.

5.3.8 The Favored Inner-Sphere Mechanism.

5.3.9 Theoretical Considerations: The Outer-sphere Bifunctional Mechanism.

5.3.10 Theoretical Considerations: The Inner-sphere Mechanism.

5.3.11 Possible Mechanism for Transfer Hydrogenation.

5.3.12 Role of Complex 17 in Catalysis.

5.4 Conclusion


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xii5.5.1 Synthesis.

5.5.2 Synthesis of [1-(2-(Aminomethyl)phenyl)-3-methylimidazol-2-ylidene]-

hydrido(η6-p-cymene)ruthenium(II) Hexafluorophosphate ([Ru(p-cymene)(C–

NH2)H]PF6, 17).

5.5.3 Synthesis of [1-(N,N-Dimethylaminopropyl)-3-methylimidazol-2-

ylidene]chloro(η6-p-cymene)ruthenium(II) Hexafluorophosphate Dimethyl

Sulfoxide Solvate ([Ru(p-cymene)(C–NMe2)Cl]PF6·1.5 DMSO, 18).

5.5.4 Catalysis.

5.5.5 Kinetics.

5.5.6 Kinetic Isotope Effect Studies.

5.5.7 Computational Details.

Chapter 6: Conventional Bifunctional Mechanism for Ketone Hydrogenation Catalyzed

by Structurally Similar Ruthenium and Iridium Complexes but with Unconventional

Intermediates for Iridium

6.1 Abstract

6.2 Introduction


6.3.1 Synthesis of Ruthenium(II) and Iridium(III) Complexes Containing a C–NH2

Ligand.

6.3.2 Synthesis, Observation, and Reactivity of Hydride Complexes of

Ruthenium(II) and Iridium(III).

6.3.3 Synthesis of an Iridium(III) Complex Containing a C–NMe2 Ligand.

6.3.4 General Features of the H2-Hydrogenation of Ketones Catalyzed by

Complexes 15, 19, 20 and 21.

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xiii6.3.5 Effect of Alkoxide Base on the H2-Hydrogenation of Acetophenone

Catalyzed by Complex 19.

6.3.6 The Importance of the NH2 Group in the Iridium(III) System on its Activity

in the Catalytic Hydrogenation of Ketones.

6.3.7 Selectivity in the Hydrogenation of an α,β-unsaturated ketone Catalyzed by

Complexes 15 and 19.

6.3.8 Effect of Alcohol and Other Additives on the H2-Hydrogenation of

Acetophenone Catalyzed by the Ruthenium(II) Complex 15.

6.3.9 Deuterium Labelling Studies Using the Ruthenium(II) Complex 15.

6.3.10 Effect of Alcohol on the H2-Hydrogenation of Acetophenone Catalyzed by

Iridium(III) Complexes 19 and 21.

6.3.11 Deuterium Labelling Studies Using the Iridium(III) Complex 19.

6.3.12 Stoichiometric Reactions Using Complex 19.

6.3.13 The Conventional Non-Alcohol Assisted Outer Sphere Bifunctional

Mechanism.

6.3.14 The Alcohol-Assisted Outer Sphere Bifunctional Mechanism for the

Ruthenium(II) System.

6.3.15 The Alcohol-Assisted Outer Sphere Bifunctional Mechanism Involving

Iridium(I) Intermediates.

6.3.16 Disfavored Inner Sphere Mechanisms Involving Cationic Iridium(III)

Intermediates.

6.3.17 Electronic Properties of Ruthenium(II) Complexes that Relate to their

Reactivity in Catalytic Hydrogenation.

6.4 Conclusion


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xiv6.5.1 Synthesis.


chloro-(η5-pentamethylcyclopentadienyl)iridium(III) Hexafluorophosphate

([IrCp*(C–NH2)Cl]PF6, 19).

6.5.3 Synthesis of [2-(Diphenylphosphino)benzylamine]-chloro-(η5-pentamethyl-

cyclopentadienyl)iridium(III) Hexafluorophosphate ([IrCp*(P–NH2)Cl]PF6, 20).


hydrido-(η5-pentamethylcyclopentadienyl)iridium(III) Hexafluorophosphate

([IrCp*(C–NH2)H]PF6, 21).

6.5.5 Synthesis of [1-(N,N-Dimethylaminopropyl)-3-methylimidazol-2-ylidene]-

chloro-(η5-pentamethylcyclopentadienyl)iridium(III) Hexafluorophosphate

([IrCp*(C–NMe2)Cl]PF6, 22).


carbonyl-(η5-pentamethylcyclopentadienyl)ruthenium(II) Hexafluorophosphate

([RuCp*(C–NH2) (CO)]PF6, 23).

6.5.7 Synthesis of [2-(Diphenylphosphino)benzylamine]-carbonyl-(η5-

pentamethylcyclopentadienyl)ruthenium(II) Hexafluorophosphate ([RuCp*(P–

NH2)(CO)]PF6, 24).

6.5.8 Representative Stoichiometric Reaction Using High Pressure of H2.

6.5.9 Stoichiometric Reaction Using 19 and 1-Phenylethoxide.

6.5.10 Catalysis.

6.5.11 Computational Details.

Chapter 7: Conclusions and Future Work

7.1 Conclusions

7.2 Future Work

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xvAppendix

Derivation of the Rate Law (eq 5.1, Chapter 5)

Complete Citation for Gaussian 03 and 09 Packages

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xviList of Figures

Figure 1.1. Bonding scheme of the η2-H2 ligand on a transition metal center.

Figure 1.2. Reversible proton exchange of a η2-H2 ligand with a pendant amine arm in a

ruthenium(II) complex containing a diphosphine ligand.

Figure 1.3. The catalytic hydrogenation of iminium cations (above) and quinolines

(below) catalyzed by ruthenium(II) and iridium(III) catalysts involving an [M](η2-H2)

intermediate (M = Ru or Ir).

Figure 1.4. Examples of ruthenium(II) complexes with hydride-amine or an amido group

that catalyze the hydrogenation of ketones under base free conditions.

Figure 1.5. The transition state of the alcohol-assisted heterolytic splitting of H2 calculated

by Andersson and co-workers using computational methods.

Figure 1.6. Concerted transfer of a proton/hydride couple from the Shvo's type catalyst to

benzaldehyde.

Figure 1.7. Orbital interaction diagram showing the hydride attack on a σ-bonded ketone.

Figure 1.8. The production of an (S)-N-alkylated aniline (NAA) using an iridium complex

containing a JOSIPHOS ligand as a catalyst.

Figure 1.9. Schematics showing the mesomeric effect to the electronic configuration and

the interactions of π-orbitals in the acyclic, bent singlet carbene N–C–N.

Figure 1.10. The structures of Bertrand's and Arduengo's carbenes.

Figure 1.11. Examples of late transition metal complexes and their use in (a) the oxidation

of alcohols, (b) the hydrosilylation of a terminal alkyne, and in (c) the carboxylation of

aromatic and heteroaromatic C–H bonds (from top to bottom).

Figure 1.12. Structures of some metal complexes containing an amino (NH)-

functionalized NHC ligand.

Figure 2.1. Nitrile-functionalized imidazolium salts 1a-1f.

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xviiFigure 2.2. Nitrile-functionalized N-heterocyclic carbene (C–CN) complexes of

palladium(II) (left) and nickel(II) (right).

Figure 2.3. ORTEP diagram of 1a depicted with thermal ellipsoids at 30% probability. The

counteranion and hydrogens have been omitted for clarity. Selected bond distances (Å) and

bond angles (deg): C(1)-N(1), 1.340(3); C(1)-N(2), 1.324(3); C(2)-C(3), 1.342(3); C(11)-

N(3), 1.139(3); N(1)-C(1)-N(2), 108.2(2).

Figure 2.4. ORTEP diagram of 1b depicted with thermal ellipsoids at 30% probability. The


bond angles (deg): C(1)-N(1), 1.342(5); C(1)-N(2), 1.328(5); C(2)-C(3), 1.349(6); C(12)-

N(4), 1.134(6); C(5)-N(3), 1.142(6); N(1)-C(1)-N(2), 107.8(4).



bond angles (deg): Ag(1)-C(1), 2.094(5); Ag(1)-C(4), 2.095(5); C(1)-N(1), 1.359(6); C(1)-

N(2), 1.362(6); C(13)-N(5), 1.140(7); C(1)-Ag(1)-C(4), 171.1(2); N(1)-C(1)-N(2),

104.4(4).

Figure 2.6. Proposed structures of Ag(I) complexes 2c and 2d forming 12- and 10

membered rings, respectively.

Figure 2.7. 1H NMR spectra (400 MHz) in the amide-NH region of (a) acetamide, (b)

acetamide prepared from hydrolysis of acetonitrile with silver oxide and water, and (c) 2e

in acetonitrile-d3.

Figure 2.8. ORTEP diagram of 3 depicted with thermal ellipsoids at 30% probability. The

counteranions and hydrogens have been omitted for clarity. Selected bond distances (Å)

and bond angles (deg): Rh(1)-C(16), 2.040(5); Rh(1)-N(1), 2.064(4); Rh(1)-cod(trans to

N)cent, 2.016; Rh(1)-cod(trans to C)cent, 2.100; C(9)-N(1), 1.139(6); C(9)-N(1)-Rh(1),

172.0(5); C(16)-Rh(1)-N(1), 89.9(2); N(1)-Rh(1)-cod(trans to N)avg, 160.6; N(1)-Rh(1)-

cod(cis to N)avg, 91.15; C(16)-Rh(1)-cod(trans to C)avg, 162.1; C(16)-Rh(1)-cod(cis to

C)avg, 92.37.


counteranions and hydrogens have been omitted for clarity. Only one asymmetric unit is

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xviiishown. Selected bond distances (Å) and bond angles (deg): Ru(1a)-C(1a), 2.078(7);

Ru(1a)-N(3a), 2.028(8); Ru(1a)-Cl(1a), 2.408(2); Ru(1a)-C(12a), 2.238(8); C(11a)-N(3a),

1.13(1); C(11a)-N(3a)-Ru(1a), 173.3(6); C(1a)-Ru(1a)-N(3a), 84.9(3); C(1a)-Ru(1a)-

Cl(1a), 90.9(2); N(3a)-Ru(1a)-Cl(1a), 83.7(2).

Figure 3.1. Nitrile-functionalized N-heterocyclic carbene complexes of Ag(I) and Rh(I)

and the general structures of the complexes reported in this chapter (M = Pd(II), Pt(II); D =

olefin or alkyl ligand; L = nitrile donor or a chloro group).

Figure 3.2. ORTEP diagram of 5b⋅1.5 CH3CN depicted with thermal ellipsoids at the 30%

probability level. The counteranions, hydrogens, and solvent molecules have been omitted

for clarity. Selected bond distances (Å) and bond angles (deg): Pd(1)-C(1), 1.969(6);

Pd(3)-C(20), 1.957(6); Pd(1)-N(3), 2.015(5); Pd(3)-N(4), 2.018(5); Pd(2)-N(3), 1.976(5);

Pd(2)-N(4), 1.972(5); Pd(1)-N(8), 2.094(6); Pd(1)-N(7), 2.020(5); C(10)-N(3), 1.272(8);

C(11)-N(4), 1.265(8); C(10)-O(1), 1.361(7); C(11)-O(1), 1.382(7); N(3)-Pd(2)-N(4),

91.9(2); C(1)-Pd(1)-N(3), 85.4(2); C(10)-O(1)-C(11), 126.7(5); C(10)-N(3)-Pd(2),

125.3(4).

Figure 3.3. Diastereomers and rotamers (A and B) of Pd(II) (6a) and Pt(II) (9a) complexes

bearing 2-methoxycyclooct-5-enyl and the C–CN ligands.

Figure 3.4. ORTEP diagram of 6a depicted with thermal ellipsoids at the 30% probability

level. The counteranion and hydrogens have been omitted for clarity. Selected bond

distances (Å) and bond angles (deg): Pd(1)-C(1), 2.012(4); Pd(1)-C(19), 2.040(4); Pd(1)-

N(4), 2.164(3); Pd(1)-coe(trans to C)cent, 2.161; C(11)-N(3), 1.148(6); C(18)-O(1),

1.441(5); C(1)-Pd(1)-coe(trans to C)avg, 161.2; C(19)-Pd(1)-N(4), 177.2(9); C(1)-Pd(1)-

C(19), 87.7(1).

Figure 3.5. ORTEP diagram of 7 depicted with thermal ellipsoids at the 30% probability

level. The counteranion and hydrogens have been omitted for clarity. Selected bond

distances (Å) and bond angles (deg): Pt(1)-C(1), 2.011(5); Pt(1)-Cl(1), 2.317(6); Pt(1)-

cod(trans to C)cent, 2.152; Pt(1)-cod(cis to C)cent, 2.048; C(11)-N(3), 1.134(7); C(1)-Pt-(1)-

cod(trans to C)avg, 162.3; Cl(1)-Pt(1)-cod(cis to C)avg, 161.0; C(1)-Pt(1)-cod(cis to C)avg,

94.0.

Figure 3.6. ORTEP diagrams of 8 (left) and 9a (right) depicted with thermal ellipsoids at

39

51

54

56

57

61

xixthe 30% probability level. The counteranion and hydrogens have been omitted for clarity.

Selected bond distances (Å) and bond angles (deg): 8 (left): Pt(1)-C(1), 1.969(1); Pt(1)-

C(12), 2.095(1); Pt(1)-Cl(1), 2.430(4); Pt(1)-coe(trans to C)cent, 2.102; C(11)-N(3),

1.135(7); C(19)-O(1), 1.418(2); C-(1)-Pt(1)-coe(trans to C)avg, 160.7; C(12)-Pt(1)-Cl(1),

178.4(4); C(1)-Pt(1)-C(12), 88.9(5). 9a (right): Pt(1)-C(1), 2.001(5); Pt(1)-C(17), 2.044(5);

Pt(1)-N(4), 2.122(5); Pt(1)-coe(trans to C)cent, 2.100; C(10)-N(3), 1.145(8); C(16)-O(1),

1.449(6); C(1)-Pt(1)-coe(trans to C)avg, 161.0; C(17)-Pt(1)-N(4), 178.3(0); C-(1)-Pt(1)-

C(17), 88.9(7).

Figure 3.7. ORTEP diagram of 11⋅0.5 CH2Cl2 depicted with thermal ellipsoids at the 30%

probability level. The counteranion, hydrogens, and solvent molecules have been omitted

for clarity. Only one asymmetric unit is shown. Selected bond distances (Å) and bond

angles (deg): Pt(1A)-C(1A), 2.037(1); Pt(1A)-Cl(1A), 2.315(3); Pt(1A)-cod(trans to C)cent,

2.173; Pt(1A)-cod(cis to C)cent, 2.084; C(1A)-Pt(1A)-cod(trans to C)avg, 162.3; Cl(1)-Pt(1)-

cod(cis to C)avg, 160.9; C(1)-Pt(1)-cod(cis to C)avg, 95.1.

Figure 4.1. Examples of transition metal complexes bearing amino-functionalized N-

heterocyclic carbene ligands reported by Douthwaite and Oro. See references 9a, 9b and

9e.


counteranions and most of the hydrogens have been omitted for clarity. Selected bond

distances (A° ) and bond angles (deg): Ni(1)-C(1), 1.870(6); Ni(1)-C(12), 1.883(6); Ni(1)-

N(5), 1.963(5); Ni(1)-N(6), 1.937(5); C(1)-Ni(1)-N(5), 91.8(3); C(1)-Ni(1)-C(12), 88.1(3).

Figure 4.3. Selected sections of the 1H NMR spectra of complex 12 in acetonitrile-d3 (400

MHz, 298 K) and the assignments of the imidazolylidene ring (left) and methyl protons

(right) in the presence of (a) 0 equiv, (b) 1 equiv, (c) 2 equiv, and (d) 3 equiv of [Bu4N][Δ-

TRISPHAT].

Figure 4.4. ORTEP diagram of 13⋅THF depicted with thermal ellipsoids at 30%

probability. The counteranion, solvent molecule, and most of the hydrogens have been

omitted for clarity. Selected bond distances (Å) and bond angles (deg): Ru(1)-C(1),

2.092(5); Ru(1)-N(3), 2.146(4); Ru(1)-Cl(1), 2.4180(13); Ru(1)-C(15), 2.248(5); C(1)-

Ru(1)-N(3), 91.98(17); C(1)-Ru(1)-Cl(1), 88.24(13); Cl(1)-Ru(1)-N(3), 81.81(11).

63

68

79

81

83

85

xxFigure 4.5. ORTEP diagram of 14 depicted with thermal ellipsoids at the 30% probability

level. The counteranion and most of the hydrogens have been omitted for clarity. Selected

bond distances (Å) and bond angles (deg): Os(1)-C(1), 2.07(1); Os(1)-N(3), 2.137(9);

Os(1)-Cl(1), 2.422(3); Os(1)-C(15), 2.201(6); C(1)-Os(1)-N(3), 91.1(4); C(1)-Os(1)-Cl(1),

87.5(3); Cl(1)-Os(1)-N(3), 80.0(3).

Figure 4.6. Selected sections of the 1H NMR spectra of complex 13 in dichloromethane-d2

(400 MHz, 298 K) and the assignments of the imidazolylidene ring (left), p-cymene ring

(middle) and the isopropyl-methyl protons (right) in the presence of (a) 0 equiv, (b) 1

equiv, (c) 2 equiv, and (d) 3 equiv of [Bu4N][Δ-TRISPHAT].


counteranions and most of the hydrogens have been omitted for clarity. Only one

asymmetric unit is shown. Selected bond distances (Å) and bond angles (deg): Ru(1a)-

C(1a), 2.03(1); Ru(1a)-N(3a), 2.195(7); Ru(1a)-N(4a), 2.156(8); Ru(1a)-C(14a), 2.215(9);

C(1a)-Ru(1a)-N(3a), 91.9(3); N(3a)-Ru(1a)-N(4a), 90.9(4); C(1a)-Ru(1a)-N(3a), 81.3(3).

Figure 4.8. ORTEP diagram of 16a depicted with thermal ellipsoids at 30% probability.

The counteranions and most of the hydrogens have been omitted for clarity. Selected bond

distances (Å) and bond angles (deg): Ru(1)-P(1), 2.314(1); Ru(1)-N(1), 2.188(2); Ru(1)-

N(2), 2.171(2); Ru(1)-C(8), 2.207(3); P(1)-Ru(1)-N(1), 84.89(7); N(1)-Ru(1)-N(2),

87.35(9); P(1)-Ru(1)-N(2), 95.72(7).

Figure 4.9. Catalytic transfer hydrogenation of acetophenone to 1-phenylethanol in the

presence of 13, potassium tert-butoxide, and 2-propanol (6 mL) at 75°C (C/B/S = 1/8/200).

The conversions from two runs and an average of these are shown.

Figure 4.10. Addition of acetophenone (200 mg, C/S = 1/200) after 180 min of transfer

hydrogenation of acetophenone in the presence of 13, potassium tert-butoxide, and 2-

propanol (6 mL) at 75°C (C/B/S = 1/8/200).

Figure 4.11. Catalytic H2-hydrogenation of 4'-bromoacetophenone to 1-(4'-

bromophenyl)ethanol (Table 4.3, entry 4) in the presence of catalyst 15, KOtBu, and THF

(6 mL) in 8 bar of H2 pressure at 25°C (C/B/S = 1/8/1500).The concentrations of the

product alcohol from two runs and an average of these are shown.

86

88

90

90

91

92

96

xxiFigure 4.12. Catalytic H2-hydrogenation of 4'-chloroacetophenone to 1-(4'-chlorophenyl)-

ethanol in the presence of catalyst 15, KOtBu, and THF (6 mL) in 8 bar of H2 at 25°C

(C/B/S = 1/14/2250). Mercury poisoning test was conducted by adding a drop of mercury

to the reaction mixture against a flow of hydrogen at 15 min.

Figure 5.1. Transfer hydrogenation of acetophenone catalyzed by complex 13 in basic 2-

propanol.

Figure 5.2. Catalytic H2-hydrogenation of benzophenone to benzhydrol (Table 5.2, entries

2 and 3) in the presence of catalyst 13, KOtBu, and THF (6 mL) in 25 bar of H2 pressure at

50°C with a C/B/S ratio of (a) 1/8/200 (triangles) and (b) 1/8/400 (squares).

Figure 5.3. Kinetic data showing the production of 1-phenylethanol from acetophenone

catalyzed by complex 13 in basic THF: (a) dependence on the catalyst concentration (13);

(b) dependence on the hydrogen concentration; (c) dependence on the acetophenone

concentration; (d) dependence on the base concentration (KOtBu); (e) dependence on the

1-phenylethanol concentration. The inset shows the dependence of initial rates (v0, 10-5 M

s-1) and the concentration of the analyte of interest.

Figure 5.4. Linear plot showing the relationship between the reciprocal of the initial rate

(1/v0 in 103 M-1 s) and acetophenone concentration (M). The rate (kH) and equilibrium (Keq)

constants were derived from the slope and the y intercept according to eq 5.2, respectively.


catalyzed by complex 13 in basic THF: (a) under 8 bar of D2 gas with different

concentrations of acetophenone; (b) under 25 bar of H2 gas with different concentrations of

acetophenone-d3.

Figure 5.6. Linear plots showing the relationship between the reciprocal of the initial rate

(1/v0 in 103 M-1 s) and acetophenone concentration (M), using (a) D2 gas (8 bar) and

acetophenone, (b) H2 gas (25 bar) and acetophenone, and (c) H2 gas (25 bar) and

acetophenone-d3 (0.16 – 0.49 M), in the production of 1-phenylethanol from acetophenone

catalyzed by complex 13 in basic THF.

Figure 5.7. ORTEP diagram of 17⋅THF depicted with thermal ellipsoids at the 30%

probability level. The counteranion, solvent molecule, and most of the hydrogens have

97

109

113

115

119

122

123

xxiibeen omitted for clarity. Selected bond distances (Å) and bond angles (deg): Ru(1)-C(1),

2.029(7); Ru-(1)-N(3), 2.145(5); Ru(1)-H(1ru), 1.79(7); Ru(1)-C(15), 2.232(6); C(1)-

Ru(1)-N(3), 91.9(2); C(1)-Ru(1)-H(1ru), 81(2); H(1ru)-Ru(1)-N(3), 84(2).

Figure 5.8. Reaction profiles showing the hydrogenation of acetophenone catalyzed by

complex 13 (blue squares) and complex 17 (red circles) in (a) basic THF at 25 bar of H2

pressure and 50°C and (b) 2-propanol at 75°C. The C/B/S ratio was 1/8/200. The transfer

hydrogenation of acetophenone catalyzed by complex 13 in basic 2-propanol was

described in Chapter 4.

Figure 5.9. Reaction profile showing the hydrogenation of trans-4-phenyl-but-3-en-2-one

catalyzed by complex 13 in basic THF at 25 bar of H2 pressure and 50°C: (blue circles)

trans-4-phenylbut-3-en-2-ol; (red squares) 4-phenylbutan-2-ol; (green triangles) 4-

phenylbutan-2-one. The C/B/S ratio was 1/8/200.

Figure 5.10. Possible reaction intermediates for the inner-sphere mechanism involving

hydride migration to the coordinated ketone substrate: (left) decoordination of the

chelating amine group from the NHC ligand; (right) ring slippage of the arene ring.

Figure 5.11. Catalytic H2-hydrogenation of acetophenone to 1-phenylethanol in the

presence of catalyst, KOtBu, and THF (6 mL) in 25 bar of H2 pressure at 50°C with a

C/B/S ratio of (a) 1/8/200 (red squares), catalyst 13, [13] = 0.83 mM and (b) 1/10/240,

catalyst 18, [18] = 0.71 mM (blue triangles).

Figure 5.12. The free energy profile for an outer-sphere mechanism for the H2-

hydrogenation of acetone starting from A1 and moving to the right and the enolate

formation starting from A1 and moving to the left. The gas phase free energies (1 atm, 298

K) are reported relative to G in kcal/mol.

Figure 5.13. Selected computed structures A-C and G for the outer-sphere mechanism in

the H2-hydrogenation of acetone and the transition state structures for the heterolytic

splitting of H2 (TSB,C) and for the concerted transfer of a hydride/proton pair to the ketone

(TSD,E). The bond lengths (Å) are given in the structures.

Figure 5.14. Computed structures and energies (at 298 K and 1 atm relative to G + H2 in

kcal/mol) for the ring slippage mechanism.

127

128

130

131

133

135

136

137

xxiiiFigure 5.15. The free energy profile for the inner-sphere mechanism in the H2-

hydrogenation of acetone starting from H and moving to the right. The amino group is

decoordinated throughout the catalytic cycle. Moving to the left from H leads to the

unstable enolate complex M. The gas phase free energies (1 atm, 298 K) are reported

relative to G, hydrogen and acetone in kcal/mol.

Figure 5.16. Selected computed structures H-K for the inner-sphere mechanism involving

decoordination of the amine group of the NHC ligand in the H2-hydrogenation of ketone

and the transition state structures for the heterolytic splitting for H2 (TSI,J) and for the

hydride attack on the coordinated ketone (TSK,H). The bond lengths (Å) are given in the

structures.

Figure 6.1. Late transition metal complexes containing a chelating N-heterocyclic carbene

(NHC)-primary amine (C–NH2) or a chelating phosphine-primary amine (P–NH2) ligand.

Figure 6.2. An inner sphere mechanism involving the decoordination of the primary amine

group proposed for the H2-hydrogenation of ketones catalyzed by complex 13 in the

presence of an alkoxide base.


counteranion and most of the hydrogens have been omitted for clarity. Selected bond

distances (Å) and bond angles (deg): Ir(1)–C(1), 2.067(7); Ir(1)–N(3), 2.127(5); Ir(1)–

Cl(1), 2.424(2); Ir(1)–C(13), 2.199(6); C(1)–Ir(1)–N(3), 90.9(2); C(1)–Ir(1)–Cl(1),

92.2(2); Cl(1)–Ir(1)–N(3), 80.7(1).

Figure 6.4. ORTEP diagram of 20 depicted with thermal ellipsoids at 30% probability.

The counteranion and most of the hydrogens have been omitted for clarity. Selected bond

distances (Å) and bond angles (deg): Ir(1)–P(1), 2.307(2); Ir(1)–N(1), 2.146(8); Ir(1)–

Cl(1), 2.407(2); Ir(1)–C(24), 2.208(9); P(1)–Ir(1)–N(1), 88.9(2); P(1)–Ir(1)–Cl(1),

89.02(9); Cl(1)–Ir(1)–N(1), 82.3(2).


The counteranion and most of the hydrogens have been omitted for clarity. The position of

the hydride ligand is not refined and thus not shown. Selected bond distances (Å) and bond

angles (deg): Ir(1)–C(1), 2.015(5); Ir(1)–N(3), 2.151(4); Ir(1)–C(14), 2.233(3); C(1)–Ir(1)–

N(3), 89.6(2).

138

140

154

155

158

159

161

xxivFigure 6.6. ORTEP diagram of 22 depicted with thermal ellipsoids at 30% probability.


distances (Å) and bond angles (deg): Ir(1)–C(1), 2.036(4); Ir(1)–N(3), 2.225(4); Ir(1)–

Cl(1), 2.426(1); Ir(1)–C(11), 2.264(4); C(1)–Ir(1)–N(3), 87.5(2); C(1)–Ir(1)–Cl(1),

95.0(1); Cl(1)–Ir(1)–N(3), 84.4(1).

Figure 6.7. Reaction profiles showing the effect of the concentrations of catalyst,

hydrogen and substrate to the H2-hydrogenation of benzophenone catalyzed by complex

19. (a) [19] = 0.72 mM, [benzophenone] = 0.14 M, P(H2) = 25 bar, red circles; (b) [19] =

0.72 mM, [benzophenone] = 0.14 M, P(H2) = 15 bar, blue diamonds; (c) [19] = 0.72 mM,

[benzophenone] = 0.29 M, P(H2) = 25 bar, green squares; (d) [19] = 1.2 mM,

[benzophenone] = 0.14 M, P(H2) = 25 bar, purple crosses. All of the reactions were

conducted in 25 bar H2 at 50°C in THF and KOtBu was used as a base (5.9 mM).

Figure 6.8. Reaction profiles showing the effect of alcohols and pyridine on the

hydrogenation of acetophenone catalyzed by complex 15 in (a) basic THF, red circles; (b)

basic 2-propanol, blue diamonds; (c) basic THF, [1-phenylethanol] = 0.2 M, green squares;

(d) basic THF, [1-phenylethanol] = 0.4 M, orange triangles; (e) basic THF, [pyridine] =

0.030 M, purple crosses. All of the reactions were conducted with 8 bar H2 at 25°C and

KOtBu was used as the base. The C/B/S ratio was 1/8/2515.

Figure 6.9. Reaction profiles showing the effect of the concentrations of catalyst,

hydrogen and substrate on the hydrogenation of acetophenone catalyzed by complex 15,

(a) [15] = 0.77 mM, [acetophenone] = 1.9 M, P(H2) = 8 bar, red circles; (b) [15] = 1.3 mM,

[acetophenone] = 1.9 M, P(H2) = 8 bar, blue squares; (c) [15] = 0.77 mM, [acetophenone]

= 0.97 M, P(H2) = 8 bar, green triangles; (d) [15] = 0.77 mM, [acetophenone] = 1.9 M,

P(H2) = 2 bar, orange crosses. All of the reactions were conducted with 25oC in THF and

KOtBu was used as the base (5.9 mM).

Figure 6.10. Reaction profiles showing the effect of alcohols on the H2-hydrogenation of

acetophenone catalyzed by the chloride complex 19 in the presence of KOtBu, in (a) basic

THF, red circles, C/B = 1/8; (b) basic 2-propanol, blue diamonds, C/B = 1/8; (c) basic

THF, [1-phenylethanol] = 0.015 M, C/B = 1/8, green squares; (d) basic 2-propanol, C/B =

1/16, purple triangles. All of the reactions were conducted using 25 bar H2 at 50°C. The

C/S ratio was 1/200.

163

164

170

170

172

xxvFigure 6.11. Reaction profiles showing the effect of alcohols on the H2-hydrogenation of

acetophenone catalyzed by the hydride-amine complex 21 in (a) basic 2-propanol, blue

diamonds; (b) basic THF, red squares; (c) basic 2-propanol, [1-phenylethanol] = 0.030 M,

green triangles. All of the reactions were conducted using 25 bar H2 at 50°C and KOtBu

was used as the base. The C/B/S ratio was 1/8/200.

Figure 6.12. The free energy profile for the outer sphere bifunctional mechanism in the H2-

hydrogenation of acetone starting from A and moving to the right. Pathway colored in blue

represents the ruthenium(II) system and the one in red represents the iridium(III) system.

The gas phase free energies (1 atm, 298 K) are reported relative to A, hydrogen and

acetone in kcal/mol.

Figure 6.13. Computed transition state structures for the heterolytic splitting of H2 (TSC,D)

of the ruthenium(II) (left) and the iridium(III) system (right). The bond lengths (Å) are

given in the structures. The color code for the atoms are: ruthenium (orange), iridium

(yellow), nitrogen (blue), carbon (grey) and hydrogen (white).

Figure 6.14. Computed transition state structures for the transfer of a proton/hydride pair

to acetone (TSE,F) from the ruthenium(II) (above) and iridium(III) hydrides (below). The

bond lengths (Å) are given in the structures. The color code for the atoms are: ruthenium

(orange), iridium (yellow), nitrogen (blue), oxygen (blue), carbon (grey) and hydrogen

(white).

Figure 6.15. The free energy profile for the outer sphere bifunctional mechanism in the

activation of H2 starting from A and moving to the right (blue pathway), and in the

presence of 2-propanol staring from Aalc and moving to the right (red pathway). The gas

phase free energies (1 atm, 298 K) are reported relative to A, hydrogen and acetone in

kcal/mol.

Figure 6.16. Computed transition state structure for the heterolytic splitting of H2 (TSC,Dalc)

by the ruthenium(II) system in the presence of 2-propanol. The bond lengths (Å) are given

in the structure. The color code for the atoms are: ruthenium (orange), nitrogen (blue),

oxygen (red), carbon (grey) and hydrogen (white).

Figure 6.17. Computed transition state structures for the non-alcohol assisted (TS(HI)3,4,

left) and the alcohol-assisted heterolytic splitting of H2 (TS(HI)3,4alc, right) by the

173

178

179

179

181

182

xxviiridium(I) system. The bond lengths (Å) are given in the structures. The color code for the

atoms are: iridium (yellow), nitrogen (blue), oxygen (red), carbon (grey) and hydrogen

(white).

Figure 6.18. The free energy profile for the (a) alcohol-assisted outer sphere bifunctional

mechanism (blue pathway) and (b) the non alcohol-assisted outer sphere bifunctional

mechanism (red pathway) in the H2-hydrogenation of acetone starting from the amido

complex HI1 and moving to the right. The gas phase free energies are reported relative to

HI1, hydrogen, acetone and 2-propanol for the blue pathway, and to HI1, hydrogen and

acetone for the red pathway, in kcal/mol.

Figure 6.19. Computed transition state structure for the attack of hydride on the

coordinated acetone (TSM,J) of the iridium(III) system for the inner sphere mechanism

involving the decoordination of the amine group. The bond lengths (Å) are given in the

structure. The colour code for the atoms are: iridium (yellow), nitrogen (blue), oxygen

(red), carbon (grey) and hydrogen (white).



distances (Å) and bond angles (deg): Ru(1)–C(1), 2.065(4); Ru(1)–N(3), 2.178(3); Ru(1)–

C(22), 1.859(4); Ru(1)–C(15), 2.223(4); C(22)–O(1), 1.149(5); C(1)–Ru(1)–N(3), 90.8(2);

C(1)–Ru(1)–C(22), 95.1(2); C(22)–Ru(1)–N(3), 91.7(2).



distances (Å) and bond angles (deg): Ru(1)–P(1), 2.320(1); Ru(1)–N(1), 2.166(4); Ru(1)–

C(30), 1.877(6); Ru(1)–C(24), 2.218(5); C(30)–O(1), 1.140(6); P(1)–Ru(1)–N(1), 87.3(1);

P(1)–Ru(1)–C(30), 88.6(2); C(30)–Ru(1)–N(1), 90.8(2).

Figure 6.22. The carbonyl stretching wavenumbers (cm-1 in KBr) of a series of

ruthenium(II) complexes, [RuCp*(D–NH2)CO]+, where D is a donor group.

Figure 7.1. The structures of ruthenium(II) complexes containing the C–NH2 ligand

forming a six-membered ring metal-chelate (-M–C–NH2-).

185

186

188

189

190

191

208

xxviiFigure 7.2. Proposed structure of an iron(II) complex containing a C–N–N–C type donor

ligand. 209

xxviiiList of Schemes

Scheme 1.1. The Proposed Mechanism for the Hydrogenation of Terminal Alkenes

Catalyzed by the Rhodium(I)-based Wilkinson's Catalyst.

Scheme 1.2. The Outer Sphere Bifunctional Mechanism Using the “NH effect” for the

Hydrogenation of Aromatic Ketones.

Scheme 1.3. The Inner Sphere Mechanism for the H2-Hydrogenation of Aromatic Ketones.

Scheme 2.1. Synthesis of the Imidazolium Salt 1a and its Ag(I), Rh(I) and Ru(II)

Complexes 2a, 3 and 4.

Scheme 2.2. Synthesis of Imidazolium Salt 1b and the Ag(I) complexes 2b and 2e.

Scheme 2.3. Synthesis of Imidazolium Salts 1c to 1f and the Ag(I) Complexes 2c and 2d.

Scheme 2.4. Proposed Reaction Pathways to Hydrolysis of Ag(I) Complex 2b to 2e.

Scheme 3.1. Synthesis of Pd(II) and Pt(II) Complexes (5, 6a, and 7) Starting from a

Nitrile- Functionalized N-Heterocyclic Carbene Complex of Ag(I) (2a).

Scheme 3.2. Interconversion of 6a to 6b and 9a to 9b in Different Recrystallization

Solvents.

Scheme 3.3. Nucleophilic Attack of Methoxide at the Coordinated Cyclooctadiene Ligand

of 7 to 8 and Chloride Abstraction of 8 with AgBF4 in CH3CN to 9a.

Scheme 3.4. Proposed Reaction Pathways Leading to the Formation of Rotamers A and B

of Complexes 6, 8, and 9.

Scheme 3.5. Synthesis of Pt(II) Complex 11 from an N-Heterocyclic Carbene Complex of

Ag(I) (10).

Scheme 4.1. Synthesis of a Homoleptic Primary Amino-Functionalized N-Heterocyclic

Carbene Complex of Nickel(II) (12).

Scheme 4.2. Synthesis of Complexes 13 and 14 Bearing the C–NH2 Ligand by the

Transmetalation Reaction Involving Complex 12 and [M(p-cymene)Cl2]2 (M = Ru, Os).

6

8

12

28

28

29

37

52

58

62

66

67

80

84

xxixScheme 4.3. Synthesis of the Ruthenium(II) Complexes Containing the C–NH2 (15) and

P–NH2 (l6a) Ligands.

Scheme 5.1. Reaction Scheme Showing the Definitions of the Rate and Equilibrium

Constants.

Scheme 5.2. Possible Outer-Sphere Mechanism That Involves Bifunctional Catalysis in the

Hydrogenation of Acetophenone.

Scheme 5.3. Synthesis of Complex 17 from Reaction of Complex 13 and Basic 2-

Propanol.

Scheme 5.4. Hydrogenation of trans-4-Phenyl-but-3-en-2-one Catalyzed by Complex 13.

Scheme 5.5. Synthesis of Complex 18 by in Situ Generation of the Silver(I) Carbene

Complex and Subsequent Transmetalation of the NHC Ligand to Ruthenium(II).

Scheme 5.6. Proposed Mechanism for the H2-Hydrogenation of Ketones Catalyzed by

Complex 13 and an Alkoxide Base.

Scheme 6.1. An Alcohol-assisted Outer Sphere Bifunctional Mechanism of H2-

Hydrogenation of Ketones Catalyzed by Ruthenium(II) and Iridium(I) Systems Containing

a C–NH2 Ligand.

Scheme 6.2. Synthesis of Iridium(III) and Ruthenium(II) Complexes Containing a C–NH2

Ligand.

Scheme 6.3. Synthesis of Iridium(III) and Ruthenium(II) Complexes Containing a P–NH2

Ligand.

Scheme 6.4. Synthesis of a Iridium(III) Complex Containing a C–NMe2 ligand.

Scheme 6.5. The Hydrogenation of trans-4-Phenyl-but-3-ene-2-one Catalyzed by

Complexes 15 and 19.a

Scheme 6.6. Computed Outer Sphere Bifunctional Mechanism in the Hydrogenation of

Acetone Catalyzed by Complexes of Ruthenium(II) and Iridium(III).

Scheme 6.7. Computed Reaction Pathways of the Activation of H2 by Complex A in the

89

117

125

126

129

132

144

156

157

158

162

169

177

xxxPresence of 2-Propanol.

Scheme 6.8. Computed Hydride Migration Pathway from the Ir–H bond to the

Coordinated Cp Ligand Starting from R.

Scheme 6.9. Computed Alcohol-assisted Outer Sphere Bifunctional Mechanism in the H2-

Hydrogenation of Acetone Catalyzed by Complexes of Iridium(I).

Scheme 6.10. The Disfavoured Pathways Involving Either an η5 to η3 Ring Slip or a

Decoordination of the Amine Group Leading to the Activation of H2 by the Iridium(III)

System.

180

183

184

187

xxxiList of Tables

Table 4.1. The transfer hydrogenation of acetophenone to 1-phenylethanol in basic 2-

propanol catalyzed by complexes 12, 13 and 14.

Table 4.2. The hydrogenation of acetophenone catalyzed by complex 15 in the presence of

KOtBu.a

Table 4.3. The hydrogenation of substituted acetophenones catalyzed by complex 15 in the

presence of KOtBu.a

Table 4.4. The hydrogenation of organic molecules with polar bonds catalyzed by complex

15 in the presence of KOtBu.a

Table 5.1. H2-Hydrogenation of Acetophenone to 1-Phenylethanol Catalyzed by Complex

13.

Table 5.2. H2-Hydrogenation of Ketones Catalyzed by Complex 13.

Table 5.3. Kinetic Data for the Hydrogenation of Acetophenone Catalyzed by Complex 13.

Table 5.4. Kinetic Data for Kinetic Isotope Effect Studies of the Hydrogenation of

Acetophenone Catalyzed by Complex 13.

Table 5.5. Isotope Effect for the Hydrogenation of Acetophenone Catalyzed by Complex

13.

Table 5.6. Atomic Polar Tensor (APT) Charges (in ESU) on Selected Atoms for the

Computed Structures A-C, G, TSB,C, and TSD,E.

Table 5.7. Atomic Polar Tensor (APT) Charges (in ESU) on Selected Atoms for the

Computed Structures H-K, TSI,J and TSK,H.

Table 6.1. The H2-Hydrogenation of Acetophenone Catalyzed by Iridium(III) Complexes.

Table 6.2. The H2-Hydrogenation of Benzophenone Catalyzed by Iridium(III) Complexes.

Table 6.3. Transfer Hydrogenation of Acetophenone Catalyzed by Iridium(III)

Complexes.

93

94

95

98

111

112

118

124

124

137

141

165

166

166

xxxiiTable 6.4. Deuteration of Acetophenone and 2-Propanol Catalyzed by Complex 15.

Table 6.5. Deuteration of Acetophenone and 1-phenylethanol Catalyzed by Complex 19.

Table A.1. The oven temperatures, retention times (tR, tp, /min) for all of the substrates and

alcohol products reported from GC analyses.

171

174

210

xxxiiiList of Abbreviations

1a

1b

1c

1d

1e

1f

2a

2b

2c

2d

2e

3

4

5a

1-(2-cyanophenyl)-3-methylimidazolium tetrafluoroborate

3-(cyanomethyl)-1-(2-cyanophenyl)imidazolium

hexafluorophosphate

1-(2-cyanophenyl)-3-(2-pyridinylmethyl)imidazolium

hexafluorophosphate

1-(2-cyanophenyl)-3-(2-pyridinyl)imidazolium

hexafluorophosphate

1-(2-cyanophenyl)-3-(1-phenylethyl)imidazolium

tetrafluoroborate

1-(2-(inden-3-yl)ethyl)-3-(2-cyanophenyl)imidazolium

tetrafluoroborate

[Ag(C–CN)2]BF4

silver(I) complex of (3-(cyanomethyl)-1-(2-cyanophenyl)-

imidazol-2-ylidene

bis{[1-(2-cyanophenyl)-3-(2-pyridinylmethyl)imidazol-2-

ylidene]silver(I)} hexafluorophosphate

bis{[1-(2-cyanophenyl)-3-(2-pyridinyl)imidazol-2-

ylidene]silver(I)} hexafluorophosphate

silver(I) complex of (3-(carbomoylmethyl)-1-(2-cyanophenyl)-

imidazol-2-ylidene

[Rh(C–CN)(cod)]2(BF4)2

[Ru(p-cymene)(C–CN)Cl]2(BF4)2

[(C–CN)2Pd(μ-Cl)2Pd(CH3CN)2](BF4)2

xxxiv5b

6a

6b

7

8

9a

9b

10

11

12

13

14

15

16a

16b

17

18

19

20

21

22

23

{Pd(CH3CN)2}3(C–N–N–C)](BF4)4

[Pd(C–CN)(η1:η2-coe-OMe)(CH3CN)]BF4

[Pd(C–CN)(η1:η2-coe-OMe)]2(BF4)2

[Pt(C–CN)(cod)Cl]BF4

(Pt(C–CN)(η1:η2-coe-OMe)Cl

[Pt(C–CN)(η1:η2-coe-OMe)(CH3CN)]BF4

[Pt(C–CN)(η1:η2-coe-OMe)]2(BF4)2

[Ag(IMes)2]BF4

[Pt(IMes)(cod)Cl]BF4

[Ni(C–NH2)2](PF6)2

[Ru(p-cymene)(C–NH2)Cl]PF6

[Os(p-cymene)(C–NH2)Cl]PF6

[RuCp*(C–NH2)(py)]PF6

[RuCp*(P–NH2)(py)]PF6

RuCp*(κ2(P,N)-PPh2CH2CH2NH2)Cl

[Ru(p-cymene)(C–NH2)H]PF6

[Ru(p-cymene)(C–NMe2)Cl]PF6·1.5 DMSO

[IrCp*(C–NH2)Cl]PF6

[IrCp*(P–NH2)Cl]PF6

[IrCp*(C–NH2)H]PF6

[IrCp*(C–NMe2)Cl]PF6

[RuCp*(C–NH2)(CO)]PF6

xxxv24

app

APT

atm

BINAP

BINOL

Bu

Bu4N

C/B/S

C–CN

CD

C–NH2

C–NMe2

cod

coe-OMe

Cp

Cp*

CpH

DFT

DMSO

[RuCp*(P–NH2)(CO)]PF6

2-amido-2-(2-pyridyl)-propane

atomic polar tensor

atmosphere

2,2'-bis(diphenylphosphino)-1,1'-binaphthyl

1,1'-bi-2-naphthol

butyl

tetrabutylammonium

catalyst to base to substrate

nitrile functionalized N-heterocyclic carbene/

1-(2-cyanophenyl)-3-methylimidazol-2-ylidene

circular dichroism

primary amino-functionalized N-heterocyclic carbene/

1-(2-aminomethylphenyl)-3-methylimidazol-2-ylidene

1-(N,N-dimethylaminopropyl)-3-methylimidazol-2-ylidene

1,5-cyclooctadiene

2-methoxycyclooct-5-enyl

cyclopentadienyl

pentamethylcyclopentadienyl

cyclopentadiene

Density Functional Theory

dimethylsulfoxide

xxxvi(L)-DOPA

dpen

dpim

dpmp

dppe

dppm

en

eq

equiv

ESI-MS

ESU

Et

FID

GC

HC–NMe2

HMBC

HRMS

HSQC

ICy

IMes

IMesH

imid

(L)-3,4-dihydroxyphenylalanine

1,2-diphenylethylenediamine

1,3-diphenyl-2-imidazolidinylidenato-2-C,2'-C

bis((diphenylphosphino)methyl)phenylphosphine

1,2-bis(diphenylphosphino)ethane

1,1-bis(diphenylphosphino)methane

ethylenediamine

equation/equilibrium

equivalent

Electrospray Ionization Mass Spectrometry

electrostatic unit

ethyl

flame ionization detector

gas chromatography

1-(N,N-dimethylamino)propyl-3-methylimidazolium

Heteronuclear Mutiple-bond Correlation

High Resolution Mass Spectrometry

Heteronuclear Single-quantum Correlation

1,3-dicyclohexylimidazol-2-ylidene

1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene

1,3-bis(2,4,6-trimethylphenyl)imidazolium

imidazol-2-ylidene

xxxviiiPr

IPr

IR

KIE

MEA

MS

NAA

NHC

NMR

N–N

NOESY

ORTEP

papH

PCy3

PiPr3

P–NH2

P–N–N–P

P2(NH)2

PPh3

ppm

py

pyCH2

isopropyl

bis(2,6-diisopropylphenyl)imidazol-2-ylidene

infrared

kinetic isotope effect

2-methyl-5-ethyl-aniline

mass spectrometry

N-alkylated aniline

N-heterocyclic carbene

Nuclear Magnetic Resonance

2-hydroxylphenylbis(pyrazol-1-yl)methane and other derivatives

Nuclear Overhauser Effect Spectroscopy

Oak Ridge Thermal-Ellipsoid Plot

2-phenyl-6-(2 aminoisopropyl)pyridine

tricyclohexylphosphine

triisopropylphosphine

phosphine-amine/2-(diphenylphosphino)benzylamine

tetradentate diphosphinediimine ligand

tetradentate diphosphinediamine ligand

triphenylphosphine

parts per million

pyridine

2'-pyridylmethyl

xxxviiiQST

quinCH2

rac

ROMP

tBu

tert

THF

tmen

TMS

TOF

tot

TRISPHAT

Ts

UV-vis

Quadratic Synchronous Transit

2'-quinolylmethyl

racemic

ring opening metathesis polymerization

tert-butyl

tertiary

tetrahydrofuran

2,3-dimethylbutane-2,3-diamine

tetramethylsilane

turnover frequency

total

tris[tetrachlorobenzene-1,2-bis(olato)]phosphate

p-toluenesulfonyl

ultraviolet-visible

1Chapter 1: Introduction

The catalytic homogeneous hydrogenation of polar double bonds using molecular hydrogen is

an important industrial process to give valuable organic building blocks such as alcohols and

amines for use as fragrance and pharmaceutical precursors. Late transition metal catalysts using

certain phosphine ligands and phosphine-amine ligands have exceptional activity in the

hydrogenation of polar double bonds. The studies of these, including the proposed mechanisms

of action, have been extensively reviewed in the literature.1 The emergence of N-heterocyclic

carbenes (NHC) as ligands for use in homogeneous catalysis in the past two decades has exciting

implications as these ligands in general form strong metal-carbon bonds, and they are greener

and less toxic compared to their phosphine counterparts.2 This introduction reviews the

importance of metal-dihydrogen and metal hydride complexes in homogeneous catalysis, the

mechanisms of polar double bond reduction by molecular hydrogen, and the recent applications

of phosphines and donor-functionalized NHC in homogeneous catalysis.

1.1 Homogeneous Catalysis Involving Metal-Dihydrogen and Metal-Hydrides Complexes

1.1.1 The Metal-Dihydrogen Bond. A dihydrogen complex is often an intermediate in the

oxidative addition of dihydrogen to a transition metal center leading to the formation of a metal

dihydride complex. Such a complex is considered to be an important intermediate in the

hydrogenation of alkenes catalyzed by rhodium(I)- and ruthenium(II)-based Wilkinson's

catalysts.3 Kubas isolated the first octahedral side-on dihydrogen metal complex, W(η2-H2)

(CO)3(PCy3)2 (PCy3 = tricyclohexylphosphine) in 1984. He described such a interaction between

an η2-H2 ligand and the transition metal as a three-center two electron bond.4 Crabtree called this 1. (a) Rosales, M., Coord. Chem. Rev. 2000, 196, 249-280; (b) Noyori, R.; Yamakawa, M.; Hashiguchi, S.,

J. Org. Chem. 2001, 66, 7931-7944; (c) Clapham, S. E.; Hadzovic, A.; Morris, R. H., Coord. Chem. Rev. 2004, 248, 2201-2237; (d) Samec, J. S. M.; Bäckvall, J. E.; Andersson, P. G.; Brandt, P., Chem. Soc. Rev. 2006, 35, 237-248; (e) Ikariya, T.; Murata, K.; Noyori, R., Org. Biomol. Chem. 2006, 4, 393-406; (f) Ito, M.; Ikariya, T., Chem. Commun. 2007, 5134-5142; (g) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J., Chem. Rev. 2010, 110, 2294-2312; (h) Kuwata, S.; Ikariya, T., Dalton Trans. 2010, 39, 2984-2992; (i) Ikariya, T., Bull. Chem. Soc. Jpn. 2011, 84, 1-16.2. (a) Herrmann, W. A., Angew. Chem. Int. Ed. 2002, 41, 1290-1309; (b) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (c) Hahn, F. E.; Jahnke, M. C., Angew. Chem. Int. Ed. 2008, 47, 3122-3172; (d) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (e) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676; (f) Poyatos, M.; Mata, J. A.; Peris, E., Chem. Rev. 2009, 109, 3677-3707.3. Kubas, G. J., Acc. Chem. Res. 1988, 21, 120-128.4. Kubas, G. J.; Ryan, R. R.; Swanson, B. I.; Vergamini, P. J.; Wasserman, H. J., J. Am. Chem. Soc. 1984, 106, 451-452.

2class of η2-H2 metal complexes as σ-complexes to cover a variety of η2-σ-bonded ligands (C–H

and Si–H) in order to describe accurately the synergistic interaction between the σ-orbital of H2

and the dσ orbital on the metal, and between the σ*-orbital of H2 and the dπ orbital of the metal

(Figure 1.1).5

Figure 1.1. Bonding scheme of the η2-H2 ligand on a transition metal center.

Now hundreds of dihydrogen complexes have been isolated and structurally characterized by

diffraction methods (X-ray and neutron) and various NMR techniques. These non-classical

dihydride complexes contain a range of H–H bond lengths (0.8 – 1.4 Å) as a continuum

depending on the magnitude of the σ and σ* interactions.6 Metal dihydrides are at one end of the

continuum with H–H distances (dHH) of more than 1.6 Å, while dihydrogen complexes have dHH

between 0.8 – 1.2 Å on the other extreme.6 Although the H–H distances can rarely be directly

measured, especially the ones in between the two regimes, they can be accurately determined

using mathematical models based on T1 measurements and JHD coupling constants that are

obtained spectroscopically.6 Morris proposed the first equation to relate dHH with the JHD values

that were measured for several late transition metal dihydrogen complexes.7 This has been

extended recently to cover more precisely those of iron, ruthenium, and osmium.6f

1.1.2 The Acid-base Reactivity of Metal Hydrides and Metal Dihydrogen Complexes. The

acidities of those complexes have been measured and placed on pKa scales. Following the work

that was conducted by Heinekey, Norton and Angelici in the determination of the pKa values and

the bond dissociation energies of a collection of hydride complexes,8 the Morris group

constructed pKa ladders in tetrahydrofuran to cover the acidities of metal hydride and phosphine-

containing compounds over a 35 pKa unit range.9 In one case, a hydride ligand on trans- 5. (a) Crabtree, R. H.; Hamilton, D. G., Adv. Organomet. Chem. 1988, 28, 299-338; (b) Crabtree, R. H.,

Angew. Chem. Int. Ed. 1993, 32, 789-805.6. (a) Jessop, P. G.; Morris, R. H., Coord. Chem. Rev. 1992, 121, 155-284; (b) Heinekey, D. M.; Oldham, W. J., Chem. Rev. 1993, 93, 913-926; (c) Morris, R. H., Can. J. Chem. 1996, 74, 1907-1915; (d) Peruzzini, M.; Poli, R., Eds. Recent Advances in Hydride Chemistry; Elsevier: Amsterdam, 2001; (e) Kubas, G. J., Chem. Rev. 2007, 107, 4152-4205; (f) Morris, R. H., Coord. Chem. Rev. 2008, 252, 2381-2394.7. Maltby, P. A.; Schlaf, M.; Steinbeck, M.; Lough, A. J.; Morris, R. H.; Klooster, W. T.; Koetzle, T. F.; Srivastava, R. C., J. Am. Chem. Soc. 1996, 118, 5396-5407.

HH

M

dπ

σ *H

HM

dσ

σ

3Fe(H)2(diphosphine)2 was protonated by alcohols (HOR) giving the dihydrogen complex trans-

[Fe(η2-H2)(H)(diphosphine)2]OR10 (pKaTHF of trans-Fe(η2-H2)(H)(dppe)2]BPh4 = 13,9a dppe =

1,2-bis(diphenylphosphino)ethane). The polyhydride complex IrH5(PiPr3)2 (pKaTHF ≥ 43, PiPr3 =

triisopropylphosphine),9a when reacted with KH and a diaza-crown ether, forms the anionic

polyhydride complex [IrH4(PiPr3)2]-, in which one of the hydride ligands forms a hydridic-

protonic bond with the N–H group of the diaza-crown ether.11 In this case, the hydride ligand

acts as a hydrogen bond acceptor. The dihydrogen ligand, on the other hand, can act as a

hydrogen bond donor in the complex trans-Ru(dppe)2(η2-H2... OSO2CF3)CN, when the parent

complex Ru(dppe)2(OSO2CF3)CN is reacted with an atmosphere of hydrogen in methylene

chloride at -10°C.12 All these reactions are relevant to the intramolecular heterolytic splitting of

H2 at a transition metal center.

1.1.3 The Heterolytic Splitting of H2 at a Transition Metal Center and Implications for

Catalysis. One could view the heterolytic splitting of H2 when reacted with a base (B) in the

presence of a metal center (M) as a type of Brønsted acid chemistry giving an H+ and H-

equivalent.6d The extent of this reaction depends on the relative acidities of the coordinated

dihydrogen ligand and the Brønsted-base partner as discussed above (eq 1.1):

M(H2) + B M(H-) + B(H+) (1.1)

When the ligand (L) of a transition metal complex is suitably functionalized and is in close

proximity to the coordinated η2-H2 ligand, the intramolecular heterolytic splitting of the η2-H2

may occur to give a M–H/L–H couple. Chaudret, Lau and others have shown that a

ruthenium(II) diphosphine complex can undergo reversible proton exchange from the amine arm

of the functionalized cyclopentadienyl ring with the η2-H2 ligand, forming a quaternary amine

8. (a) Chinn, M. S.; Heinekey, D. M., J. Am. Chem. Soc. 1987, 109, 5865-5867; (b) Chinn, M. S.; Heinekey, D. M., J. Am. Chem. Soc. 1990, 112, 5166-5175; (c) Kristjansdottir, S. S.; Moody, A. E.; Weberg, R. T.; Norton, J. R., Organometallics 1988, 7, 1983-1987; (d) Weberg, R. T.; Norton, J. R., J. Am. Chem. Soc. 1990, 112, 1105-1108; (e) Kristjansdottir, S. S.; Loendorf, A. J.; Norton, J. R., Inorg. Chem. 1991, 30, 4470-4471; (f) Angelici, R. J., Acc. Chem. Res. 1995, 28, 51-60; (g) Wang, D. M.; Angelici, R. J., J. Am. Chem. Soc. 1996, 118, 935-942.9. (a) Jia, G.; Lough, A. J.; Morris, R. H., Organometallics 1992, 11, 161-171; (b) Abdur-Rashid, K.; Fong, T. P.; Greaves, B.; Gusev, D. G.; Hinman, J. G.; Landau, S. E.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2000, 122, 9155-9171; (c) Li, T.; Lough, A. J.; Zuccaccia, C.; Macchioni, A.; Morris, R. H., Can. J. Chem. 2006, 84, 164-175; (d) Li, T.; Lough, A. J.; Morris, R. H., Chem. Eur. J. 2007, 13, 3796-3803.10. Baker, M. V.; Field, L. D.; Young, D. J., Chem. Commun. 1988, 546-548.11. (a) Abdur-Rashid, K.; Gusev, D. G.; Landau, S. E.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 1998, 120, 11826-11827; (b) Landau, S. E.; Groh, K. E.; Lough, A. J.; Morris, R. H., Inorg. Chem. 2002, 41, 2995-3007.12. Fong, T. P.; Forde, C. E.; Lough, A. J.; Morris, R. H.; Rigo, P.; Rocchini, E.; Stephan, T., Dalton Trans. 1999, 4475-4486.

4salt on the ligand and a metal hydride (Figure 1.2).13 Our group has also observed such an

exchange process from an iridium hydride with a proton on a nitrogen of a sulfur-bonded

thiopyridine ligand.14 In fact, the “NH effect” in polar double bond hydrogenation is based on

this concept (see Section 1.2).

Figure 1.2. Reversible proton exchange of a η2-H2 ligand with a pendant amine arm in a

ruthenium(II) complex containing a diphosphine ligand.

The aforementioned reaction involving the intramolecular heterolytic splitting of H2 can be

extended to the intermolecular regime using external bases. This has important implications for

catalysis. Norton and coworkers have shown that iminium ions can be hydrogenated at 50 psi at

room temperature giving primary amine salts using CpRu(diphosphine)H as the catalyst. In the

catalytic cycle, they have proposed a stepwise mechanism involving first the hydride transfer to

the iminium ion forming a primary amine. The coordination of H2 to the acidic metal center then

follows. Protonation of the product amine by the η2-H2 ligand leads to a primary amine salt. This

is an example of an ionic hydrogenation as the dihydrogen ligand on the transition metal must be

acidic enough to protonate the substrate during the catalytic cycle and the resulting hydride is

hydridic enough to attack the iminium ion.15 A more recent example was reported by Crabtree

and workers in the hydrogenation of quinolines catalyzed by an iridium(I) complex giving

tetrahydroquinolines. A polyhydride iridium(III) complex, [Ir(η2-H2)(H)2(NHC)(PPh3)2]+, was

proposed to be an intermediate in the catalytic cycle. This again involves stepwise protonation of

the substrate by the η2-H2 ligand, and a hydride attack by the Ir–H to the double bond of the

substrate, all occurring in the outer coordination sphere (Figure 1.3).16 These examples show that

molecular hydrogen, when coordinated to a transition metal center, can be acidic enough to

13. (a) Chu, H. S.; Lau, C. P.; Wong, K. Y.; Wong, W. T., Organometallics 1998, 17, 2768-2777; (b) Ayllon, J. A.; Sayers, S. F.; Sabo-Etienne, S.; Donnadieu, B.; Chaudret, B.; Clot, E., Organometallics 1999, 18, 3981-3990.14. Lough, A. J.; Park, S.; Ramachandran, R.; Morris, R. H., J. Am. Chem. Soc. 1994, 116, 8356-8357.15. (a) Magee, M. P.; Norton, J. R., J. Am. Chem. Soc. 2001, 123, 1778-1779; (b) Guan, H. R.; Iimura, M.; Magee, M. P.; Norton, J. R.; Zhu, G., J. Am. Chem. Soc. 2005, 127, 7805-7814.16. Dobereiner, G. E.; Nova, A.; Schley, N. D.; Hazari, N.; Miller, S. J.; Eisenstein, O.; Crabtree, R. H., J. Am. Chem. Soc. 2011, 133, 7547-7562.

Ru

PPh2

Ph2P+ HH

NMe2n

Ru

PPh2

Ph2P

+

H

H

NMe2n

n = 2, 3

5undergo heterolytic splitting with an aid of an external base (B), for example, an amine, giving a

metal hydride and the protonated base (HB).

Figure 1.3. The catalytic hydrogenation of iminium cations (above) and quinolines (below)

catalyzed by ruthenium(II) and iridium(III) catalysts involving an [M](η2-H2) intermediate (M =

Ru or Ir).

1.1.4 Metal Hydrides in Homogeneous Hydrogenation Reactions. Metal hydrides play a

central role in homogeneous hydrogenation reactions. Many important reactions, including the

hydrogenation and isomerization of alkenes, involve the addition of a hydride to a coordinated

double bond (C=C).17 The hydricities of transition metal hydrides can be quantified to compare

the propensity of hydride loss from the metal center, and therefore, the reactivity of these

hydrides. In most cases, however, this has proven to be difficult. There have been some reports

of their thermodynamic properties.18

One of the important reactions is the hydrogenation of terminal alkenes catalyzed by

Wilkinson's catalyst.19 The catalytic hydrogenation reaction using the rhodium(I) catalyst,

RhCl(PPh3)3 (PPh3 = triphenylphosphine), proceeds by first the dissociation of PPh3. Hydrogen

oxidatively adds on rhodium(I) to form a rhodium(III) dihydride complex Rh(H)2Cl(PPh3)2. The

alkene coordinates to the metal center, and hydride migration to the alkene then occurs.

Reductive elimination of the hydride ligand and the metal alkyl affords the product alkane and

17. de Vries, J. G.; Elsevier, C. J., Eds. The Handbook of Homogeneous Hydrogenation; Wiley-VCH: Weinheim, Germany, 2004; Vol 1-3.18. (a) Nietlispach, D.; Bakhmutov, V. I.; Berke, H., J. Am. Chem. Soc. 1993, 115, 9191-9195; (b) Ciancanelli, R.; Noll, B. C.; DuBois, D. L.; DuBois, M. R., J. Am. Chem. Soc. 2002, 124, 2984-2992.19. (a) Evans, D.; Osborn, J. A.; Jardine, F. H.; Wilkinson, G., Nature 1965, 208, 1203-1204; (b) Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G., J. Chem. Soc. A 1966, 1711-1732.

Ru

PPh2

Ph2P H

N+BF4

NH+

BF4

cat.

H2 (50 psi), rt

IrN

N

HPh3P

PPh3

H

H H

cat.

H2 (1 atm), 35°CN N

HToluene

CH2Cl2

+

6regenerates the rhodium(I) form of the catalyst. The cycle then turns over (Scheme 1.1).20 The

ruthenium(II) analogue, RuHCl(PPh3)3, is known to catalyze the hydrogenation of alkenes and

the mechanism of action has been well studied by Halpern.19a, 21 Other catalysts such as

Crabtree's catalyst, [Ir(cod)(py)(PCy3)]+ (cod = 1,5-cyclooctadiene; py = pyridine)22 and the

cationic rhodium complex, [Rh(diphosphine)(CH3OH)2]+, are used for the hydrogenation of

substituted alkenes with functional group tolerance.23 The use of a chiral diphosphine with the

latter catalyst system allows the mass production of the enantiopure product, (L)-DOPA, in one

of Monsanto's processes.24 This is an important drug in the treatment of Parkinson's disease.

These catalysts are shown to have the oxidative addition of dihydrogen to the metal center as one

of the key step in the catalytic cycle.

Scheme 1.1. The Proposed Mechanism for the Hydrogenation of Terminal Alkenes Catalyzed by

the Rhodium(I)-based Wilkinson's Catalyst.

20. (a) Meakin, P.; Jesson, J. P.; Tolman, C. A., J. Am. Chem. Soc. 1972, 94, 3240-3242; (b) Halpern, J.; Okamoto, T.; Zakhariev, A., J. Mol. Cat. 1977, 2, 65-68.21. Fordyce, W. A.; Wilczynski, R.; Halpern, J., J. Organomet. Chem. 1985, 296, 115-125.22. (a) Crabtree, R. H.; Felkin, H.; Morris, G. E., J. Organomet. Chem. 1977, 141, 205-215; (b) Crabtree, R. H.; Felkin, H.; Fillebeenkhan, T.; Morris, G. E., J. Organomet. Chem. 1979, 168, 183-195; (c) Cui, X. H.; Burgess, K., Chem. Rev. 2005, 105, 3272-3296; (d) Church, T. L.; Andersson, P. G., Coord. Chem. Rev. 2008, 252, 513-531.23. (a) Halpern, J.; Riley, D. P.; Chan, A. S. C.; Pluth, J. J., J. Am. Chem. Soc. 1977, 99, 8055-8057; (b) Chan, A. S. C.; Pluth, J. J.; Halpern, J., J. Am. Chem.. Soc. 1980, 102, 5952-5954; (c) Landis, C. R.; Halpern, J., J. Am. Chem. Soc. 1987, 109, 1746-1754.24. Knowles, W. S., Angew. Chem. Int. Ed. 2002, 41, 1998-2007.

RhPh3P

PPh3ClH2

RhH

PPh3

HCl

PPh3

RhH

HClPPh3 R

Rh

PPh3

HPPh3

R

H

R

HH

- PPh3

RhPPh3Ph3P

PPh3Cl

RPPh3

Cl

71.2 Mechanisms of the Hydrogenation of Polar Double Bonds

1.2.1 Ketone Hydrogenation, the Outer-sphere Mechanism and the “NH Effect”. Early

attempts to hydrogenate aldehydes and ketones used ruthenium catalysts Ru(η2-H2)(H)2(PPh3)325

and cis-RuH2(PPh3)426 with hydrogen or alcohol as the reductant, respectively. Although these

reactions proceed smoothly at room temperature, the hydride affinity to the polar double bond is

low and the substrate scope is limited. For the design of highly active catalysts for polar double

bond reduction, the use of strong donor ligands is needed to stabilize the conjugate Lewis acid

from the metal hydride complex in order to favor the attack of the polar double bond. In addition,

the use of a strong trans-influence ligand across the metal from the hydride can labilize the metal

hydride bond and makes it more reactive.1c

Early work conducted by Noyori and co-workers used a diphosphine ligand on ruthenium for

ketone hydrogenation. The asymmetric hydrogenation of ketones using H2 was achieved with an

enantiomeric excess of up to 99% using an enantiopure BINAP ligand (BINAP = 2,2'-

bis(diphenylphosphino)-1,1'-binaphthyl) in the system [Ru(η6-arene)((S)-BINAP)(halide)]+.27

This process uses a relatively high pressure of H2 (up to 100 atm) at 30°C. Later the same

research group discovered that the addition of a diamine ligand in the reaction pot containing

RuCl2(diphosphine)(solvent)2 and potassium hydroxide catalyzed the H2-hydrogenation of

ketones under a low pressure of H2 (4 atm) at room temperature with a substrate to catalyst

loading of 500/1.28 When a chiral diphosphine was used, an enantiomeric excess up to 99% was

obtained.28-29 Noyori called the positive influence of the diamine on catalysis the “NH effect”,1b,

30 as it was shown that the absence of an NH group in these catalytic systems resulted in lower

activity. Much effort has been devoted to study the importance of the “NH effect” in bifunctional

catalysis, including the work of Baratta,31 Bergens,32 Clarke,33 Ikariya,34 Wills35 and many

others.36

25. (a) Cole-Hamilton, D. J.; Wilkinson, G., New J. Chem. 1977, 1, 141-155; (b) Linn, D. E.; Halpern, J., J. Am. Chem. Soc. 1987, 109, 2969-2974.26. (a) Imai, H.; Nishiguchi, T.; Fukuzumi, K., J. Org. Chem. 1976, 41, 665-671; (b) Hayashi, Y.; Komiya, S.; Yamamoto, T.; Yamamoto, A., Chem. Lett. 1984, 1363-1366.27. Mashima, K.; Kusano, K. H.; Ohta, T.; Noyori, R.; Takaya, H., Chem. Commun. 1989, 1208-1210.28. Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R., J. Am. Chem. Soc. 1995, 117, 2675-2676.29. Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R., Angew. Chem. Int. Ed. 1998, 37, 1703-1707.30. (a) Noyori, R.; Ohkuma, T., Angew. Chem. Int. Ed. 2001, 40, 40-73; (b) Noyori, R., Angew. Chem. Int. Ed. 2002, 41, 2008-2022.31. Baratta, W.; Ballico, M.; Esposito, G.; Rigo, P., Chem. Eur. J. 2008, 14, 5588-5595.32. Leong, C. G.; Akotsi, O. M.; Ferguson, M. J.; Bergens, S. H., Chem. Commun. 2003, 750-751.33. Phillips, S. D.; Fuentes, J. A.; Clarke, M. L., Chem. Eur. J. 2010, 16, 8002-8005.

8Noyori and co-workers proposed that the bifunctional catalysis of ketone hydrogenation

involves the dual action of the metal hydride and the protic amine group. It was proposed this

proceeds via a six-membered pericyclic transition state involving hydrogen bonding of the N-H

group with the oxygen of the ketone and attack of the carbonyl group by the metal hydride. The

concerted transfer of the H+/H- pair to the ketone affords the product alcohol, and a metal-amido

bond is formed. A hydrogen molecule then coordinates to the metal center in a side-on fashion.

The amido nitrogen, which acts as a strong Lewis base, is responsible for the heterolytic splitting

of the η2-H2 ligand, forming an N–H and an M–H bond (Scheme 1.2).1b-f, 1i Significantly, Noyori

and co-workers have isolated all the intermediates in this bifunctional mechanism using the

precatalyst RuCl(η6-p-cymene){(S,S)-TsNCHPhCHPhNH2} (TsNCHPhCHPhNH2 = N-(p-

toluenesulfonyl)-1,2-diphenylethylene-diamine) and KOH in the transfer hydrogenation of

ketones in 2-propanol, which serves as the hydrogen source. These include the hydride-amine

complex RuH(η6-p-cymene){(S,S)-TsNCHPhCHPhNH2} and the amido complex Ru(η6-p-

cymene){(S,S)-TsNCHPhCHPhNH}. They showed identical activities compared to the activated

precatalyst in the transfer hydrogenation of ketones in 2-propanol. No base was required for

catalysis (Figure 1.4).37

Scheme 1.2. The Outer Sphere Bifunctional Mechanism Using the “NH effect” for the

Hydrogenation of Aromatic Ketones.

34. Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T., Organometallics 2001, 20, 379-381.35. Soni, R.; Cheung, F. K.; Clarkson, G. C.; Martins, J. E. D.; Graham, M. A.; Wills, M., Org. Biomol. Chem. 2011, 9, 3290-3294.36. (a) Standfest-Hauser, C.; Slugovc, C.; Mereiter, K.; Schmid, R.; Kirchner, K.; Xiao, L.; Weissensteiner, W., Dalton Trans. 2001, 2989-2995; (b) Lundgren, R. J.; Rankin, M. A.; McDonald, R.; Schatte, G.; Stradiotto, M., Angew. Chem. Int. Ed. 2007, 46, 4732-4735; (c) Ma, G. B.; McDonald, R.; Ferguson, M.; Cavell, R. G.; Patrick, B. O.; James, B. R.; Hu, T. Q., Organometallics 2007, 26, 846-854.37. Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R., Angew. Chem. Int. Ed. 1997, 36, 285-288.

[M]

N

D

H

H2

OR'

OHH

R'

R

R

[M]

N

D

H

H

H

[M]

N

D

H

HH

[M]H

N

D

HH

O

R'

R

D = Donor ligand

9Our recent research program involved a study of the bifunctional action of the catalyst

systems RuHX(diamine)(phosphine)2 (X = H, BH4, H, OR) in the asymmetric H2-hydrogenation

of ketones and imines.38 The key intermediates of the catalytic cycle involving a trans-dihydride-

amine group and a monohydrido-amido group attached to the metal center have been identified

and structurally characterized.38a, 38b, 38g, 38h Among all of these catalysts, the complexes trans-

Ru(H)2((R)-BINAP)(tmen) and (OC-6-22)-Ru(H)2(PPh3)2(tmen) (tmen = 2,3-dimethylbutane-

2,3-diamine) were found to have the heterolytic splitting of a coordinated η2-H2 ligand on the

active species as the rate-determining step according to various experimental and theoretical

studies.38a, 38b, 38g, 38i These are active catalysts, without prior activation by base, and catalyze

efficiently the reduction of ketones by H2 under very mild conditions in non-polar solvents. The

corresponding coordinatively unsaturated complexes containing a ruthenium-amido bond were

isolated, and these were also found to activate dihydrogen to give the trans-dihydride complexes

(Figure 1.4).38a, 38b, 38g

Figure 1.4. Examples of ruthenium(II) complexes with hydride-amine or an amido group that

catalyze the hydrogenation of ketones under base free conditions.

1.2.2 Effect of Alcohols on the Outer-sphere Bifunctional Mechanism using the “NH

Effect”. Many research groups have found that the presence of alcohols in bifunctional catalysis

accelerates the catalytic hydrogenation of ketones. For example, Ikariya34 and Andersson39 have

found that their ruthenium(II) catalyst systems, RuCp*(diamine)Cl, catalyze efficiently the

hydrogenation of ketones using molecular hydrogen. Deuterium labelling studies conducted by

38. (a) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2001, 123, 7473-7474; (b) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2002, 124, 15104-15118; (c) Rautenstrauch, V.; Hoang-Cong, X.; Churlaud, R.; Abdur-Rashid, K.; Morris, R. H., Chem. Eur. J. 2003, 9, 4954-4967; (d) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529; (e) Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579; (f) Guo, R. W.; Chen, X. H.; Elpelt, C.; Song, D. T.; Morris, R. H., Org. Lett. 2005, 7, 1757-1759; (g) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2005, 127, 1870-1882; (h) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R. H., Organometallics 2007, 26, 5987-5999; (i) Zimmer-De Iuliis, M.; Morris, R. H., J. Am. Chem. Soc. 2009, 131, 11263-11269.39. Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G., J. Am. Chem. Soc. 2005, 127, 15083-15090.

RuH

HNN

H H

PPh2

Ph2PRu

N NH SO

ORu

H

NN

HPh3P

Ph3PH H

Ru

H

NN

HPh3P

Ph3PH H

H H

H H

10Ikariya and co-workers revealed that there was significant deuterium scrambling between the

hydrogen/deuterium gas and the hydroxyl group of the alcohol solvent. 34 Andersson have

computed a smaller energy barrier in the heterolytic splitting of the η2-H2 ligand with an alcohol

serving as a proton shuttle.39 The six-membered ring transition state of the heterolytic splitting

has the hydroxyl group of the alcohol in close proximity to the dihydrogen ligand and the N–H

group, forming two hydrogen-bonds (Figure 1.5). It was concluded that the presence of alcohol

can act as proton shuttle to assist the heterolytic splitting of the η2-H2 ligand.1f, 39-40 We have also

observed a similar effect of alcohol recently where the transition state has been computed.38h

Figure 1.5. The transition state of the alcohol-assisted heterolytic splitting of H2 calculated by

Andersson and co-workers using computational methods.

1.2.3 Concerted or Stepwise Transfer of a Proton/Hydride Couple from the Metal Center

to the Polar Double bond. There has been a debate whether the transfer of the M–H/N–H group

to the polar double bond is a concerted or a stepwise process. Bergens and co-workers have

observed a ruthenium(II) alkoxide complex trans-Ru((R)-BINAP)(H)(PhMeCHO)((R,R)-dpen))

(dpen = 1,2-diphenylethylenediamine) upon the reaction of the trans-dihydride complex, trans-

Ru((R)-BINAP)(H)2((R,R)-dpen)), and acetophenone at -78°C.41 They have also studied a similar

intermediate by using intermolecular trapping agents42 and in the hydrogenation of lactones.43

Gusev and co-workers have recently computed the catalytic cycle for the dehydrogenation of

alcohols catalyzed by the trans-dihydride osmium(IV) complex trans-Os(H)2(CO)(κ3(P,N,P)-

HN(C2H4PiPr2)2), and found there is a significant interaction of the N–H group with the 2-

propoxide anion in the transition state structure.44 An alkoxide complex of ruthenium(II), trans-

Ru(H)(OiPr)(CO)(κ3(P,N,P)-HN(C2H4PiPr2)2) was structurally characterized, and this was in fast

40. (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R., J. Am. Chem. Soc. 2003, 125, 13490-13503; (b) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q., J. Am. Chem. Soc. 2005, 127, 3100-3109; (c) Casey, C. P.; Johnson, J. B.; Jiao, X. D.; Beetner, S. E.; Singer, S. W., Chem. Commun. 2010, 46, 7915-7917.41. Hamilton, R. J.; Bergens, S. H., J. Am. Chem. Soc. 2008, 130, 11979-11987.42. Takebayashi, S.; Dabral, N.; Miskolzie, M.; Bergens, S. H., J. Am. Chem. Soc. 2011, 133, 9666-9669.43. Takebayashi, S.; Bergens, S. H., Organometallics 2009, 28, 2349-2351.44. Bertoli, M.; Choualeb, A.; Gusev, D. G.; Lough, A. J.; Major, Q.; Moore, B., Dalton Trans. 2011, 40, 8941-8949.

Ru

NN

H

HH

OH H

11equilibrium with the trans-dihydride complex, trans-Ru(H)2(CO)(κ3(P,N,P)-HN(C2H4PiPr2)2) in

solution.45

Casey and co-workers provided evidence to support a concerted transfer process for the

hydrogenation of aldehydes using the Shvo's type catalyst 2,5-Ph2-3,4-Tol2(η5-C4COH)

Ru(CO)2H (Figure 1.6).46 The products of the kinetic isotope effects measured upon deuteration

only at the metal hydride (kRuH/kRuD = 1.5 ± 0.2), and only at the hydroxyl group of the

pentadienyl ligand (kOH/kOD = 2.2 ± 0.1) is in good agreement with that measured for deuteration

at both sites (kRuH/OH/kRuD/OD = 3.6 ± 0.3). They further demonstrated that both the hydroxyl

group and the metal hydride were required for catalysis as no alkoxide complex was observed

when benzaldehyde was reacted with the complex, 2,5-Ph2-3,4-Tol2(η5-C4COSiEt3)Ru(CO)2H,

which lacked a hydroxyl group.46 Recent studies has been devoted to the analogous iron(II)

system, and a concerted transfer step was supported by experimental studies.47

Figure 1.6. Concerted transfer of a proton/hydride couple from the Shvo's type catalyst to

benzaldehyde.

1.2.4 The Inner Sphere Mechanism. The coordination of a ketone to a metal center during its

catalytic hydrogenation is a key step in the inner sphere mechanism (Scheme 1.3). In the case of

H2-hydrogenation, an alkoxide base is required to activate the precatalyst. This forms a strong

metal-alkoxide bond. A dihydrogen molecule then coordinates to one of the vacant coordination

sites in a side-on fashion. The alkoxide then acts as an internal base to heterolytically split the η2-

H2 ligand, giving a metal hydride and alcohol. The ketone then coordinates to the metal center

and is attacked by the metal-hydride in a four-membered ring transition state, leading back to the

metal alkoxide complex. The protonation of this alkoxide by H2 releases the product alcohol.1c

45. Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.; Gusev, D. G., Organometallics 2011, 30, 3479-3482. 46. Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.; Kavana, M., J. Am. Chem. Soc. 2001, 123, 1090-1100.47. Casey, C. P.; Guan, H., J. Am. Chem. Soc. 2009, 131, 2499-2507.

RuH

OC

O

OC

H

PhTolTol

PhO

H

RuH

OC

O

OC

H

PhTolTol

PhRu

OC

O

OC

PhTolTol

Ph

O

H OH

H H+

12Scheme 1.3. The Inner Sphere Mechanism for the H2-Hydrogenation of Aromatic Ketones.

The hydrogenation of β-keto-esters was a well known process using enantiomerically pure

catalysts of the types RuCl2(BINAP)(solvent)2 or [Ru(BINAP)(bisolefin)(solvent)2]2+ prior to the

discovery of the “NH effect”.48 It was proposed that the active catalyst was generated by

dehydrochlorination using hydrogen. The β-keto-ester then chelates to the metal center during

the catalytic cycle. Protonation of the ketone oxygen by HCl in the alcoholic solvent makes the

carbonyl carbon more electrophilic to facilitate the attack of the metal-hydride on the carbonyl

carbon. This releases the product alcohol. The acidic hydrogen on the η2-H2 ligand was

deprotonated by the alcoholic solvent to regenerate the active species for catalysis.17 Noyori and

co-workers have described the intramolecular attack of the metal hydride on the ketone σ-bonded

through the oxygen atom as a [2 + 2] addition. The required change in the geometry of the metal

complex to align the orbitals makes this process energetically demanding (Figure 1.7). The

presence of the chelating group, in the case of the hydrogenation of a β-keto-ester, favours a π-

interaction of the metal-hydride and the carbonyl group of the ketone.1b, 30a

Figure 1.7. Orbital interaction diagram showing the hydride attack on a σ-bonded ketone.

48. Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S., J. Am. Chem. Soc. 1987, 109, 5856-5858.

[M]H2

OR'

OHH

R'

R

R

OHR'

R

[M]

OHR'

R

H

H

[M]

O

R' R

H

[M]

OR'

R

H

MH

OH

CR

R'π *

MH

OH

CR

R'π *

131.3 Applications of Phosphines and N-Heterocyclic Carbenes in Catalysis

1.3.1 Applications of Phosphines in Catalysis. A phosphine ligand (PR3) is known to be a

strong σ-donor and a moderate π-acceptor using its σ* orbital to interact with the dπ orbital at the

metal center.49 The tuneable electronic and steric properties of the R substituent at phosphorus

makes a phosphine a very attractive and useful ligand in catalysis.50 Phosphines are used in many

of the important catalytic reactions including cross-coupling reactions, hydroformylation

reactions, metathesis reactions and more. Many of these have been studied and reviewed

extensively in the literature.51

Functionalized phosphine ligands containing either a phosphine donor (diphosphine) or a

nitrogen-based donor (P,N-type ligand) are important in the design of highly active catalysts

systems.52 The use of a chiral diphosphine ligand, JOSIPHOS (Figure 1.8), for example, in an

iridium catalyst provides high activity and high enantiomeric excess in the asymmetric

hydrogenation of imines.53 This was applied in the large scale production of an enantiomerically

pure N-alkylated aniline (NAA) from a MEA imine (MEA = 2-methyl-5-ethyl-aniline, Figure

1.8), an important intermediate for the synthesis of metolachlor.53b, 53d, 53e The chiral BINAP

ligand also has rich applications in the hydrogenation of alkenes and ketones (see Section 1.2).

Figure 1.8. The production of an (S)-N-alkylated aniline (NAA) using an iridium complex

containing a JOSIPHOS ligand as a catalyst.

49. Orpen, A. G.; Connelly, N. G., Chem. Commun. 1985, 1310-1311.50. (a) Tolman, C. A., Chem. Rev. 1977, 77, 313-348; (b) Mason, R.; Meek, D. W., Angew. Chem. Int. Ed. 1978, 17, 183-194; (c) Dias, P. B.; Depiedade, M. E. M.; Simoes, J. A. M., Coord. Chem. Rev. 1994, 135, 737-807.51. (a) Puddephatt, R. J., Chem. Soc. Rev. 1983, 12, 99-127; (b) Farina, V.; Krishnan, B., J. Am. Chem. Soc. 1991, 113, 9585-9595; (c) Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W., J. Am. Chem. Soc. 1993, 115, 9858-9859; (d) Kranenburg, M.; Vanderburgt, Y. E. M.; Kamer, P. C. J.; Vanleeuwen, P.; Goubitz, K.; Fraanje, J., Organometallics 1995, 14, 3081-3089; (e) Hartwig, J. F., Acc. Chem. Res. 1998, 31, 852-860; (f) Tang, W. J.; Zhang, X. M., Chem. Rev. 2003, 103, 3029-3069; (g) Grubbs, R. H., Tetrahedron 2004, 60, 7117-7140; (h) Trnka, T. M.; Grubbs, R. H., Acc. Chem. Res. 2001, 34, 18-29; (i) Surry, D. S.; Buchwald, S. L., Chem. Sci. 2011, 2, 27-50.52. Guiry, P. J.; Saunders, C. P., Adv. Synth. Catal. 2004, 346, 497-537.

N

OCH3

NH

OCH3cat.

H2

FePR2

PR'2

0.5 equiv [Ir(cod)Cl]2

14P,N-type ligands (P–N) are used in the asymmetric hydrogenation of hindered alkenes.22c, 54

These have a phosphine donor and a functionalized chiral oxazoline donor. Pfaltz and Burgess

showed that iridium(I) catalysts of the type [Ir(P–N)(cod)]+ have excellent activity in catalyzing

the asymmetric hydrogenation of tetrasubstituted alkenes to chiral alkanes in good enantiomeric

excess.22c, 54d On the other hand, certain phosphine ligands with a primary amine donor

(phosphine-amine ligand) form an important class of ligands that are used in the asymmetric

hydrogenation of polar double bonds. With well established synthetic procedures of such ligands

reported in the literature,55 the ruthenium(II) complexes containing such ligands have found

wide applications in the hydrogenation of ketones,33, 56 imines,38e imides,57 esters58 and in the

dehydrogenation of amine boranes.59 Many of these catalytic systems were found to utilize the

bifunctional mechanism using the “NH effect”.33, 57, 59

1.3.2 N-heterocyclic carbenes and their Late Transition Metal Complexes. Singlet carbenes

are excellent Lewis bases by virtue of their highest energy occupied molecular orbital on carbon.

Although free carbenes are highly reactive in nature, many organometallic complexes with

coordinated carbene ligands are known in the literature.60 When heteroatoms are attached to the

carbene carbon of an acyclic, bent singlet carbene, σ-withdrawing substituents tends to lower the

energy level of the non-bonding σ orbital (inductive effect); while π-donating substituents, for

example nitrogen atoms, raise the energy level of the empty π-orbital (mesomeric effect, Figure

1.9). This results in a large σ–π energy gap, providing an extra stabilization of the singlet ground

state on the sp2-hybridized carbene carbon.2c, 60e, 61 N-heterocyclic carbenes are the most

important cyclic, bent singlet carbene in which stabilization of the singlet state is achieved by

presence of two nitrogen π-donors adjacent to the carbene carbon. 53. (a) Spindler, F.; Pugin, B.; Blaser, H. U., Angew. Chem. Int. Ed. 1990, 29, 558-559; (b) Blaser, H. U.;

Buser, H. P.; Coers, K.; Hanreich, R.; Jalett, H. P.; Jelsch, E.; Pugin, B.; Schneider, H. D.; Spindler, F.; Wegmann, A., Chimia 1999, 53, 275-280; (c) Dai, L. X.; Tu, T.; You, S. L.; Deng, W. P.; Hou, X. L., Acc. Chem. Res. 2003, 36, 659-667; (d) Blaser, H. U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M., Adv. Synth. Catal. 2003, 345, 103-151; (e) Blaser, H. U.; Pugin, B.; Spindler, F.; Thommen, M., Acc. Chem. Res. 2007, 40, 1240-1250.54. (a) Helmchen, G.; Pfaltz, A., Acc. Chem. Res. 2000, 33, 336-345; (b) Braunstein, P.; Naud, F., Angew. Chem. Int. Ed. 2001, 40, 680-699; (c) McManus, H. A.; Guiry, P. J., Chem. Rev. 2004, 104, 4151-4202; (d) Roseblade, S. J.; Pfaltz, A., Acc. Chem. Res. 2007, 40, 1402-1411.55. Ito, M.; Osaku, A.; Kobayashi, C.; Shiibashi, A.; Ikariya, T., Organometallics 2009, 28, 390-393.56. (a) Guo, R.; Morris, R. H.; Song, D., J. Am. Chem. Soc. 2005, 127, 516-517; (b) Jia, W. L.; Chen, X. H.; Guo, R. W.; Sui-Seng, C.; Amoroso, D.; Lough, A. J.; Abdur-Rashid, K., Dalton Trans. 2009, 8301-8307.57. (a) Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T., J. Am. Chem. Soc. 2007, 129, 290-291; (b) Ito, M.; Kobayashi, C.; Himizu, A.; Ikariya, T., J. Am. Chem. Soc. 2010, 132, 11414-11415.58. (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P., Angew. Chem. Int. Ed. 2007, 46, 7473-7476; (b) Clarke, M. L.; Diaz-Valenzuela, M. B.; Slawin, A. M. Z., Organometallics 2007, 26, 16-19; (c) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saito, T., Adv. Synth. Catal. 2010, 352, 92-96.59. Blaquiere, N.; Diallo-Garcia, S.; Gorelsky, S. I.; Black, D. A.; Fagnou, K., J. Am. Chem. Soc. 2008, 130, 14034-14035.

15

Figure 1.9. Schematics showing the mesomeric effect to the electronic configuration and the

interactions of π-orbitals in the acyclic, bent singlet carbene N–C–N.

Since the initial discovery of Bertrand's carbene62 and Arduengo's stable cyclic

diaminocarbene, or N-heterocyclic carbene (NHC)63 (Figure 1.10), much work has been devoted

to study the properties of carbene donors. 2c, 60e, 61, 64 A study of the thermodynamic properties of

the NHC suggests its σ-donor property is superior to that of phosphines, as a result of the

presence of a high energy filled σ-orbital.65 Similar to phosphines, the tuneable electronics and

steric properties of an N-heterocyclic carbene makes it very attractive to be used as a ligand in

catalysis. Pioneering work conducted by Herrmann and co-workers on the use of the NHC-

containing complex, Pd(NHC)2I2, in Heck-coupling reactions revealed that such complexes are

more reactive, and are moisture, heat and oxygen tolerant compared to their phosphine

60. (a) Fischer, E. O.; Maasbol, A., Angew. Chem. Int. Ed. 1964, 3, 580-581; (b) Cardin, D. J.; Cetinkay.B; Lappert, M. F., Chem. Rev. 1972, 72, 545-574; (c) Schrock, R. R., J. Am. Chem. Soc. 1974, 96, 6796-6797; (d) Schrock, R. R., Acc. Chem. Res. 1979, 12, 98-104; (e) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G., Chem. Rev. 2000, 100, 39-91.61. de Frémont, P.; Marion, N.; Nolan, S. P., Coord. Chem. Rev. 2009, 253, 862-892.62. Igau, A.; Grutzmacher, H.; Baceiredo, A.; Bertrand, G., J. Am. Chem. Soc. 1988, 110, 6463-6466.63. Arduengo, A. J.; Harlow, R. L.; Kline, M., J. Am. Chem. Soc. 1991, 113, 361-363.64. (a) Leuthausser, S.; Schwarz, D.; Plenio, H., Chem. Eur. J. 2007, 13, 7195-7203; (b) Fantasia, S.; Petersen, J. L.; Jacobsen, H.; Cavallo, L.; Nolan, S. P., Organometallics 2007, 26, 5880-5889; (c) Fey, N.; Haddow, M. F.; Harvey, J. N.; McMullin, C. L.; Orpen, A. G., Dalton Trans. 2009, 8183-8196; (d) Gusev, D. G., Organometallics 2009, 28, 763-770; (e) Gusev, D. G., Organometallics 2009, 28, 6458-6461; (f) Droge, T.; Glorius, F., Angew. Chem. Int. Ed. Engl. 2010, 49, 6940-6952.65. Huang, J.; Jafarpour, L.; Hillier, A. C.; Stevens, E. D.; Nolan, S. P., Organometallics 2001, 20, 2878-2882.66. Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus, G. R. J., Angew. Chem. Int. Ed. 1995, 34, 2371-2374.

pπ

pπ

π

π ∗

n.b.

n.b. = non bonding

NC

N

NC

N

NC

N

π

π ∗

n.b.

pπ

pπ

π

π ∗

n.b.

O OC

N NC

16counterparts.66 Many of the palladium(II) based systems with NHC ligands are now used in C–C

coupling reactions.2a, 2b, 2d, 2e, 67 Grubbs and co-workers have successfully replaced one of the

tricyclohexylphosphines of their first generation catalyst, Ru(PCy3)2Cl2(CHPh) with an N-

heterocyclic carbene to give highly active catalysts, Ru(NHC)(PCy3)Cl2(CHPh), for diverse

applications in alkene metathesis reactions.68 The application of ruthenium complexes containing

N-heterocyclic carbene ligands in alkene metathesis reactions has recently been reviewed.69

Figure 1.10. The structures of Bertrand's and Arduengo's carbenes.

Many ruthenium(II) complexes containing N-heterocyclic carbenes were found to be useful in

the activation of heteroatom bonds of small molecules. Our group observed and isolated the first

ruthenium(II) hydride complex containing 1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidene

(IMes) as a ligand, with C–H bond activation on the mesityl group of the NHC ligand.70

Whittlesey and co-workers have studied this further and extended this to the activation of C–F

bonds.71 Of note, the highly active four-coordinate ruthenium(II) complex RuH(CO)(IMes)2+

induces C–H bond activation on the IMes ligand as indicated by labelling studies using D2 gas.72

On the other hand, the five coordinate ruthenium(II) complex RuH(NHC)4+ allows coordination

of H2, CO, N2, and O2. The hydrogen and oxygen molecules were found to coordinate in a side-

on fashion to the coordinatively unsaturated metal center.73 A coordinatively unsaturated

67. Kantchev, E. A. B.; O'Brien, C. J.; Organ, M. G., Angew. Chem. Int. Ed. 2007, 46, 2768-2813.68. Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.; Scholl, M.; Choi, T. L.; Ding, S.; Day, M. W.; Grubbs, R. H., J. Am. Chem.. Soc. 2003, 125, 2546-2558.69. Vougioukalakis, G. C.; Grubbs, R. H., Chem. Rev. 2010, 110, 1746-1787.70. Abdur-Rashid, K.; Fedorkiw, T.; Lough, A. J.; Morris, R. H., Organometallics 2004, 23, 86-94.71. (a) Chilvers, M. J.; Jazzar, R. F. R.; Mahon, M. F.; Whittlesey, M. K., Adv. Synth. Catal. 2003, 345, 1111-1114; (b) Burling, S.; Paine, B. M.; Nama, D.; Brown, V. S.; Mahon, M. F.; Prior, T. J.; Pregosin, P. S.; Whittlesey, M. K.; Williams, J. M. J., J. Am. Chem. Soc. 2007, 129, 1987-1995; (c) Diggle, R. A.; Kennedy, A. A.; Macgregor, S. A.; Whittlesey, M. K., Organometallics 2008, 27, 938-944; (d) Reade, S. P.; Acton, A. L.; Mahon, M. F.; Martin, T. A.; Whittlesey, M. K., Eur. J. Inorg. Chem. 2009, 1774-1785; (e) Reade, S. P.; Mahon, M. F.; Whittlesey, M. K., J. Am. Chem. Soc. 2009, 131, 1847-1861; (f) Panetier, J. A.; Macgregor, S. A.; Whittlesey, M. K., Angew. Chem. Int. Ed. 2011, 50, 2783-2786.72. Lee, J. P.; Ke, Z. F.; Ramirez, M. A.; Gunnoe, T. B.; Cundari, T. R.; Boyle, P. D.; Petersen, J. L., Organometallics 2009, 28, 1758-1775.73. (a) Burling, S.; Haller, L. J. L.; Mas-Marza, E.; Moreno, A.; Macgregor, S. A.; Mahon, M. F.; Pregosin, P. S.; Whittlesey, M. K., Chem. Eur. J. 2009, 15, 10912-10923; (b) Haller, L. J. L.; Mas-Marza, E.; Moreno, A.; Lowe, J. P.; Macgregor, S. A.; Mahon, M. F.; Pregosin, P. S.; Whittlesey, M. K., J. Am. Chem. Soc. 2009, 131, 9618-9619.

NP SiMe3N N N

17rhodium(I) complex containing NHC ligands (RhCl(NHC)2) reacts with oxygen forming an η2-

O2 complex and retains the same oxidation state on rhodium.74

Other late transition metal NHC complexes such as those of iridium and platinum have also

found applications in catalysis. Iridium(III) complexes containing [IrCp*(NHC)]2+ are useful

catalysts in the Oppenauer-type oxidation reaction, providing useful carbonyl compounds from

the corresponding alcohols.75 Peris and co-workers have found that these complexes are useful in

the transfer hydrogenation of carbon dioxide to a formate anion.76 Platinum(0) complexes

containing an NHC are useful for the hydrosilylation of terminal alkynes.77 Nolan and co-

workers have recently reported the use of stable gold(I) NHC complexes in the hydration of

alkenes, alkynes and nitriles under silver free conditions, and in the carboxylation of aromatic

and heteroaromatic C–H bonds (Figure 1.11).78

Figure 1.11. Examples of late transition metal complexes and their use in (a) the oxidation of

alcohols, (b) the hydrosilylation of a terminal alkyne, and in (c) the carboxylation of aromatic

and heteroaromatic C–H bonds (from top to bottom).

Some ruthenium(II) complexes containing NHC ligand were found to be useful catalysts for

the hydrogenation of alkenes.72, 79 Iridium(I) complexes containing a functionalized chiral

oxazoline group on the NHC ligand was found to be useful in the asymmetric hydrogenation of 74. Praetorius, J. M.; Allen, D. P.; Wang, R. Y.; Webb, J. D.; Grein, F.; Kennepohl, P.; Crudden, C. M., J.

Am. Chem. Soc. 2008, 130, 3724-3725.

cat.

Ir

NN

NNH3C

H3C

2+

O

K2CO3 , acetone40°C

HO H

N N

Pt

SiOSi

o-xylene80°C

cat.C6H13 + Me3Si O

SiO

SiMe3H3C H C6H13

SiMe

OSiMe3

OSiMe3

N N

Au

OHcat.

KOH, THF20°C

R

NHR'CO2 + HCl

R

NR'O

OH

18hindered alkenes (see Section 1.3.3).22c, 80 In addition, many ruthenium(II) and iridium(III)

complexes containing NHC ligands are highly active catalysts for the transfer hydrogenation of

ketones in basic 2-propanol solution.81 Recently,Whittlesey and co-workers have investigated

their ruthenium(II) complexes in the formation of C–C and C–N bonds from alcohols and amines

by the hydrogen borrowing methodology.82

1.3.3 Donor-functionalized N-heterocyclic carbenes and applications in catalysis. The

installation of a donor group adjacent to the nitrogen atom of the imidazolylidene ring provides a

donor-functionalized NHC ligand. There are many reports that the presence of such a donor

group provides extra stability to the catalyst, and sometimes unique activity to catalysis.2c, 2d, 2f, 83

The synthesis of the donor-functionalized NHC ligand requires the synthesis of an

unsymmetrical imidazolium salt.84 The most common way to access this class of imidazolium

salt is by direct alkylation of a substituted imidazole,85 or via a copper-catalyzed Ullman-

coupling reaction of imidazole and a functionalized aryl group, and then alkylation of the

resulting aryl-imidazole.86 Douthwaite and co-workers prepared chiral bis-imidazoles by the

reaction of a chiral diimine and tosylmethyl isocyanide in a 1,3-cycloaddition reaction.87 A

change in reaction conditions leads to the reaction of one imine group leading to the formation of

a chiral imidazole with an imine functional group.88

75. (a) Hanasaka, F.; Fujita, K.; Yamaguchi, R., Organometallics 2005, 24, 3422-3433; (b) Hanasaka, F.; Fujita, K.-i.; Yamaguchi, R., Organometallics 2006, 25, 4643-4647.76. Sanz, S.; Benitez, M.; Peris, E., Organometallics 2010, 29, 275-277.77. (a) Marko, I. E.; Sterin, S.; Buisine, O.; Mignani, G.; Branlard, P.; Tinant, B.; Declercq, J. P., Science 2002, 298, 204-206; (b) Buisine, O.; Berthon-Gelloz, G.; Briere, J. F.; Sterin, S.; Mignani, G.; Branlard, P.; Tinant, B.; Declercq, J. P.; Marko, I. E., Chem. Commun. 2005, 3856-3858; (c) De Bo, G.; Berthon-Gelloz, G.; Tinant, B.; Marko, I. E., Organometallics 2006, 25, 1881-1890.78. Nolan, S. P., Acc. Chem. Res. 2011, 44, 91-100.79. (a) Lee, H. M.; Smith, D. C.; He, Z. J.; Stevens, E. D.; Yi, C. S.; Nolan, S. P., Organometallics 2001, 20, 794-797; (b) Dharmasena, U. L.; Foucault, H. M.; dos Santos, E. N.; Fogg, D. E.; Nolan, S. P., Organometallics 2005, 24, 1056-1058; (c) Gandolfi, C.; Heckenroth, M.; Neels, A.; Laurenczy, G.; Albrecht, M., Organometallics 2009, 28, 5112-5121; (d) Horn, S.; Albrecht, M., Chem. Commun. 2011, 47, 8802-8804; (e) Horn, S.; Gandolfi, C.; Albrecht, M., Eur. J. Inorg. Chem. 2011, 2863-2868.80. (a) Hou, D. R.; Reibenspies, J.; Colacot, T. J.; Burgess, K., Chem. Eur. J. 2001, 7, 5391-5400; (b) Powell, M. T.; Hou, D.-R.; Perry, M. C.; Cui, X.; Burgess, K., J. Am. Chem. Soc. 2001, 123, 8878-8879.81. (a) Albrecht, M.; Miecznikowski, J. R.; Samuel, A.; Faller, J. W.; Crabtree, R. H., Organometallics 2002, 21, 3596-3604; (b) Burling, S.; Whittlesey, M. K.; Williams, J. M. J., Adv. Synth. Catal. 2005, 347, 591-594; (c) Corberan, R.; Peris, E., Organometallics 2008, 27, 1954-1958; (d) Zinner, S. C.; Rentzsch, C. F.; Herdtweck, E.; Herrmann, W. A.; Kuhn, F. E., Dalton Trans. 2009, 7055-7062; (e) Dyson, G.; Frison, J. C.; Whitwood, A. C.; Douthwaite, R. E., Dalton Trans. 2009, 7141-7151; (f) Gnanamgari, D.; Sauer, E. L. O.; Schley, N. D.; Butler, C.; Incarvito, C. D.; Crabtree, R. H., Organometallics 2009, 28, 321-325; (g) Cheng, Y.; Sun, J.-F.; Yang, H.-L.; Xu, H.-J.; Li, Y.-Z.; Chen, X.-T.; Xue, Z.-L., Organometallics 2009, 28, 819-823.82. Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J., Dalton Trans. 2009, 753-762.83. Kuhl, O., Chem. Soc. Rev. 2007, 36, 592-607.84. Benhamou, L.; Chardon, E.; Lavigne, G.; Bellemin-Laponnaz, S.; César, V., Chem. Rev. 2011, 111, 2705-2733.85. Chan, B.; Chang, N.; Grimmett, M., Aust. J. Chem. 1977, 30, 2005-2013.

19The general strategies in the complexation of these donor-functionalized NHC ligand starting

from their corresponding imidazolium salts requires (a) the generation of free carbene in situ, or

(b) the use of a transmetalation reagent. The former was achieved by Arnold and co-workers89,

for example, but free carbenes are known to react with functional groups that have an acidic

proton.90 The more desirable method is to generate a stable carbene complex such as those of

silver(I) in situ, and transmetalate the NHC ligand to another metal in a separate reaction or in

the same pot.91 Many late transition metal complexes have been successfully synthesized by this

method, although there are reports that the choice of the silver base (silver(I) oxide or silver(I)

carbonate) is crucial.92 Some of these silver(I) complexes containing donor-functionalized NHC

ligands such as those of pyridyl or amido are isolated and structurally characterized.92-93

The Grubbs-Hoveyda metathesis catalyst containing a tethered oxygen donor from the NHC

ligand to the ruthenium(II) center is an active catalyst for the asymmetric cross-metathesis and

ring-opening metathesis reactions of prochiral alkenes.94 This catalyst has a bidentate NHC

ligand functionalized with a chiral BINOL (1,1'-bi-2-naphthol) group attached to the nitrogen

atom of the NHC ring. Burgess and co-workers have found that the iridium(I) catalysts of the

type [Ir(C–N)(cod)]+, where the C–N ligand represents an NHC donor containing a chiral

oxazoline group, gave superior activity in the asymmetric hydrogenation of tetrasubstituted

alkenes with good enantiomeric excess compared to phosphine-based catalysts. Double bond

migration of the substrate molecule was not observed.22c, 80 Elsevier and co-worker have recently

developed a highly active catalyst for the transfer hydrogenation of alkynes to Z-alkenes using a

palladium(0) catalysts containing an NHC ligand with a tertiary amine donor. It was found that

amine group acts as an internal base during catalysis and no external base is required.95

86. Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M., Chem. Eur. J. 2004, 10, 5607-5622.87. Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R., Organometallics 2003, 22, 4384-4386.88. Bonnet, L. G.; Douthwaite, R. E.; Kariuki, B. M., Organometallics 2003, 22, 4187-4189.89. Arnold, P. L.; Mungur, S. A.; Blake, A. J.; Wilson, C., Angew. Chem. Int. Ed. 2003, 42, 5981-5984.90. (a) Enders, D.; Breuer, K.; Raabe, G.; Runsink, J.; Teles, J. H.; Melder, J. P.; Ebel, K.; Brode, S., Angew. Chem. Int. Ed. 1995, 34, 1021-1023; (b) Frey, G. D.; Lavallo, V.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G., Science 2007, 316, 439-441.91. (a) Garrison, J. C.; Youngs, W. J., Chem. Rev. 2005, 105, 3978-4008; (b) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B., Chem. Rev. 2009, 109, 3561-3598.92. Tulloch, A. A. D.; Danopoulos, A. A.; Winston, S.; Kleinhenz, S.; Eastham, G., Dalton Trans. 2000, 4499-4506.93. (a) Catalano, V. J.; Malwitz, M. A., Inorg. Chem. 2003, 42, 5483-5485; (b) Catalano, V. J.; Moore, A. L., Inorg. Chem. 2005, 44, 6558-6566; (c) Samantaray, M. K.; Pang, K.; Shaikh, M. M.; Ghosh, P., Inorg. Chem. 2008, 47, 4153-4165.94. (a) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H., J. Am. Chem. Soc. 2002, 124, 4954-4955; (b) VanVeldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H., J. Am. Chem. Soc. 2005, 127, 6877-6882; (c) Malcolmson, S. J.; Meek, S. J.; Sattely, E. S.; Schrock, R. R.; Hoveyda, A. H., Nature 2008, 456, 933-937.

20Palladium(II) catalysts containing pyridyl-functionalized NHC donor ligands have found

important applications in cross-coupling reactions in the formation of C–C and C–N bonds.2d

Among all of the donor-functionalized NHC ligand, the amino (NH)-functionalized NHC

ligand is an important class of ligand system as it has a potential amphoteric character of the

basic carbene ligand and the acidic NH group (Figure 1.12). Arnold and co-workers reported the

coordination chemistry of such an NHC ligand with a secondary amine and an anionic amido

donor to lanthanide metals.96 Douthwaite reported the first primary amine-functionalized NHC

ligand on palladium(II) and silver(I),97 and a pincer-type C–NH–C ligand on palladium(II) as

well.98 Busetto reported the synthesis of silver(I) complexes with a protected NH functional

group tethered to the NHC ligand.99 Fryzuk reported rhodium(I) complexes100 and a Grubbs-like

ruthenium(II) complex containing an aniline-type nitrogen donor functionalized on the NHC

ligand.101 He showed that the hemilabile amine arm of the NHC donor did not improve catalytic

activity of ring opening metathesis polymerization reactions (ROMP) using their ruthenium(II)

complexes. Luo and co-workers reported the use of the anilido-type C–N–C pincer ligand on

palladium(II).102 More recently, Cross and co-workers reported palladium(II),103 platinum(II),103

ruthenium(II),104 rhodium(III)104 and iridium(III)104 complexes of bidentate or tridentate C–N or

C–N–C donor ligand with aniline-type NH and anilido-type donor. There are still no important

applications of these complexes to date in catalysis, however.

95. Hauwert, P.; Boerleider, R.; Warsink, S.; Weigand, J. J.; Elsevier, C. J., J. Am. Chem. Soc. 2010, 132, 16900-16910.96. Liddle, S. T.; Edworthy, I. S.; Arnold, P. L., Chem. Soc. Rev. 2007, 36, 1732-1744.97. Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R.; Houghton, J.; Kariuki, B. M.; Simonovic, S., Dalton Trans. 2004, 3528-3535.98. (a) Douthwaite, R. E.; Houghton, J.; Kariuki, B. M., Chem. Commun. 2004, 698-699; (b) Houghton, J.; Dyson, G.; Douthwaite, R. E.; Whitwood, A. C.; Kariuki, B. M., Dalton Trans. 2007, 3065-3073.99. Busetto, L.; Cassani, M. C.; Femoni, C.; Macchioni, A.; Mazzoni, R.; Zuccaccia, D., J. Organomet. Chem. 2008, 693, 2579-2591.100. Jong, H.; Patrick, B. O.; Fryzuk, M. D., Can. J. Chem. 2008, 86, 803-810.101. Jong, H.; Patrick, B. O.; Fryzuk, M. D., Organometallics 2011, 30, 2333-2341.102. Wei, W.; Qin, Y.; Luo, M.; Xia, P.; Wong, M. S., Organometallics 2008, 27, 2268-2272.103. Cross, W. B.; Daly, C. G.; Ackerman, R. L.; George, I. R.; Singh, K., Dalton Trans. 2011, 40, 495-505.104. Cross, W. B.; Daly, C. G.; Boutadla, Y.; Singh, K., Dalton Trans. 2011, 40, 9722-9730.

21

Figure 1.12. Structures of some metal complexes containing an amino (NH)-functionalized

NHC ligand.

1.4 Thesis Goals

The goal of the present research is to develop new catalyst systems that mimic the highly

active ruthenium(II) based catalysts containing phosphine-amine ligands (P–NH2). The new

catalyst systems will have the features required for bifunctional catalysis using the “NH effect”;

notably a highly active metal-hydride and a protic amine pair. Replacing the phosphine donor on

the P–NH2 ligand with an N-heterocyclic carbene donor, leading to a primary-amino

functionalized N-heterocyclic carbene ligand (C–NH2), will allow a comparison of their

activities in the H2-hydrogenation of polar bonds. The mechanisms of action for ketone

hydrogenation will be studied in detail. Throughout all of the chapters, Dr. Alan Lough collected

all of the X-ray crystallographic data and solved all of the structures for publication purposes.

Our first research direction is to investigate the synthesis of amino-functionalized

imidazolium salts as precursor for the C–NH2 ligand. Results obtained from past research in our

group and in the recent literature99 suggested that such a synthesis and subsequent complexation

to late transition metals is indeed difficult. We turned to the synthesis of nitrile-functionalized

imidazolium salts, in hope that the nitrile-functionalized group can be reduced to a primary

amine when the N-heterocyclic carbene donor is coordinated to the metal. The synthesis of a

N

NPh

nPr

NPd

ClClHH

N

NN

N

NnBu nBu

Pd

Cl

NN

Rh+ N

H N N

N Ru

PMe3

Ph

H

Ir

NN

NI

HH

NN

NSm

N(SiMe3)2

N(SiMe3)2

22library of nitrile-functionalized imidazolium salts (Chapter 2) and the coordination chemistry of

the nitrile-functionalized N-heterocyclic carbene (C–CN) on Ag, Rh, Ru (Chapter 2), Pd and Pt

(Chapter 3) were achieved. These materials have been described in articles in Organometallics

in the years 2009105 (Chapter 2) and 2010106 (Chapter 3).

The reduction of the nitrile-functionalized salt was achieved in the presence of nickel(II) and

reducing agents, leading to the first nickel(II) complex containing the primary-amino

functionalized (C–NH2) ligand. The C–NH2 ligand on this nickel(II) complex can be

transmetalated to late transition metals such as ruthenium(II) and osmium(II). All of these are

described in Chapter 4. This reaction generates active ruthenium(II) catalysts for the transfer

hydrogenation of acetophenone in basic 2-propanol, and the H2-hydrogenation of a variety of

polar double bonds under very mild conditions. The catalytic results pertaining to these catalysts

are also described in the same chapter. The materials including the synthesis of the first nickel(II)

complex containing such a C–NH2 ligand, and the catalytic results of the transfer hydrogenation

reactions have been published in Organometallics in 2009 as a full article.107 The results for H2-

hydrogenation of polar double bonds have been published in Chemical Communications in

2010.108

We are interested in studying the mechanism of action in the H2-hydrogenation of ketones

using the ruthenium(II) catalyst described in Chapter 4 that contains the C–NH2 ligand and an η6-

arene ligand. Chapter 5 describes our detailed experimental studies of this system in ketone

hydrogenation. The cationic hydride-amine complex of this ruthenium(II) complex was found to

be inactive during catalysis, and we showed that the N–H group in this system is not required for

catalysis. We compared the energies by computational studies of the catalytic cycles involving

the outer-sphere bifunctional and the inner-sphere mechanisms, and proposed an inner-sphere

mechanism based on our findings. These studies have been published in Organometallics in

2011 as a full article.109

We are also interested to compare the diagonal relationship between ruthenium(II) and

iridium(III) in the H2-hydrogenation of ketones, and to study the donor properties of phosphines

versus N-heterocyclic carbene ligands in catalysis. Chapter 6 describes our detailed studies of the

105. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 853-862.106. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2010, 29, 570-581.107. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 6755-6761.108. O, W. W. N.; Lough, A. J.; Morris, R. H., Chem. Commun. 2010, 46, 8240 – 8242.109. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2011, 30, 1236-1252.

23mechanism of action of ketone hydrogenation catalyzed by a ruthenium(II) catalyst described in

Chapter 4 containing a C–NH2 ligand and a pentamethylcyclopentadienyl ligand. The

structurally similar iridium(III) complex and its catalytic activity were also described. A similar

cationic hydride-amine complex of iridium(III) complex was isolated, but we found that this is

not responsible for the catalytic activity that was observed. We were surprised to find that both

systems undergo an alcohol-assisted outer-sphere bifunctional mechanism, and our computation

studies suggested the operation of an unprecedented iridium(I) intermediate, which is formed

from hydride migration to the pentamethylcyclopentadienyl ligand, is the active species during

catalysis. We also studied the catalytic activity in ketone hydrogenation of the ruthenium(II) and

the iridium(III) catalysts containing the P–NH2 ligand and compared to its C–NH2 counterpart.

These results have been submitted for publication as a full article.110

110. O, W. W. N.; Lough, A. J.; Morris, R. H., Submitted 2011.

24Chapter 2: Synthesis and Characterization of Nitrile-Functionalized

N-Heterocyclic Carbenes and Their Complexes of Silver(I),

Rhodium(I) and Ruthenium(II)

2.1 Abstract

A series of unsymmetrical nitrile-functionalized imidazolium salts were synthesized by N-

alkylation and N-arylation of 2-cyanophenylimidazole. These imidazolium salts were used to

synthesize nitrile-functionalized N-heterocyclic carbene (C–CN) complexes of silver(I), all of

which were fully characterized by spectroscopic means. The compound bis[1-(2-cyanophenyl)-3-

methylimidazol-2-ylidene]silver(I) tetrafluoroborate (2a) was structurally characterized by a X-

ray diffraction study. Interestingly, the preparation of the silver(I) carbene complex using 3-

(cyanomethyl)-1-(2-cyanophenyl)-imidazolium hexafluorophosphate (1b) and excess silver(I)

oxide leads to the formation of the desired bis-carbene complex, and the bis-carbene complex

with hydrolyzed cyanomethyl groups on the ligands. The selectivity in hydrolysis of the

cyanomethyl group over the cyanophenyl group on the ligand, as evident from the NMR data,

suggests that the process must be mediated by silver(I) centers. The use of an N-heterocyclic

carbene complex of silver(I) as a carbene transfer reagent was demonstrated by the reaction of 2a

with [Rh(cod)Cl]2 and [Ru(p-cymene)Cl2]2, respectively. The crystal structures of the dimeric

complexes, bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-(η4-1,5-cyclooctadiene)-

rhodium(I)] tetrafluoroborate (3) and bis[chloro(1-(2-cyanophenyl)-3-methylimidazol-2-

ylidene)-(η6-p-cymene)ruthenium(II)] tetrafluoroborate (4) showed that the nitrile nitrogen and

the carbene carbon of the C–CN ligand were bridged to two different metal centers, with a slight

distortion of the M–N≡C (M = Rh, Ru) bond angles.

2.2 Introduction

The use of N-heterocyclic carbenes (NHC) as ligands in homogeneous catalysis has been

extensively explored in the past decades because of the higher stability and reactivity they impart

*Reproduced in part with permission from O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 853-862. Copyright 2009 American Chemical Society.1. (a) Herrmann, W. A., Angew. Chem. Int. Ed. 2002, 41, 1290-1309; (b) Cui, X. H.; Burgess, K., Chem. Rev. 2005, 105, 3272-3296; (c) Hahn, F. E.; Jahnke, M. C., Angew. Chem. Int. Ed. 2008, 47, 3122-3172; (d) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676; (e) Vougioukalakis, G. C.; Grubbs, R. H., Chem. Rev. 2010, 110, 1746-1787.

25to homogeneous catalysts and their lower toxicity relative to phosphine ligands.1 The carbene

ligands, in particular, imidazol-2-ylidene-type ligands isolated by Arduengo and co-workers,2

have comparable or even stronger donor capacity compared to phosphine ligands, and are

capable of stabilizing metal centers with different oxidation states.3 With different synthetic

routes reported for these imidazolium salt precursors,4 the steric bulk of the ligand can be tuned

either on the imidazole backbone, or on the N,N-substituted groups. This is beneficial in order to

tune the activity and selectivity of a catalyst.

N-heterocyclic carbenes are viewed not only as spectator monodentate ligands in

homogeneous catalysis, but also, when suitably functionalized at nitrogen of the imidazolylidene

ring, as useful building blocks in the design of highly active homogeneous catalysts for various

important chemical transformations.5 These donor-functionalized NHC ligands show

coordination versatility when complexed to metal centers, and more importantly, provide ligand-

metal bifunctionality in small molecule activation.6

Our group has been interested in the hydrogenation of polar multiple bonds including ketones,

imines and nitriles catalyzed by ruthenium(II)7 and iron(II)8 based systems. In the continuous

pursuit of active catalysts for polar bond hydrogenation, we are interested in the use of N-

heterocyclic carbene ligands to enhance catalytic activities, so as to replace traditional phosphine

donors in the construction of highly active catalysis. From our initial report on the synthesis of

coordinatively unsaturated hydridoruthenium(II) NHC systems,9 we are interested in

constructing new donor-functionalized NHC ligands that would assist in the ligand-metal

bifunctional catalysis involved the action of M–H/H–X (X = N, O) in the hydrogenation of polar

2. (a) Kliegman, J. M.; Barnes, R. K., J. Org. Chem. 1970, 35, 3140-3143; (b) Arduengo, A. J.; Harlow, R. L.; Kline, M., J. Am. Chem. Soc. 1991, 113, 361-363; (c) Arduengo, A. J.; Krafczyk, R.; Schmutzler, R.; Craig, H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M., Tetrahedron 1999, 55, 14523-14534; 3. (a) Crudden, C. M.; Allen, D. P., Coord. Chem. Rev. 2004, 248, 2247-2273; (b) Scott, N. M.; Nolan, S. P., Eur. J. Inorg. Chem. 2005, 1815-1828; (c) Leuthausser, S.; Schwarz, D.; Plenio, H., Chem. Eur. J. 2007, 13, 7195-7203; (d) Fantasia, S.; Petersen, J. L.; Jacobsen, H.; Cavallo, L.; Nolan, S. P., Organometallics 2007, 26, 5880-5889; (e) Fey, N.; Haddow, M. F.; Harvey, J. N.; McMullin, C. L.; Orpen, A. G., Dalton Trans. 2009, 8183-8196; (f) Gusev, D. G., Organometallics 2009, 28, 763-770; (g) Gusev, D. G., Organometallics 2009, 28, 6458-6461; (h) Droge, T.; Glorius, F., Angew. Chem. Int. Ed. 2010, 49, 6940-6952.4. (a) Bon, R. S.; deKanter, F. J. J.; Lutz, M.; Spek, A. L.; Jahnke, M. C.; Hahn, F. E.; Groen, M. B.; Orru, R. V. A., Organometallics 2007, 26, 3639-3650; (b) Benhamou, L.; Chardon, E.; Lavigne, G.; Bellemin-Laponnaz, S.; Cesar, V., Chem. Rev. 2011, 111, 2705-2733 and references therein.5. (a) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (b) Kuhl, O., Chem. Soc. Rev. 2007, 36, 592-607; (c) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (d) Poyatos, M.; Mata, J. A.; Peris, E., Chem. Rev. 2009, 109, 3677-3707; (e) Corberan, R.; Mas-Marza, E.; Peris, E., Eur. J. Inorg. Chem. 2009, 1700-1716.6. Liddle, S. T.; Edworthy, I. S.; Arnold, P. L., Chem. Soc. Rev. 2007, 36, 1732-1744.

26bonds.10 The nitrile group, when hydrogenated at a late transition metal center, could produce a

H–M–NH2CH2– (M = Ru, Os, Rh or Ir) group known to be very effective at the hydrogenation

of ketones and imines.10c, 11

Figure 2.1. Nitrile-functionalized imidazolium salts 1a-1f.

In this chapter, we report the synthesis and characterization of a series of nitrile-

functionalized imidazolium salts (Figure 2.1), and their corresponding metal complexes of

silver(I), rhodium(I) and ruthenium(II) containing such a NHC ligand.12 Although an analogous

nitrile-functionalized NHC (C–CN) complex of palladium(II) was reported by Dyson and co-

workers, the nitrile moiety on the ligand (Figure 2.2) was remote from the metal center.13 More

recently, an intramolecular C–H bond activation of the CH2CN group of a nitrile-functionalized

NHC ligand on nickel(II) was reported by Chetcuti and Veiros forming new nickelacycles

(Figure 2.2).14 The nitrile group on these new ligands, on the other hand, shows coordination

versatility and reactivity with metal centers. The hydrolysis of the nitrile-functionalized carbene

ligand mediated by silver(I) centers is reported here.

7. (a) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2002, 124, 15104-15118; (b) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529; (c) Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579; (d) Guo, R. W.; Elpelt, C.; Chen, X. H.; Song, D. T.; Morris, R. H., Chem. Commun. 2005, 3050-3052; (e) Li, T.; Bergner, I.; Haque, F. N.; Iuliis, M. Z.-D.; Song, D.; Morris, R. H., Organometallics 2007, 26, 5940-5949.8. Morris, R. H., Chem. Soc. Rev. 2009, 38, 2282-2291 and references therein.9. Abdur-Rashid, K.; Fedorkiw, T.; Lough, A. J.; Morris, R. H., Organometallics 2004, 23, 86-94.10. (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S., J. Org. Chem. 2001, 66, 7931-7944; (b) Clapham, S. E.; Hadzovic, A.; Morris, R. H., Coord. Chem. Rev. 2004, 248, 2201-2237; (c) Ikariya, T.; Murata, K.; Noyori, R., Org. Biomol. Chem. 2006, 4, 393-406.11. (a) Ito, M.; Ikariya, T., Chem. Commun. 2007, 5134-5142; (b) Kuwata, S.; Ikariya, T., Dalton Trans. 2010, 39, 2984-2992; (c) Ikariya, T., Bull. Chem. Soc. Jpn. 2011, 84, 1-16.12. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 853-862.13. Fei, Z.; Zhao, D.; Pieraccini, D.; Ang, W. H.; Geldbach, T. J.; Scopelliti, R.; Chiappe, C.; Dyson, P. J., Organometallics 2007, 26, 1588-1598.

N

N N

N

N N RX

2'-PyCH2-2'-Py

-+

CH3CH2CN

R X

CH(CH3)Ph

BF4 (1a)

CH2CH2(3'-C9H7)

PF6 (1b)PF6 (1c)PF6 (1d)BF4 (1e)BF4 (1f)

27

Figure 2.2. Nitrile-functionalized N-heterocyclic carbene (C–CN) complexes of palladium(II)

(left) and nickel(II) (right).


2.3.1 Synthesis of Imidazolium Salt Precursors. Initial attempts utilized the standard protocol

for imidazolium salt synthesis starting from glyoxal and 2-aminobenzonitrile to synthesize 1,3-

bis(2-cyanophenyl)imidazolium halide. These failed because the nucleophilic character of the

amine-nitrogen of 2-aminobenzonitrile is diminished due to the presence of an ortho-cyano

group and so did not condense with glyoxal to yield the desired glyoxal diimine, even under

templating conditions in the presence of nickel(II) or zinc(II) cations.2a,2c We, therefore,

developed a synthesis of unsymmetrical imidazolium salts using the N-alkylation and N-arylation

of a substituted imidazole. The starting substituted imidazole, 2-cyanophenylimidazole, is

conveniently prepared in a large scale with very good yields using literature methods.15 The

syntheses of the new imidazolium salts were conducted by means of electrophilic alkylation with

trimethyloxonium tetrafluoroborate (Meerwein’s salt) to give 1a and SN2 reactions with

bromoacetonitrile, picolyl chloride and 3-(2-bromoethyl)indene to yield 1b, 1c and 1f,

respectively, in good yields (Schemes 2.1-2.3). N-alkylation using a secondary alkyl bromide is

slow giving 1e in low yield (Scheme 2.3). N-Arylation of 2-cyanophenylimidazole with phenyl

halides, on the other hand, did not proceed, even at elevated temperatures.16

14. Oertel, A. M.; Freudenreich, J.; Gein, J.; Ritleng, V.; Veiros, L. F.; Chetcuti, M. J., Organometallics 2011, 30, 3400-3411.15. (a) Johnson, A. L.; Kauer, J. C.; Sharma, D. C.; Dorfman, R. I., J. Med. Chem. 1969, 12, 1024-1028; (b) Ren, L.; Chen, A. C.; Decken, A.; Crudden, C. M., Can. J. Chem. 2004, 82, 1781-1787. 16. (a) Chan, B.; Chang, N.; Grimmett, M., Aust. J. Chem. 1977, 30, 2005-2013; (b) Harlow, K. J.; Hill, A. F.; Welton, T., Synthesis 1996, 697.

N NNN

NNN N

PdCl ClNi

N N RH

N

R = CH3, 2,4,6-(CH3)3C6H2 (Mes)n = 2-5

n-1

Chetcuti and VeirosDyson

28Under similar conditions reported in the literature for the preparation of 2'-pyridyl-substituted

imidazolium salts,17 compound 1d was prepared in 54% yield starting from 2-bromopyridine

(Scheme 2.3). The crude halide salts of 1b to 1f have limited solubility in most organic solvents,

except for water and dimethylsulfoxide (DMSO). Counteranion metathesis with NH4PF6 was

therefore performed in water to improve the solubility of the salts. In general, these

hexafluorophosphate and tetrafluoroborate salts were soluble in alcohols, acetonitrile, and water,

but not in chlorinated solvents.

Scheme 2.1. Synthesis of the Imidazolium Salt 1a and its Ag(I), Rh(I) and Ru(II) Complexes 2a,

3 and 4.

Scheme 2.2. Synthesis of Imidazolium Salt 1b and the Ag(I) complexes 2b and 2e.

17. (a) Tulloch, A. A. D.; Danopoulos, A. A.; Winston, S.; Kleinhenz, S.; Eastham, G., Dalton Trans. 2000, 4499-4506; (b) Chen, J. C. C.; Lin, I. J. B., Organometallics 2000, 19, 5113-5121.

N

N N CH3

BF4

NN

NCH3

BF4Ag

NN

NCH3

(BF4)2

1.5 Ag2O

(CH3)3O BF4CH3CN, rt

1.2 [Rh(cod)Cl]2

CH3CN, rt

N

N N

AgBF4

RhN

NN

RhN

NN

H3C

CH3

+

+

+ +

+

1a

2a3

Ru

ClN

N

N

H3C Ru

ClN

N

N

CH3

+

+(BF4)2

[Ru(p-cymene)Cl2]2

CH3CN, rt

AgBF4

∆ , CH3CN

4

N

N N

1bN

N N

N

PF6

NN

NPF6Ag

NN

NPF6

N N

NN

NAg

NN

NH2N NH2

+

O O

2e2b

BrCH2CN

H2O

NH4PF6

1.5 Ag2O

∆ , CH3CN

∆ , CH3CN

+ -

+- -

29Scheme 2.3. Synthesis of Imidazolium Salts 1c to 1f and the Ag(I) Complexes 2c and 2d.

These new imidazolium salts were unambiguously characterized by NMR spectroscopy. The

formation of 1a - 1f was indicated by a singlet in the 1H NMR spectra in the region between δ

9.6 and 10.6 ppm due to the presence of the acidic hydrogen attached to the ipso-carbon C2. The

presence of nitrile groups in the imidazolium salts 1a - 1d was signalled by a peak at about 2200

cm-1 in the IR-spectra. In addition, the structures of 1a and 1b (Figures 2.3 and 2.4) have been

structurally characterized by a X-ray diffraction study. The bond distances and angles are in the

expected range compared to those of known imidazolium salts, for example 1,3-bis(2,4,6-

trimethylphenyl)imidazolium chloride ([IMesH]Cl),18 and the bond distances in 1a are also

similar to those of 1-(4-cyanophenyl)-3-methylimidazolium.19

Several attempts to isolate the free carbene of 1a by treating it with KH or KN(SiMe3)2 in

THF solutions at -78 ºC failed. Isolation of the free carbene was apparently difficult due to its

reactivity toward its own electrophilic nitrile functionality.

18. Cole, M. L.; Junk, P. C., Crystengcomm 2004, 6, 173-176.19. Hatzidimitriou, A.; Gourdon, A.; Devillers, J.; Launay, J. P.; Mena, E.; Amouyal, E., Inorg. Chem. 1996, 35, 2212-2219.

N

N N

N

N NN

N

N N

N

PF6PF6

1c 1d

N

Br

NCl

∆ , EtOHNaHCO3. HCl

NH4BF4 H2ONH4PF6 H2O

1.5 Ag2O ∆ , CH3CN 1.5 Ag2O ∆ , CH3CN

[Ag(C-CN)]2(PF6)2, 2c [Ag(C-CN)]2(PF6)2, 2d

+ - +

NH4PF6 H2O

N

N NBF4

+

N

N NBF4

+

--

Br

∆ , CH3CN

∆

NH4BF4 H2O

Br

∆ , CH3CN

1e

1f

30


counteranion and hydrogens have been omitted for clarity. Selected bond distances (Å) and bond

angles (deg): C(1)-N(1), 1.340(3); C(1)-N(2), 1.324(3); C(2)-C(3), 1.342(3); C(11)-N(3),

1.139(3); N(1)-C(1)-N(2), 108.2(2).

Figure 2.4. ORTEP diagram of 1b depicted with thermal ellipsoids at 30% probability. The


angles (deg): C(1)-N(1), 1.342(5); C(1)-N(2), 1.328(5); C(2)-C(3), 1.349(6); C(12)-N(4),

1.134(6); C(5)-N(3), 1.142(6); N(1)-C(1)-N(2), 107.8(4).

2.3.2 Nitrile Functionalized N-Heterocyclic Carbene Complexes of Silver(I). Ever since the

first report by Wang and Lin,20 N-heterocyclic carbene complexes of silver(I) have served as

convenient carbene transfer reagents, providing a wide range of platinum metal group

20. Wang, H. M. J.; Lin, I. J. B., Organometallics 1998, 17, 972-975.21. (a) Garrison, J. C.; Youngs, W. J., Chem. Rev. 2005, 105, 3978-4008; (b) Lin, I. J. B.; Vasam, C. S., Coord. Chem. Rev. 2007, 251, 642-670; (c) Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B., Chem. Rev. 2009, 109, 3561-3598.

31complexes.21 These silver(I)-NHC complexes were prepared by the treatment of the imidazolium

salt precursors with mildly basic silver(I) oxide or silver(I) carbonate,17a normally under mild

conditions. Given the ease of their preparation, their relative stability toward air and moisture,

and their structural diversity, we were prompted to prepare analogous silver(I) complexes

bearing nitrile-functionalized N-heterocyclic carbene ligands.

The silver(I) complexes, 2a-2d, were prepared by the reaction of excess silver(I) oxide with

the imidazolium salts 1a-1d, respectively, under reflux for overnight with protection from light

(Schemes 2.1-2.3). Stirring the aforementioned solutions at room temperature did not work

efficiently. In addition, an excess of silver(I) oxide, preferably 1.5 equiv with respect to the

imidazolium salt, is required for the successful generation of these bis-silver(I)-NHC complexes.

A full conversion under the same reaction conditions could not be achieved if a stoichiometric

amount of base was used. The use of molecular sieves was crucial for obtaining a pure product

by preventing the hydrolysis of the nitrile group in the presence of silver hydroxide and water

(vide infra).

The formation of these silver(I) complexes was established by observing a sharp singlet above

182 ppm in the 13C{1H} NMR spectra which was assigned to the carbene carbon attached to the

silver center (Ag–C). No one-bond coupling 1J(107Ag-13C) or 1J(109Ag-13C) was observed, even at

-40 ºC for 2a in acetonitrile-d3 solution.21a, 21c This may be the result of a rapid exchange of

carbene ligands between silver ions. On the other hand, the absence of a peak in the region of δ

9.6-10.6 ppm in the 1H NMR spectra further suggested full conversion to silver(I) NHC

complexes.

The silver(I) complex, [Ag(C-CN)2]BF4 (2a) has been structurally characterized by use of X-

ray diffraction (Figure 2.5). The complex crystallizes in the monoclinic space group P21/n with

four units residing in the unit cell. The structure shows a slightly distorted geometry from

linearity about the silver(I) center, and the C–Ag–C bond angle of 171.1(2)º is smaller than those

of typical [Ag(NHC)2]+ complexes, at around 174-177º. The average Ag–C distance is 2.095 Å,

which is in the expected range of typical [Ag(NHC)2]+ complexes. The decrease in the C–N bond

lengths C(1)-N(1) and C(1)-N(2) and the bond angle N(1)-C(1)-N(2) in the imidazol-2-ylidene

22. (a) Paas;, M.; Wibbeling;, B.; Fröhlich;, R.; Hahn, F. E., Eur. J. Inorg. Chem. 2006, 2006, 158-162; (b) Samantaray, M. K.; Pang, K.; Shaikh, M. M.; Ghosh, P., Inorg. Chem. 2008, 47, 4153-4165; (c) Liao, C. Y.; Chan, K. T.; Chiu, P. L.; Chen, C. Y.; Lee, H. M., Inorg. Chim. Acta 2008, 361, 2973-2978.

32ring compared to the imidazolium salt suggests an increase in p-character at the carbene

carbon.17a, 20-22

In addition, the phenyl rings are twisted with respect to the imidazole rings in opposite

enantiomeric configurations with dihedral angles of 43.18º and 51.05º, in order to facilitate

stacking of phenyl and imidazole rings in the crystal lattice, with the contact distance between

them being 3.40 Å, which is comparable to the sum of van der Waals radius of carbon atoms

(Figure 2.5).



angles (deg): Ag(1)-C(1), 2.094(5); Ag(1)-C(4), 2.095(5); C(1)-N(1), 1.359(6); C(1)-N(2),

1.362(6); C(13)-N(5), 1.140(7); C(1)-Ag(1)-C(4), 171.1(2); N(1)-C(1)-N(2), 104.4(4).

The complexes 2c and 2d showed different structural motifs compared to 2a. We would

expect the structures of these compounds would be similar to those of other pyridyl-

functionalized N-heterocyclic carbene complexes of silver(I).17a, 23 However, the analytical data

(NMR, Fourier transform infrared (FT-IR), and elemental analysis) suggest the presence of a

[Ag(NHC)]PF6 unit, which could exist in a monomeric, dimeric, or trimeric structure. Although

crystals suitable for X-ray diffraction were not obtained successfully, the structures can be

partially assigned on the basis of NMR data. Only one set of signals are present in the 1H NMR 23. (a) Catalano, V. J.; Malwitz, M. A., Inorg. Chem. 2003, 42, 5483-5485; (b) Catalano, V. J.; Malwitz, M.

A.; Etogo, A. O., Inorg. Chem. 2004, 43, 5714-5724; (c) Catalano, V. J.; Moore, A. L., Inorg. Chem. 2005, 44, 6558-6566; (d) Catalano, V. J.; Etogo, A. O., J. Organomet. Chem. 2005, 690, 6041-6050.

33spectra, indicative of a symmetric single component complex. A monomeric structure is highly

unlikely, as the C–Ag–NPy angle will be bent away from linearity, if the pyridyl group were to

bond to the metal center. A trimeric structure is not possible, as metal-metal interactions of the

silver(I) clusters will give rise to extensive Ag-C couplings at the carbene carbon in the 13C{1H}

NMR spectrum. Only a sharp singlet was observed in our system at δ 183 ppm. This signal is

more downfield than those of silver(I) cluster systems, such as [Ag3((pyCH2)2imid)3](BF4)3 and

[Ag3((quinCH2)2imid]3](BF4)3 (py = 2'-pyridyl; quin = 2'-quinolyl; imid = imidazol-2-

ylidene).23a, 23b Dimeric structures are most probable, with either the nitrile or the pyridyl group

bound to the silver(I) center to produce a dication with a 10- or 12-membered

macrometallocyclic ring. Silver(I)-NHC complexes forming a 12-membered ring

macrometallocycle are known, at least with donor-functionalized NHC ligands of alkylated

amides22b, 24 and pyrazoles.25 Bridging via the nitrile group on the carbene is not likely because

the wavenumbers of the nitrile stretch of these compounds and their imidazolium precursors

observed in the IR spectra are comparable (see the Section 2.5). The only additional binding site

is through the pyridyl group of the ligand. Possible structures are given in Figure 2.6, with each

silver(I) center bonding to the carbene carbon and nitrogen (2c-1, 2d-1), or with one silver(I)

center bonding to two carbene carbons, and the others bonding to two nitrogens (2c-2, 2d-2),

similar to those reported with pyrazole-functionalized NHC ligands.25

Figure 2.6. Proposed structures of Ag(I) complexes 2c and 2d forming 12- and 10 membered

rings, respectively.

24. Legault, C. Y.; Kendall, C.; Charette, A. B., Chem. Commun. 2005, 3826-3828.25. (a) Chiu, P. L.; Chen, C. Y.; Lee, C.-C.; Hsieh, M.-H.; Chuang, C.-H.; Lee, H. M., Inorg. Chem. 2006, 45, 2520-2530; (b) Zhou, Y. B.; Zhang, X. M.; Chen, W. Z.; Qiu, H. Y., J. Organomet. Chem. 2008, 693, 205-215.

N NN

N

N NN

N

Ag (PF6)2

2c-1

(PF6)2

N NN

N

N N N

N

Ag Ag

Ag

(PF6)2

N NN

N

N N N

N

NNN

N

Ag Ag

NNN

N

AgAg

(PF6)2

2c-2

2d-1 2d-2

+ + + +

++

+ +

- -

--

342.3.3. Hydrolysis of Nitrile groups on the Silver(I) Complex 2b. In the preparation of the

silver(I) complex using the imidazolium salt 1b, a mixture of products 2b and 2e was always

observed, even when molecular sieves were used in the syntheses. The appearance of two broad

peaks at δ 6.12 and 6.49 ppm in the 1H NMR spectrum of the compounds in acetonitrile-d3

suggested the presence of an amide group (Figure 2.7c), and this is further confirmed by their

disappearance upon the addition of D2O to the NMR sample.

We initially believed that these peaks were due to the presence of acetamide formed by the

hydrolysis of acetonitrile during the course of reaction, as similar peaks were observed in the

preparation of 2a without using molecular sieves. In order to identify these products that resulted

from hydrolysis, we attempted to synthesize acetamide under the same conditions that were used

in the preparation of 2a-2d. The 1H NMR (400 MHz) of the reaction mixture resulting from

refluxing a solution of acetonitrile, water, and silver(I) oxide in acetonitrile-d3 showed two broad

peaks at δ 6.03 and 6.64 ppm (Figure 2.7b). This was compared to the 1H NMR (400 MHz) of

pure acetamide in acetonitrile-d3, which gave two broad peaks at δ 6.18 and 6.51 ppm (Figure

2.7a). The peak separations of these amide-NH peaks are quite different for these compounds. In

particular, it is smaller in pure acetamide (0.33 ppm) than in the ones prepared from silver(I)

oxide (0.61 ppm). Even though the peak separation between the amido-protons of 2e are small

(0.37 ppm) like that of acetamide, the peak width of these protons are the smallest among all.

These observations suggest the NH2 group in 2e has a higher barrier to rotation about the C–N

bond compared to free acetamide. We postulate that a weak silver-oxygen electrostatic

interaction may contribute to the observed NMR behavior, and this could also explain the

smaller peak separation for acetamides prepared from silver(I) oxide when compared to pure

acetamide.

35

Figure 2.7. 1H NMR spectra (400 MHz) in the amide-NH region of (a) acetamide, (b) acetamide

prepared from hydrolysis of acetonitrile with silver oxide and water, and (c) 2e in acetonitrile-d3.

Further evidence for the formation of the hydrolyzed complex 2e is provided from NMR data

acquired from the reaction mixture. The appearance of new sets of aromatic peaks in the 1H

NMR spectrum suggests the formation of a new compound, whereas the integration of each

aromatic peak to each amido-proton is 1 to 1. A more diagnostic piece of evidence derived from

the 13C{1H} NMR spectrum is a peak at δ 169.4 ppm for the mixture in acetonitrile-d3, which

corresponds to the carbonyl carbon of the primary amide. In addition, all the aromatic signals in

the 13C{1H} NMR doubled up, except for the nitrile carbon attached to the methylene linker.

However, we do observe the formation of acetamide as minor broad peaks in the 1H NMR at δ

5.86 and 6.21 ppm in the sample in acetonitrile-d3. The new amido-NHC silver(I) complex 2e,

compared to alkylated amido-functionalized NHC complexes of silver(I),22b, 22c, 24 are not stable

in solutions and in solid state, even when protected from light, as facile decomposition takes

place. In an attempt to convert 2b to 2e by treating aqueous potassium hydroxide at room

temperature, the product decomposed readily after 2h of reaction.

We believe that the nitrile group attached to the methylene linker is preferentially hydrolyzed

over that of attached to the phenyl ring. The cyanophenyl and the carbonyl carbon of 2e were

36identified in the 13C{1H} NMR spectrum, and the assignment was further established by two-

dimensional 1H-13C HSQC and HMBC NMR experiments. In addition, under identical reaction

conditions in the preparation of 2a and 2b when molecular sieves were used, the amido-protons

were absent in 2a but not in 2b, even though hydrolysis can be promoted without the use of

molecular sieves in the preparation of 2a.

This selectivity is reversed compared to conventional base hydrolysis where the benzonitrile

is hydrolyzed more readily. This suggests the hydrolysis is mediated by the metal center. In fact,

as there are more degrees of freedom of the cyanomethyl group compared to the cyanophenyl

group, the nitrogen on the nitrile group can be activated by two silver(I) cations to facilitate

attack by the hydroxide ion on the electrophilic carbon, which leads to the formation of a six-

membered ring intermediate 2e-i (Scheme 2.4). A similar behavior was observed by Mao and co-

workers, when the nitrogen on the acetonitrile was activated by two silver(I) centers of a silver(I)

cryptate system, and thus underwent catalytic hydrolysis,26 although the nitrile was hydrolyzed

stoichiometrically by silver hydroxide in our system.

We propose that the hydrolysis occurs during the preparation of 2b according to Scheme 2.4.

The first equivalent of the imidazolium salt reacts with silver(I) oxide, leading to the formation

of the monocarbene complex 2b-i and silver hydroxide. Silver hydroxide and a second

equivalent of the imidazolium salt react to generate the more thermodynamically stable complex

2b.27 However, as water is generated and in the presence of silver(I) oxide, more silver

hydroxide is generated and this starts to hydrolyze the cyanomethyl group on the ligand, forming

the six-member ring intermediate 2e-i. Further hydrolysis lead to the final product 2e.

26. Luo, R.-S.; Mao, X.-A.; Pan, Z.-Q.; Luo, Q.-H., Spectrochim. Acta, Part A 2000, 56, 1675-1680.27. Hayes, J. M.; Viciano, M.; Peris, E.; Ujaque, G.; Lledos, A., Organometallics 2007, 26, 6170-6183.

37Scheme 2.4. Proposed Reaction Pathways to Hydrolysis of Ag(I) Complex 2b to 2e.

2.3.4. Nitrile Functionalized N-Heterocyclic Carbene Complex of Rhodium(I) and

Ruthenium(II). To demonstrate the use of a silver(I)-NHC complex as a carbene transfer

reagent, we reacted [Ag(C–CN)2]BF4 (2a) with [Rh(cod)Cl]2 and 1 equiv of AgBF4 in

acetonitrile, and [Ru(p-cymene)Cl2]2 and 1 equiv of AgBF4 in acetonitrile to afford 3 and 4 in

71% and 79% yields, respectively. These yellow complexes are very soluble in acetonitrile,

where they tend to react, and soluble in nitromethane and nitroethane, but only slightly soluble in

acetone, alcohols, and chlorinated solvents. Interestingly, both complexes crystallized as dimers

and were structurally characterized by X-ray diffraction (Figures 2.8 and 2.9).

In the solid state structure of 3 ([Rh(C–CN)(cod)]2(BF4)2, Figure 2.8), the structure shows a

slightly distorted square planar geometry about the rhodium(I) center. The Rh–C22d, 28 distance is

in the expected range for analogous compounds. The Rh–cod bond distances measured from the

centroid of the olefin are different with respect to its coordination sphere, the one trans to the

carbene (2.100 Å) being longer than the one trans to nitrile (2.016 Å). The carbene ligand should

impart a stronger trans influence compared to the nitrile group, and this is also seen in the

28. (a) Dastgir, S.; Coleman, K. S.; Cowley, A. R.; Green, M. L. H., Organometallics 2006, 25, 300-306; (b) Messerle, B. A.; Page, M. J.; Turner, P., Dalton Trans. 2006, 3927-3933; (c) Jong, H.; Patrick, B. O.; Fryzuk, M. D., Can. J. Chem. 2008, 86, 803-810; (d) Jimenez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A., Organometallics 2008, 27, 224-234; (e) Dyson, G.; Frison, J. C.; Simonovic, S.; Whitwood, A. C.; Douthwaite, R. E., Organometallics 2008, 27, 281-288; (f) Dyson, G.; Frison, J. C.; Whitwood, A. C.; Douthwaite, R. E., Dalton Trans. 2009, 7141-7151; (g) Praetorius, J. M.; Wang, R. Y.; Crudden, C. M., Eur. J. Inorg. Chem. 2009, 1746-1751; (h) Yu, X. Y.; Sun, H. S.; Patrick, B. O.; James, B. R., Eur. J. Inorg. Chem. 2009, 1752-1758.

Ag2O

-AgOH

xs AgOHH2O

NN

NAg

NN

NC N N

NN

N

N

xs AgOH

H2O

AgOH

- H2O, AgPF6CH3CN

1b

δ+

δ -AgO

HH2O

δ +δ -

NN

NAg

NH2

O δ -

2b-i

2e-i

1bN

N N

N

PF6+ -

NN

NAg

N

2b

NN

NPF6Ag

NN

N

N N

-

N CH3+

+

PF6

NN

NAg

NN

NH2N NH2

O O

2e

+ -+ +

+-

PF6-

PF6-

38olefinic bond distances of the cyclooctadiene ligand (C(5)-C(6)trans to carbene: 1.361(8) Å; C(1)-

C(2)trans to nitrile: 1.389(7) Å). On the other hand, the C(9)-N(1)-Rh(1) bond angle is bent away

from linearity at 172.0(5)º, indicating strain in the 14-membered Rh–C–N–Rh–C–N ring. The

dihedral angle between the phenyl ring and the imidazole group is 51.05º, and the traverses of

the skewed groups have the same chirality.


counteranions and hydrogens have been omitted for clarity. Selected bond distances (Å) and

bond angles (deg): Rh(1)-C(16), 2.040(5); Rh(1)-N(1), 2.064(4); Rh(1)-cod(trans to N)cent, 2.016;

Rh(1)-cod(trans to C)cent, 2.100; C(9)-N(1), 1.139(6); C(9)-N(1)-Rh(1), 172.0(5); C(16)-Rh(1)-

N(1), 89.9(2); N(1)-Rh(1)-cod(trans to N)avg, 160.6; N(1)-Rh(1)-cod(cis to N)avg, 91.15; C(16)-

Rh(1)-cod(trans to C)avg, 162.1; C(16)-Rh(1)-cod(cis to C)avg, 92.37.

The solid state structure of 4 ([Ru(p-cymene)(C–CN)Cl]2(BF4)2, Figure 2.9) shows two

ruthenium center that are bridged to the NHC and the nitrile group. The Ru–C distance is the

expected range for analogous half-sandwich compounds of ruthenium(II) containing an NHC

ligand.29 Again, the C(11a)-N(3a)-Ru(1a) bond angle is bent away from linearity at 173.7(6)º to

relieve the ring strain in a 14-membered Ru–C–N–Ru–C–N ring. The dihedral angle between

the phenyl ring and the imidazole group is 83.07º to facilitate coordination of both the nitrile and

the carbene to the metal centers.

39


counteranions and hydrogens have been omitted for clarity. Only one asymmetric unit is shown.

Selected bond distances (Å) and bond angles (deg): Ru(1a)-C(1a), 2.078(7); Ru(1a)-N(3a),

2.028(8); Ru(1a)-Cl(1a), 2.408(2); Ru(1a)-C(12a), 2.238(8); C(11a)-N(3a), 1.13(1); C(11a)-

N(3a)-Ru(1a), 173.3(6); C(1a)-Ru(1a)-N(3a), 84.9(3); C(1a)-Ru(1a)-Cl(1a), 90.9(2); N(3a)-

Ru(1a)-Cl(1a), 83.7(2).

Additional spectroscopic evidence supports the coordination of nitrile as well as the carbene

carbon. The 13C{1H} NMR of 3 in dichloromethane-d2 shows a doublet at δ 178.4 ppm (1JRh,C =

50.47 Hz), which is typical for most Rh(NHC) systems.22a, 28 A doublet is also located at δ 108.0

ppm (2JRh,C = 7.60 Hz) for the carbon on the nitrile group coordinated to rhodium(I). This

29. (a) Herrmann, W. A.; Kocher, C.; Goossen, L. J.; Artus, G. R. J., Chem. Eur. J. 1996, 2, 1627-1636; (b) Geldbach, T. J.; Laurenczy, G.; Scopelliti, R.; Dyson, P. J., Organometallics 2006, 25, 733-742; (c) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Toupet, L.; Castarlenas, R.; Fischmeister, C.; Dixneuf, P. H., Eur. J. Inorg. Chem. 2007, 2862-2869; (d) Ozdemir, I.; Demir, S.; Gurbuz, N.; Cetinkaya, B.; Toupet, L.; Bruneau, C.; Dixneuf, P. H., Eur. J. Inorg. Chem. 2009, 1942-1949.29. (e) Gandolfi, C.; Heckenroth, M.; Neels, A.; Laurenczy, G. b.; Albrecht, M., Organometallics 2009, 28, 5112-5121; (f) Horn, S.; Gandolfi, C.; Albrecht, M., Eur. J. Inorg. Chem. 2011, 2863-2868.

40coupling is small compared to ones in systems such as the pincer-type compound Rh(PCN)

(PhCN) (PCN = PiPr2CH2-2-(3,5-(CH3)2-C6H)-6-CH2NEt2, 2JRh,C = 19.1 Hz).30 The carbene

resonance was observed for 4 at 170.4 ppm in its 13C{1H} NMR in nitromethane-d3. Further, the

nitrile stretching frequency observed in the IR spectrum (2183 cm-1) is significantly lower than

that of the imidazolium salt (2283 cm-1). The nitrile stretch for 4, however, was not observed in

its IR spectrum.

2.4 Conclusion

We have reported the synthesis of unsymmetrical nitrile-functionalized imidazolium salts

from 2-cyanophenylimidazole. The reactions of these imidazolium salts with silver(I) oxide

yielded silver(I) carbene complexes 2a-2d. The preparations of these complexes were sensitive

to the presence of water. In particular, the reaction of 1b with excess silver(I) oxide in the

presence of molecular sieves leads to the formation of the desired bis-carbene complex, but also

leads to the hydrolysis of the cyanomethyl group of the carbene ligand. This is the first report of

the observation of a NHC complex of silver(I) with a primary-amido donor. The selectivity in

hydrolysis of cyanomethyl group over the cyanophenyl group suggests the process must be

mediated by silver centers. We have observed hindered rotation about the C–N bond of the

amide by means of NMR, and suggested that an interaction between the silver(I) center and the

oxygen of the amido-group was present.

The use of these N-heterocyclic carbene complexes of silver(I) as a carbene transfer reagent

was further demonstrated by the reaction of [Ag(C–CN)2]BF4 (2a) with [Rh(cod)Cl]2 and [Ru(p-

cymene)Cl2]2. This C–CN ligand has shown versatility in its coordination in 3 and 4. These

complexes with bridging carbene ligands crystallized as dimers where the nitrile on the ligand

and the carbene ligand were coordinated to two different metal centers.

30. Cohen, R.; Rybtchinski, B.; Gandelman, M.; Shimon, L. J. W.; Martin, J. M. L.; Milstein, D., Angew.Chem. Int. Ed. 2003, 42, 1949-1952.


2.5.1 General Considerations. All of the preparations and manipulations, except where

otherwise stated, were carried out under an argon or nitrogen atmosphere using standard

Schlenk-line and glovebox techniques. Dry and oxygen-free solvents were always used. The

syntheses of (2-cyanophenyl)imidazole15b, 3-(2-bromoethyl)indene31 and [Rh(cod)Cl]232 were

reported in the literature. All other reagents were purchased from commercial sources and were

used as received. Deuterated solvents were purchased from Cambridge Isotope Laboratories and

degassed and dried over activated molecular sieves prior to use. NMR spectra were recorded on a

Varian 400 spectrometer operating at 400 MHz for 1H, 100 MHz for 13C and 376 MHz for 19F.

The 1H and 13C NMR were measured relative to partially deuterated solvent peaks but are

reported relative to tetramethylsilane (TMS). All 19F chemical shifts were measured relative to

trichlorofluoromethane as an external reference. All infrared spectra were recorded on a Nicolet

550 Magna-IR spectrometer. The elemental analysis was performed at the Department of

Chemistry, University of Toronto, on a Perkin-Elmer 2400 CHN elemental analyzer. Samples

were handled under argon where it was appropriate. Single-crystal X-ray diffraction data were

collected using a Nonius Kappa-CCD diffractometer with Mo Kα radiation (λ = 0.71073 Å). The

CCD data were integrated and scaled using the Denzo-SMN package. The structures were solved

and refined using SHELXTL V6.1. Refinement was by full-matrix least-squares on F2 using all

data.

2.5.2. Synthesis of 1-(2-Cyanophenyl)-3-methylimidazolium Tetrafluoroborate (1a). A

Schlenk flask was charged with (2-cyanophenyl)imidazole (1.69 g, 10 mmol) and

trimethyloxonium tetrafluoroborate (Meerwein’s salt; 2.22 g, 15 mmol). Dry acetonitrile (20 mL)

was then added to the reaction mixture, for which a yellow color was observed. The solution was

stirred at ambient temperature for 2 h under argon, and the solvent was removed in vacuo. The

crude product was recrystallized with hot methanol to give a white crystalline solid. Yield: 2.45

g, 90%. 1H NMR (DMSO-d6, δ): 9.66 (s, 2-CH of imid., 1H), 8.27 (t, JHH= 1.84 Hz, 5-CH of

imid., 1H), 8.20 (dd, JHH = 1.03, 7.63 Hz, 3-CH of Ph, 1H), 8.03 (dt, JHH= 1.03, 8.83 Hz, 5-CH

of Ph, 1H), 8.00 (t, JHH = 1.84 Hz, 4-CH of imid., 1H), 7.88 (dd, JHH = 1.45, 8.83 Hz, 6-CH of

Ph, 1H), 7.86 (dt, JHH = 1.45, 7.63 Hz, 4-CH of Ph, 1H), 4.01 (s, CH3, 3H). 13C{1H} NMR

(DMSO-d6, δ): 137.7 (NCN), 136.1 (CPh), 134.9 (CPh), 134.3 (CPh), 131.1(CPh), 127.1(CPh), 124.1

31. Deppner, M.; Burger, R.; Alt, H. G., J. Organomet. Chem. 2004, 689, 1194-1211.32. Giordano, G.; Crabtree, R. H., Inorg. Synth. 1990, 28, 88-90.

42(Cimid.), 123.2 (Cimid.), 114.9 (CN), 108.4 (CPh), 36.1 (CH3). IR (KBr, cm-1): 2238 (v(CN)). MS

(ESI, methanol/water; m/z): 184.1 (M+). Anal. Calcd for C11H10BF4N3: C, 48.75; H, 3.72; N,

15.50. Found: C, 48.45; H, 3.74; N, 15.43.

2.5.3. Synthesis of 3-(Cyanomethyl)-1-(2-cyanophenyl)imidazolium Hexafluorophosphate

(1b). A two-necked Schlenk flask was charged with (2-cyanophenyl)imidazole (1.69 g, 10

mmol) in dry acetonitrile (20 mL). Bromoacetonitrile (1.80 g, 15 mmol) was added through a

syringe to the refluxing solution during the course of 0.5 h under argon. The reflux was

continued for 3.5 h, whereupon the bromide salt of the imidazolium precipitated out from the

reaction mixture. After the reaction mixture was cooled to ambient temperature, the white solids

were filtered and rinsed with diethyl ether. The crude bromide salt of the imidazolium was

dissolved in water (10 mL), and was added to a saturated aqueous solution (10 mL) of

ammonium hexafluorophosphate (2.45 g, 15 mmol). The white precipitate was then filtered,

rinsed with cold water, and recrystallized with hot ethanol to give a white crystalline solid.

Yield: 2.96 g, 84%. 1H NMR (DMSO-d6, δ): 9.87 (s, 2-CH of imid., 1H), 8.39 (t, JHH = 1.83 Hz,

4-CH of imid., 1H), 8.23 (t, JHH = 1.83 Hz, 5-CH of imid., 1H), 8.22 (dd, JHH = 1.37, 7.67 Hz, 3-

CH of Ph, 1H), 8.04 (dt, JHH = 1.37, 8.09 Hz, 5-CH of Ph, 1H), 7.92 (dd, JHH = 1.22, 8.09 Hz, 6-

CH of Ph, 1H), 7.87 (dt, JHH = 1.22, 7.67 Hz, 4-CH of Ph, 1H), 5.74 (s, CH2, 2H). 13C{1H} NMR

(DMSO-d6, δ): 138.9 (NCN), 136.0 (CPh), 134.9 (CPh), 134.4 (CPh), 131.4 (CPh), 127.3 (CPh),

124.2 (Cimid), 123.2 (Cimid), 115.0 (PhCN), 114.3 (CH2CN), 108.7 (CPh), 37.3 (CH2). IR (KBr,

cm-1): 2236 (v(CN)). MS (ESI, methanol/water; m/z): 209.1 (M+). Anal. Calcd for C12H9F6N4P:

C, 40.69; H, 2.56; N, 15.82. Found: C, 40.68; H, 2.51; N, 15.63.

2.5.4. Synthesis of 1-(2-Cyanophenyl)-3-(2-pyridinylmethyl)imidazolium Hexafluoro-

phosphate (1c). A solution of 2-picolyl chloride hydrochloride (1.23 g, 7.5 mmol) and

potassium carbonate (0.95 g, 11.3 mmol) in degassed 95% ethanol (10 mL) was stirred at

ambient temperature for 15 min under argon. The reddish solution was added through a syringe,

to a refluxing solution of (2-cyanophenyl)imidazole (0.846 g, 5 mmol) in degassed 95% ethanol

(10 mL). The solution was then refluxed for overnight under argon until a deep red color solution

was obtained. The solvent was removed in vacuo, and the residue was dissolved in water (10

mL) and filtered to remove any unreacted (2-cyanophenyl)imidazole. The aqueous solution

containing the crude chloride salt of the imidazolium salt was then added to a saturated aqueous

solution (10 mL) of ammonium hexafluorophosphate (1.22 g, 7.5 mmol). The red-brown

precipitate was then filtered, rinsed with cold water, recrystallized with hot ethanol and chilled at

43-78ºC to give a tan solid. Yield: 1.01 g, 50%. 1H NMR (DMSO-d6, δ): 9.92 (s, 2-CH of imid.,

1H), 8.60 (m, 6-CH of Py, 1H), 8.32 (t, JHH = 1.84 Hz, 5-CH of imid., 1H), 8.21 (dd, JHH = 1.53,

7.65 Hz, 3-CH of Ph, 1H), 8.12 (t, JHH = 1.84 Hz, 4-CH of imid., 1H), 8.03 (dt, JHH = 1.53, 7.80

Hz, 5-CH of Ph, 1H), 7.94 (dd, JHH = 1.11, 7.65 Hz, 6-CH of Ph, 1H), 7.92 (m, 4-CH of Py, 1H),

7.86 (dt, JHH = 1.11, 7.80 Hz, 4-CH of Ph, 1H), 7.57 (m, 3-CH of Py, 1H), 7.44 (m, 5-CH of Py,

1H), 5.73 (s, CH2, 2H). 13C{1H} NMR (DMSO-d6, δ): 152.9 (CPy), 149.6 (CPy), 138.1 (NCN),

137.5 (CPy), 136.2 (CPh), 134.9 (CPh), 134.4 (CPh), 131.2 (CPh), 127.3 (CPh), 123.9 (Cimid.), 123.7

(Cimid), 123.6 (CPy), 122.6 (CPy), 115.0 (CN), 108.7 (CPh), 53.6 (CH2). IR (KBr, cm-1): 2236

(v(CN)). MS (ESI, methanol/water; m/z): 261.1 (M+). Anal. Calcd for C16H13F6N4P: C, 47.30; H,

3.23; N, 13.79. Found: C, 47.03; H, 3.29; N, 13.22.

2.5.5. Synthesis of 1-(2-Cyanophenyl)-3-(2-pyridinyl)imidazolium Hexafluorophosphate

(1d). A 10 mL round-bottom flask was charged with (2-cyanophenyl)imidazole (0.846 g, 5

mmol) and 2-bromopyridine (1.19 g, 7.5 mmol), and was heated neat at 140ºC under argon for 1

day with vigorous stirring. The liquid was cooled down to give a deep red solid, which was

extracted with water and filtered through activated charcoal to give a bright red solution. The red

solution containing the crude bromide salt of the imidazolium salt was then added to a saturated

aqueous solution (10 mL) of ammonium hexafluorophosphate (1.22 g, 7.5 mmol). The red

precipitate was filtered, rinsed with cold water, and was recrystallized with hot ethanol and

chilled at -78ºC to give a red solid. Yield: 1.05 g, 54%. 1H NMR (DMSO-d6, δ): 10.63 (s, 2-CH

of imid., 1H), 8.83 (dd, JHH = 1.72, 2.12 Hz, 5-CH of imid., 1H), 8.72 (m, 3-CH of Py, 1H), 8.58

(dd, JHH = 1.72, 2.12 Hz, 4-CH of imid., 1H), 8.30 (m, 5-CH of Py, 1H), 8.26 (dd, JHH = 1.55,

8.06 Hz, 3-CH of Ph, 1H), 8.14 (m, 6-CH of Py, 1H), 8.08 (dd, JHH = 1.40, 7.52 Hz, 6-CH of Ph,

1H), 8.04 (dt, JHH = 1.40, 8.06 Hz, 5-CH of Ph, 1H), 7.91 (dt, JHH = 1.55, 7.52 Hz, 4-CH of Ph,

1H), 7.73 (m, 4-CH of Py, 1H). 13C{1H} NMR (DMSO-d6, δ): 149.3 (CPy), 146.0 (CPy) , 140.7

(CPy), 136.6 (NCN), 136.0 (CPh), 134.9 (CPh), 134.4 (CPh), 131.5 (CPh), 127.4 (CPh), 125.7 (CPy),

124.5 (Cimid.), 119.7 (Cimid.), 115.0 (CN), 114.7 (CPy), 108.7 (CPh). IR (KBr, cm-1): 2242 (v(CN)).

MS (ESI, methanol/water; m/z): 247.1 (M+). Anal. Calcd for C15H11F6N4P: C, 45.93; H, 2.83; N,

14.28. Found: C, 46.03; H, 3.05; N, 14.51.

2.5.6. Synthesis of 1-(2-Cyanophenyl)-3-(1-phenylethyl)imidazolium Tetrafluoroborate (1e).

A Schlenk flask was charged with (2-cyanophenyl)imidazole (300 mg, 1.8 mmol) and excess (1-

bromoethyl)benzene (1.77g, 8.9 mmol) in dry acetonitrile (10 mL). The reaction mixture was

refluxed for 3 d. The solvent was then removed, and the residue was rinsed with diethyl ether (10

44mL) and dried in vacuo. This residue was extracted further with water (8 mL) and filtered to

remove unreacted (2-cyanophenyl)imidazole. The clear aqueous solution was added to a

saturated aqueous solution (10 mL) of ammonium tetrafluoroborate (223 mg, 2.0 mmol). The

white precipitate was then filtered, rinsed with cold water, and dried in vacuo to give the

analytically pure product. Yield: 119 mg, 19%. 1H NMR (DMSO-d6, δ): 10.01 (s, 2-CH of imid.,

1H), 8.33 (t, JHH = 1.71 Hz, 5-CH of imid., 1H), 8.22 (dd, JHH = 1.17, 7.76 Hz, 3-CH of Ph, 1H),

8.16 (t, JHH = 1.71 Hz, 4-CH of imid., 1H), 8.06 (dd, JHH = 1.08, 7.89 Hz, 6-CH of Ph, 1H), 8.00

(t, JHH = 7.89, 5-CH of Ph, 1H), 7.87 (dt, JHH = 1.21, 7.76 Hz, 4-CH of Ph, 1H), 7.52 – 7.42 (m,

Ph, 5H), 5.95 (q, JHH = 6.96 Hz, CH, 1H), 1.98 (d, JHH = 6.96 Hz, CH3, 3H). 13C{1H} NMR

(DMSO-d6, δ): 138.9 (NCN), 136.7 (CPhCH), 136.3 (CPh), 134.9 (CPh), 134.3 (CPh), 131.3 (CPh),

129.0 (CPhCH), 128.8 (CPh), 127.4 (CPhCH), 126.6 (CPhCH), 124.0 (Cimid), 122.0 (Cimid), 115.1 (CN),

108.9 (CPh), 59.5 (CH), 20.5 (CH3). MS (ESI, methanol/water; m/z): 274.1 (M+). Anal. Calcd for

C18H16F4 BN3: C, 59.86; H, 4.47; N, 11.64. Found: C, 59.77; H, 4.69; N, 11.99.

2.5.7. Synthesis of 1-(2-(Inden-3-yl)ethyl)-3-(2-cyanophenyl)imidazolium Tetrafluoro-

borate (1f). A Schlenk flask was charged with (2-cyanophenyl)imidazole (500 mg, 2.96 mmol)

and 3-(2-bromoethyl)indene (659 mg, 2.96 mmol) in dry acetonitrile (12 mL). The reaction

mixture was refluxed for 4.5 d. After the reaction mixture was cooled to ambient temperature,

the beige solid that was precipitated from the pale-purple solution was filtered and rinsed with

diethyl ether (10 mL). The crude bromide salt of the imidazolium was dissolved in water (5 mL),

and was added to a saturated aqueous solution (10 mL) of ammonium tetrafluoroborate (464 mg,

4.43 mmol). The pale-brown precipitate was then filtered, rinsed with cold water, and dried in

vacuo to give the analytically pure product. Yield: 562 mg, 48%. 1H NMR (DMSO-d6, δ): 9.78

(s, 2-CH of imid., 1H), 8.30 (t, JHH = 1.60 Hz, 4-CH of imid., 1H), 8.21 (dd, JHH = 1.23, 7.75 Hz,

3-CH of Ph, 1H), 8.15 (t, JHH = 1.60 Hz, 5-CH of imid., 1H), 8.03 (dt, JHH = 1.20, 7.90 Hz, 5-CH

of Ph, 1H), 7.85 (m, 4-CH and 6-CH of Ph, 2H), 7.50 (d, JHH = 7.50 Hz, 5-CH of Ar-Ind, 1H),

7.49 (d, JHH = 7.50 Hz, 8-CH of Ar-Ind, 1H), 7.33 (t, JHH = 7.48 Hz, 6-CH of Ar-Ind, 1H), 7.23

(t, JHH = 7.48 Hz, 7-CH of Ar-Ind, 1H), 6.37 (s, CH of Ind, 1H), 4.66 (t, JHH = 7.13 Hz, CH2,

2H), 3.37 (s, CH2 of Ind, 2H), 3.24 (t, JHH = 6.83 Hz, CH2, 2H). 13C{1H} NMR (DMSO-d6, δ):

144.1 (CAr-Ind), 144.0 (CAr-Ind), 138.8 (NCN), 137.6 (CInd), 136.3 (CPh), 135.1 (CPh), 134.5 (CPh),

131.4 (CPh), 130.9 (CInd), 127.4 (CPh), 126.1 (CAr-Ind), 125.0 (CAr-Ind), 123.9 (Cimid), 123.7(CAr-Ind),

123.3 (Cimid), 118.9 (CAr-Ind), 115.1 (CN), 108.8 (CPh), 48.4 (CH2), 37.7 (CH2 of Ind), 27.6 (CH2).

45MS (ESI, methanol/water; m/z): 312.1 (M+). Anal. Calcd for C21H18F4 BN3: C, 63.18; H, 4.54; N,

10.53. Found: C, 63.07; H, 4.75; N, 10.50.

2.5.8. Synthesis of Bis[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene]silver(I)

Tetrafluoroborate ([Ag(C–CN)2]BF4, 2a) . A Schlenk flask was charged with 1a (542 mg, 2

mmol) and silver(I) oxide (695 mg, 3 mmol) in dry acetonitrile (15 mL). The reaction mixture

was refluxed over 3 Å molecular sieves under argon overnight. It was then filtered through a pad

of Celite to give a gold-yellow solution. The volume of solvent was reduced to 3 mL ca., and

diethyl ether (10 mL) was added, which caused fine tan crystals to precipitate from the reaction

mixture. The crystals were then collected on a glass frit and dried in vacuo. Yield: 456 mg, 81%.

Suitable crystals for an X-ray diffraction study were obtained by slow diffusion of diethyl ether

into a saturated solution of 2a in acetonitrile. 1H NMR (CD3CN, δ): 7.88 (dd, JHH = 1.63, 7.68

Hz, 3-CH of Ph, 1H), 7.77 (dt, JHH = 1.63, 7.84 Hz, 5-CH of Ph, 1H), 7.68 (dt, JHH = 1.26, 7.68

Hz, 4-CH of Ph, 1H), 7.55 (dd, JHH = 1.26, 7.84 Hz, 6-CH of Ph, 1H), 7.47 (d, JHH = 1.86 Hz, 5-

CH of imid., 1H), 7.39 (dt, JHH = 1.86 Hz, 4-CH of imid., 1H), 3.85 (s, CH3, 3H). 19F NMR

(CD3CN, δ): -152.2 (s), -152.3 (s). 13C{1H} NMR (CD3CN, δ): 182.6 (Ag–C), 142.1 (CPh) ,

135.0 (CPh), 134.6 (CPh), 130.6 (CPh), 128.5 (CPh), 124.1 (Cimid.), 123.5 (Cimid.), 116.1 (CN), 110.7

(CPh), 39.0 (CH3). IR (KBr, cm-1): 2242, 2227 (v(CN)). Anal. Calcd for C22H18AgBF4N6: C,

47.09; H, 3.23; N, 14.98. Found: C, 46.95; H, 3.39; N, 14.75.

2.5.9. Observation of Silver(I) Complex of (3-(Cyanomethyl)-1-(2-cyanophenyl)-imidazol-2-

ylidene (2b). A Schlenk flask was charged with 1b (354 mg, 1 mmol) and silver(I) oxide (348

mg, 1.5 mmol) in dry acetonitrile (10 mL). The reaction mixture was refluxed over 3Å molecular

sieves under argon overnight. It was then filtered through a pad of Celite to give a gold-yellow

solution. The volume of solvent was removed, and 3 mL of acetonitrile-d3 was added to prepare

samples for NMR analysis. The compound was too unstable to be isolated in its solid state, and

prone to decomposition under light in both solution and solid state. 1H NMR (CD3CN, δ): 7.88

(dd, JHH = 1.57, 7.70 Hz, 3-CH of Ph, 1H), 7.77 (dt, JHH = 1.57, 7.76 Hz, 5-CH of Ph, 1H), 7.70

(dt, JHH = 0.96, 7.70 Hz, 4-CH of Ph, 1H), 7.56 (m, CH of imid., 2H), 7.55 (dd, JHH = 0.96, 7.76

Hz, 6-CH of Ph., 1H), 5.23 (s, CH2, 2H). 19F NMR (CD3CN, δ): -73.3 (d, JPF =707 Hz). 13C{1H}

NMR (CD3CN, δ): 184.4 (Ag–C), 142.0 (CPh) , 135.6 (CPh), 135.1 (CPh), 131.5 (CPh), 128.8

(CPh), 125.0 (Cimid.), 123.8 (Cimid.), 116.4 (PhCN), 116.1 (CH2CN), 110.9 (CPh), 40.4 (CH2).

462.5.10. Observation of Silver(I) Complex of (3-(Carbomoylmethyl)-1-(2-

cyanophenyl)imidazol-2-ylidene (2e). The amide complex of 2b was generated in situ in small

quantities during the preparation of 2b, and was observed by NMR as with 2b. 1H NMR

(CD3CN, δ): 7.86 (m, 3-CH of Ph, 1H), 7.76 (m, 5-CH of Ph, 1H), 7.70 (m, 4-CH of Ph, 1H),

7.55 (m, 6-CH of Ph, 1H), 7.48 (d, JHH = 1.86 Hz, 5-CH of imid., 1H), 7.48 (d, JHH = 1.86 Hz, 4-

CH of imid., 1H), 6.49 (s, br, NH2, 1H), 6.12 (s, br, NH2, 1H), 4.89 (s, CH2, 2H). 19F NMR

(CD3CN, δ): -73.3 (d, JPF = 707 Hz). 13C{1H} NMR (CD3CN, δ): 183.9 (Ag–C), 169.4 (CONH2),

142.3 (CPh) , 135.6 (CPh), 135.1 (CPh), 131.2 (CPh), 128.7 (CPh), 124.6 (Cimid.), 123.9 (Cimid.),

116.6 (PhCN), 110.8 (CPh), 54.2 (CH2).

2.5.11. Synthesis of Bis{[1-(2-cyanophenyl)-3-(2-pyridinylmethyl)imidazol-2-

ylidene]silver(I)} Hexafluorophosphate (2c). A Schlenk flask was charged with 1c (203 mg,

0.5 mmol) and silver(I) oxide (174 mg, 0.75 mmol) in dry acetonitrile (10 mL). The reaction

mixture was refluxed over 3 Å molecular sieves under argon overnight. It was then filtered

through a pad of Celite to give a gold-yellow solution. The volume of solvent was reduced to 1

mL ca., and diethyl ether (8 mL) was added for which tan solids were precipitated from the

reaction mixture. The precipitate was filtered and dried under vacuo to give a tan powder. Yield:

174 mg, 68%. 1H NMR (CD3CN, δ): 8.44 (m, 3-CH of Py, 1H), 7.79 (dd, JHH = 1.16, 7.76 Hz, 3-

CH of Ph, 1H), 7.75 (m, 5-CH of Py, 1H), 7.69 (dt, JHH = 1.16, 8.07 Hz, 5-CH of Ph, 1H), 7.61

(dt, JHH = 1.23, 7.76 Hz, 4-CH of Ph, 1H), 7.52 (dd, JHH = 1.23, 8.07 Hz, 6-CH Ph, 1H), 7.49 (d,

JHH = 1.86 Hz, 4-CH of imid., 1H), 7.48 (d, JHH = 1.86 Hz, 5-CH of imid., 1H), 7.31 (m, 4-CH of

Py, 1H), 7.27 (m, 6-CH of Py, 1H), 5.41 (s, CH2, 2H). 19F NMR (CD3CN, δ): -73.3 (d, JPF = 707

Hz). 13C{1H} NMR (CD3CN, δ): 183.5 (Ag–C), 156.1 (CPy), 151.0 (CPy), 142.5 (CPh), 138.8

(CPy), 135.5 (CPh), 135.1 (CPh), 131.1 (CPh), 128.9 (CPh), 124.7 (CPy), 124.4 (Cimid.), 124.1 (Cimid.),

123.6 (CPy), 116.6 (CN), 111.1 (CPh), 57.8 (CH2). IR (KBr, cm-1): 2236 (v(CN)). Anal. Calcd for

C32H24Ag2F12N8P2: C, 37.45; H, 2.36; N, 10.91. Found: C, 38.04; H, 2.83; N, 10.42.

2.5.12. Synthesis of Bis{[1-(2-cyanophenyl)-3-(2-pyridinyl)imidazol-2-ylidene]silver(I)}

Hexafluorophosphate (2d). A Schlenk flask was charged with 1d (189 mg, 0.48 mmol) and

silver(I) oxide (168 mg, 0.72 mmol) in dry acetonitrile (10 mL). The reaction mixture was

refluxed over 3 Å molecular sieves under argon for overnight. It was then filtered through a pad

of Celite to give a gold-yellow solution. The volume of solvent was reduced to ca. 1 mL, and

diethyl ether (8 mL) was added was added for which beige solids were precipitated from the

reaction mixture. The precipitate was filtered and dried under vacuo to give a beige powder.

47Yield: 150 mg, 63%. 1H NMR (CD3CN, δ): 8.19 (m, 3-CH of Py, 1H), 8.01 (d, JHH = 1.44 Hz, 4-

CH of imid., 1H), 7.88 (m, 5-CH of Py, 1H), 7.86 (d, JHH = 7.40 Hz, 3-CH of Ph, 1H), 7.80 (m,

6-CH of Py, 1H), 7.72 (t, JHH = 7.79 Hz, 5-CH of Ph, 1H), 7.68 (d, JHH = 1.44 Hz, 5-CH of imid.,

1H), 7.67 (t, JHH = 7.40 Hz, 4-CH of Ph, 1H), 7.62 (d, JHH = 7.79 Hz, 6-CH of Ph, 1H), 7.41 (m,

4-CH of Py, 1H). 19F NMR (CD3CN, δ): -73.3 (d, JPF = 707 Hz). 13C{1H} NMR (CD3CN, δ):

183.8 (Ag–C), 151.2 (CPy), 149.9 (CPy), 142.7 (CPh), 140.9 (CPy), 135.5 (CPh), 135.1 (CPh), 131.4

(CPh), 128.9 (CPh), 125.5 (Cimid.), 125.2 (CPy), 121.6 (Cimid.), 116.5 (CPy.), 116.4 (CN), 111.1

(CPh). IR (KBr, cm-1): 2232 (v(CN)). Anal. Calcd for C30H20Ag2F12N8P2: C, 36.10; H, 2.02; N,

11.23. Found: C, 37.17; H, 2.26; N, 11.30.

2.5.13. Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-(η4-1,5-

cycloctadiene)rhodium(I)] Tetrafluoroborate ([Rh(C–CN)(cod)]2(BF4)2, 3). A solution of 2a

(56 mg, 0.1 mmol) and silver tetrafluoroborate (10 mg, 0.05 mmol) in acetonitrile (3 mL) was

added to a solution of [RhCl(cod)2]2 (57 mg, 0.115 mmol) in acetonitrile (2 mL). A pale-brown

precipitate was formed instantaneously. The reaction mixture continued to be stirred for 2 h. It

was then filtered through a pad of Celite to give a bright-yellow solution. The solvent was then

removed in vacuo, and the residue was dissolved in dichloromethane (1 mL). Addition of diethyl

ether (8 mL) caused precipitation of a bright-yellow precipitate. The precipitate was then filtered,

rinsed with diethyl ether (2 mL), and dried in vacuo. Yield: 75 mg, 71%. Suitable crystals for an

X-ray diffraction study were obtained by slow diffusion of diethyl ether into a saturated solution

of 3 in dichloromethane. 1H NMR (CD2Cl2, δ): 8.21 (dd, JHH = 1.40, 7.80 Hz, 3-CH of Ph, 1H),

8.00 (dt, JHH = 1.40, 7.97 Hz, 5-CH of Ph, 1H), 7.90 (dt, JHH = 1.13, 7.80 Hz, 4-CH of Ph, 1H),

7.61 (d, JHH = 2.00 Hz, 5-CH of imid., 1H), 7.55 (dd, JHH = 1.13, 7.97 Hz, 6-CH of Ph, 1H), 7.41

(d, JHH = 2.00 Hz, 4-CH of imid., 1H), 5.16 (m, olefinic-CH of cod, 1H), 4.76 (m, olefinic-CH of

cod, 1H), 4.07 (m, olefinic-CH of cod, 1H), 3.90 (s, CH3, 3H), 2.88 (m, olefinic-CH of cod, 1H),

2.51 (m, CH2 of cod, 1H), 2.24 (m, CH2 of cod, 1H), 2.18 (m, CH2 of cod, 1H), 2.04 (m, CH2 of

cod, 1H), 1.94 (m, CH2 of cod, 1H), 1.88 (m, CH2 of cod, 1H), 1.65 (m, CH2 of cod, 1H), 1.40

(m, CH2 of cod, 1H). 19F NMR (CD2Cl2, δ): -152.3 (s), -152.4 (s). 13C{1H} NMR (CD2Cl2, δ):

178.4 (Rh–C, 1JRh,C = 50.47 Hz), 142.56 (CPh), 136.7 (CPh) , 136.3 (CPh), 131.3 (CPh), 128.6

(CPh), 125.9 (Cimid.), 123.9 (Cimid.), 110.5 (CPh), 108.0 (CN, 2JRh,C = 7.60 Hz), 100.1 (olefinic-C of

cod, 1JRh,C = 7.20 Hz), 99.2 (olefinic-C of cod, 1JRh,C = 6.71 Hz), 83.3 (olefinic-C of cod, 1JRh,C =

13.30 Hz), 79.1 (olefinic-C of cod, 1JRh,C = 12.69 Hz), 38.3 (CH3), 34.2 (CH2 of cod), 30.4 (CH2

of cod), 29.9 (CH2 of cod), 27.8 (CH2 of cod). IR (KBr, cm-1): 2183 (v(CN)). MS (ESI,

48methanol/water; m/z): 394.1 ([0.5 M]+). Several attempts at elemental analyses failed to give an

acceptable carbon content, while hydrogen and nitrogen content are in the acceptable range.

Typical results: Anal. Calcd for C38H42B2F8N6Rh2: C, 47.43; H, 4.40; N, 8.73. Found: C, 45.49;

H, 4.39; N, 8.51.

2.5.14. Synthesis of Bis[chloro-(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)-(η6-p-

cymene)ruthenium(II)] Tetrafluoroborate ([Ru(p-cymene)(C–CN)Cl]2(BF4)2, 4). A solution

of 2a (50 mg, 0.089 mmol) and silver tetrafluoroborate (18 mg, 0.092 mmol) in acetonitrile (4

mL) was added to a solution of [Ru(p-cymene)Cl2]2 (55 mg, 0.090 mmol) in acetonitrile (6 mL).

A pale-brown precipitate was formed instantaneously. The reaction mixture continued to be

stirred for 2 h. It was then filtered through a pad of Celite to give a red-orange solution. The

solvent was then removed in vacuo, and the residue was dissolved in methanol (3 mL). A yellow

precipitate was formed gradually from the homogeneous solution. It was then filtered, rinsed

with diethyl ether (4 mL), and dried in vacuo. Yield: 152 mg, 79%. Suitable crystals for an X-ray

diffraction study were obtained by slow diffusion of diethyl ether into a saturated solution of 4 in

nitroethane. 1H NMR (CD3NO2, δ): 7.99 (m, 4-CH and 6-CH of Ph, 2H), 7.73 (t, JHH = 7.73 Hz,

5-CH of Ph, 1H), 7.66 (d, JHH = 7.46 Hz, 3-CH of Ph, 1H), 7.34 (d, JHH = 2.00 Hz, 4-CH of

imid., 1H), 7.16 (d, JHH = 2.00 Hz, 5-CH of imid., 1H), 6.01 (d, JHH = 5.87 Hz, 2-Ar-CH of p-

cymene, 1H), 5.45 (m, 3-Ar-CH and 6-Ar-CH of p-cymene, 2H), 5.29 (d, JHH = 6.14 Hz, 5-Ar-

CH of p-cymene, 1H), 4.01 (s, CH3, 3H), 2.71 (sept, JHH = 6.91 Hz, CH of (CH3)2CH of p-

cymene, 1H), 2,01 (s, CH3 of p-cymene, 3H), 1.26 (d, JHH = 6.91 Hz, CH3 of (CH3)2CH of p-

cymene, 1H), 1.21 (d, JHH = 6.91 Hz, CH3 of (CH3)2CH of p-cymene, 1H).19F NMR (CD3NO2,

δ): -153.0 (s), -153.1 (s). 13C{1H} NMR (CD3NO2, δ): 170.4 (Ru–C), 144.7 (CPh), 135.8 (CPh) ,

134.0 (CPh), 131.3 (CPh), 130.0 (CPh), 127.4 (Cimid.), 127.1 (Cimid.), 124.8 (CPh), 116.6 (CN), 113.7

(CAr-p-cymene), 105.4 (CAr-p-cymene), 95.2 (CAr-p-cymene), 90.1 (CAr-p-cymene), 84.5 (CAr-p-cymene), 83.6

(CAr-p-cymene), 40.5(CH3), 32.6 (CH of (CH3)2CH of p-cymene), 23.5 (CH3 of p-cymene), 21.9,

(CH3 of (CH3)2CH of p-cymene), 19.0 (CH3 of (CH3)2CH of p-cymene). MS (ESI, methanol/

water; m/z): 454.1 (0.5 M+), 418.1 ([0.5 (M – Cl)]+). Anal. Calcd for C42H46B2Cl2F8N6Ru2: C,

46.64; H, 4.29; N, 7.77. Found: C, 46.26; H, 3.96; N, 7.86

49Chapter 3: Palladium(II) and Platinum(II) Complexes Featuring a

Nitrile-Functionalized N-Heterocyclic Carbene Ligand

3.1 Abstract

The transmetalation reaction of 2 equiv of trans-PdCl2(CH3CN)2 or Pd(cod)Cl2 with a nitrile-

functionalized N-heterocyclic carbene (C–CN) complex of silver(I), bis[1-(2-cyanophenyl)-3-

methylimidazol-2-ylidene]silver(I) tetrafluoroborate ([Ag(C–CN)2]BF4 2a), and 1 equiv of

AgBF4 afforded a bimetallic complex formulated as [(C–CN)2Pd(μ-Cl)2Pd(CH3CN)2](BF4)2 (5a).

The interesting trimetallic complex 5b was obtained during an attempt to crystallize 5a from wet

diethyl ether and acetonitrile. The solid-state structure of 5b reveals the presence of a novel C–

N–N–C donor ligand providing two bridging imido nitrogens to adjacent palladium(II) centers in

the trimetallic complex [{Pd(CH3CN)2}3(C–N–N–C)](BF4)4 (5b). The C–N–N–C ligand, which

has a central –N=C–O–C=N– linkage, was formed from the hydrolysis and condensation of the

nitrile groups of two carbene ligands. Palladium(II) and platinum(II) complexes bearing

chelating olefin and N-heterocyclic carbene (NHC) ligands were synthesized by transmetalation

reactions of N-heterocyclic carbene complexes of silver(I), complex 2a and bis[1,3-bis(2,4,6-

trimethyl-phenyl)imidazol-2-ylidene]silver(I) tetrafluoroborate ([Ag(IMes)2]BF4, 10), with

[Pd(η1:η2-coe-OMe)(μ-Cl)]2 and Pt(cod)Cl2 (coe-OMe = 2-methoxycyclooct-5-enyl, cod = 1,5-

cyclooctadiene) or by addition of a methoxide anion to the coordinated diolefin ligand of the

platinum(II) complex, chloro[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene](η4-1,5-

cyclooctadiene)-platinum(II) tetrafluoroborate (7). The complexes bearing the C–CN and 2-

methoxycyclooct-5-enyl ligands ([M(C–CN)(η1:η2-coe-OMe)]+: 6, M = Pd; 9, M = Pt) exists in

both monomeric and dimeric forms depending on the choice of recrystallization solvents. All of

these complexes were isolated and studied by NMR and infrared spectroscopy. Different ratios

of rotamers were observed for the complexes bearing a 2-methoxycyclooct-5-enyl ligand owing

to its orientation relative to the carbene ligand. Rotamers are believed to form because of steric

restrictions to rotation about the M–Ccarbene bond (M = Pd, Pt).

*Reproduced in part with permission from O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2010, 29, 570-581. Copyright 2010 American Chemical Society.

503.2 Introduction

Donor functionalized N-heterocyclic carbenes (NHC) have exceptional utility in the synthesis

of novel and highly active homogeneous catalysts in the fields of organometallic and synthetic

organic chemistry.1 The versatility in the mode of coordination of these ligands and, more

importantly, their ability to promote oxidative addition, reductive elimination, and

dehydrohalogenation reactions in catalytic reactions have been extensively reviewed in the

literature in recent years.2

Our group has been interested in the development of catalysts for the hydrogenation of polar

bonds, including those of ketones, imines, and nitriles. High activities were reported for

ruthenium(II)3 and iron(II)4 based catalysts bearing phosphino-amino ligands. We have reported

the syntheses of coordinatively unsaturated hydridoruthenium(II) complexes bearing N-

heterocyclic carbene ligands,5 and nitrile-functionalized N-heterocyclic carbene ligands and their

metal complexes of silver(I), rhodium(I) and ruthenium(II) (Chapter 2 and Figure 3.1).6 The

nitrile functionality on these carbene ligands can bridge to metal centers, and can be hydrolyzed

with the assistance of silver ions, giving primary amido-functionalized N-heterocyclic carbene

ligands.6

In our continuing investigation of the coordinating ability and reactivity of these nitrile-

functionalized N-heterocyclic carbene ligands, and N-heterocyclic carbene ligands in general and

their late transition metal complexes, we report in this chapter the synthesis and studies of

palladium(II) and platinum(II) complexes bearing N-heterocyclic carbene and olefin ligands,

which predominantly have the general structures shown in Figure 3.1. Of particular interest is the

reactivity of the coordinated olefin and nitriles in these metal complexes.7

1. (a) Kuhl, O., Chem. Soc. Rev. 2007, 36, 592-607; (b) Liddle, S. T.; Edworthy, I. S.; Arnold, P. L., Chem. Soc. Rev. 2007, 36, 1732-1744; (c) Hahn, F. E.; Jahnke, M. C., Angew. Chem. Int. Ed. 2008, 47, 3122-3172; (d) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676.2. (a) Crudden, C. M.; Allen, D. P., Coord. Chem. Rev. 2004, 248, 2247-2273; (b) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (c) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (d) Poyatos, M.; Mata, J. A.; Peris, E., Chem. Rev. 2009, 109, 3677-3707; (e) Corberan, R.; Mas-Marza, E.; Peris, E., Eur. J. Inorg. Chem. 2009, 1700-1716.3. (a) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529; (b) Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579; (c) Guo, R.; Morris, R. H.; Song, D., J. Am. Chem. Soc. 2005, 127, 516-517.4. Morris, R. H., Chem. Soc. Rev. 2009, 38, 2282-2291 and references therein.5. Abdur-Rashid, K.; Fedorkiw, T.; Lough, A. J.; Morris, R. H., Organometallics 2004, 23, 86-94.6. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 853-862.7. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2010, 29, 570-581.

51

Figure 3.1. Nitrile-functionalized N-heterocyclic carbene complexes of Ag(I) and Rh(I) and the

general structures of the complexes reported in this chapter (M = Pd(II), Pt(II); D = olefin or

alkyl ligand; L = nitrile donor or a chloro group).


3.3.1 Transmetalation of a Nitrile-Functionalized N-heterocyclic Carbene Ligand from

Silver(I) to Palladium(II). The transmetalation reaction8 of [Ag(C–CN)2]BF4 (2a) with 2 equiv

of trans-PdCl2(CH3CN)2 and 1 equiv of AgBF4 afforded the bimetallic complex 5a as a yellow

powder in 62% yield. Alternatively, the complex could also be prepared using Pd(cod)Cl2 in

higher yields (79%) (Scheme 3.1). The reaction did not proceed cleanly when only 1 equiv of the

palladium(II) precursor was used. Although crystals suitable for X-ray diffraction were not

obtained successfully, the structure of 5a can be elucidated by spectroscopic data and elemental

analysis. The 13C{1H} NMR spectrum in acetonitrile-d3 solution shows a singlet at 141.4 ppm,

which was assigned to the carbene carbon (Pd–Ccarbene) according to a 1H-13C HMBC

experiment. Although it is shifted upfield compared to most Pd(NHC)2X2 (X = halide) systems,9

it is in the expected range when compared to cationic cis-[Pd(NHC)2(CH3CN)X]+ or cis-

[Pd(NHC)2(CH3CN)2]2+ systems.10 The nitrile stretching frequencies in the infrared spectrum

8. Lin, J. C. Y.; Huang, R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B., Chem. Rev. 2009, 109, 3561-3598.9. (a) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus, G. R. J., Angew. Chem. Int. Ed. 1995, 34, 2371-2374; (b) Ku, R. Z.; Huang, J. C.; Cho, J. Y.; Kiang, F. M.; Reddy, K. R.; Chen, Y. C.; Lee, K. J.; Lee, J. H.; Lee, G. H.; Peng, S. M.; Liu, S. T., Organometallics 1999, 18, 2145-2154; (c) Magill, A. M.; McGuinness, D. S.; Cavell, K. J.; Britovsek, G. J. P.; Gibson, V. C.; White, A. J. P.; Williams, D. J.; White, A. H.; Skelton, B. W., J. Organomet. Chem. 2001, 617-618, 546-560; (d) Grundemann, S.; Albrecht, M.; Kovacevic, A.; Faller, J. W.; Crabtree, R. H., Dalton Trans. 2002, 2163-2167; (e) Fu, C. F.; Lee, C. C.; Liu, Y. H.; Peng, S. M.; Warsink, S.; Elsevier, C. J.; Chen, J. T.; Liu, S. T., Inorg. Chem. 2010, 49, 3011-3018.10. Scherg, T.; Schneider, S. K.; Frey, G. D.; Schwarz, J.; Herdtweck, E.; Herrmann, W. A., Synlett 2006, 2894-2907.11. (a) Andrews, M. A.; Chang, T. C. T.; Cheng, C. W. F.; Emge, T. J.; Kelly, K. P.; Koetzle, T. F., J. Am. Chem. Soc. 1984, 106, 5913-5920; (b) Mitsudo, K.; Kaide, T.; Nakamoto, E.; Yoshida, K.; Tanaka, H., J. Am. Chem. Soc. 2007, 129, 2246-2247.

NN

NCH3

MD

L

M = Pd(II), Pt(II)

This chapter

n+

NN

NCH3

BF4Ag

NN

NCH3

(BF4)2

RhN

NN

RhN

NN

H3C

CH3

+

+

+

2a 3

52suggested the presence of coordinated acetonitrile11 and non-coordinated nitrile groups of

carbene ligands (2329 and 2237 cm-1, respectively). Of note, the nitrile stretching frequency on

the carbene ligand is significantly higher compared to 3 bearing the same ligand with bridging

nitrile groups (2183 cm-1).6 The complex is formulated as [Pd(C–CN)Cl(CH3CN)(BF4)]n

according to elemental analysis. The ion [Pd(C–CN)2Cl]+ is the major species revealed by

electrospray-ionization mass spectrometry (ESI-MS). We therefore propose that the compound

has the structure [(C–CN)2Pd(μ-Cl)2Pd(CH3CN)2](BF4)2, where the chloro ligands bridge

between two palladium(II) centers and the two carbene ligands are coordinated to one metal

center.

Scheme 3.1. Synthesis of Pd(II) and Pt(II) Complexes (5, 6a, and 7) Starting from a Nitrile-

Functionalized N-Heterocyclic Carbene Complex of Ag(I) (2a).

AgBF4

2

2 Pt(cod)Cl2AgBF4

CH2Cl2:CH3CN(5:2), rt

N

NCH3

Pt

Cl

N

BF4

[Pd(η 1:η 2-coe-OMe)(µ -Cl)]2

2

Pd (BF4)2Cl

ClPd

NN

H3C

N

NCH3

NCH3N

NH3C

N

2 trans-PdCl2(CH3CN)2

AgBF4CH3CN, rt

5a

or 2 Pd(cod)Cl2

Pd

H3CO N

N

N

NCH3

CH3

H BF4

4+

PdPd

Pd

ON

N

NN

NN

NN

NNNN

CH3

CH3CH3H3CH3C

H3C

CH3H3C

trace H2OCH3CN/Et2O

5b

(BF4)4

7

CH2Cl2:CH3CN(3:2), rt:

6a

NN

NCH3

BF4Ag

NN

NCH3

2a

+

+

+

+ +

533.3.2 Hydrolysis of Nitrile-Functionalized N-Heterocyclic Carbene Ligands on

Palladium(II) Centers. In an attempt to obtain a crystal structure of 5a using wet diethyl ether

layered on top a saturated solution of the complex in acetonitrile, the C–CN ligands were

hydrolyzed, leading to formation of very small amounts of crystals, which in turn were

characterized by X-ray diffraction as the trimetallic complex 5b (Figure 3.2). Despite the

presence of disordered diethyl ether molecules in the lattice, this contribution to the electron

density was removed from the observed data during refinement and resulted in a significant

increase in the precision of the geometric parameters.7 Complex 5b contains a C–N–N–C donor

ligand providing two bridging imido nitrogens in the trimetallic complex [{Pd(CH3CN)2}3(C–N–

N–C)](BF4)4; the C–N–N–C ligand, which has a central –N=C–O–C=N– linkage, is formed from

the partial hydrolysis of the nitrile moiety to a primary amido group6 followed by a condensation

reaction with elimination of water. Each square-planar palladium(II) center has two cis

acetonitrile ligands. The coordination geometry around the central palladium(II) center

comprises of a six-membered ring with a –Pd–N=C–O–C=N– linkage and resembles that of a β-

diketiminato complex.12 To our knowledge, there are only few examples of organic compounds

with the general formula R–N=CR'–O–R'C=N–R reported in the literature (R = H, alkyl).13 The

outer palladium(II) cations are coordinated to the bridging imido nitrogen and the carbene carbon

of the N-heterocyclic carbene, thus forming a seven-membered ring (Figure 3.2). Bridging

groups with this type of nitrogen are rare. Shriver and co-workers have reported the structural

characterization of metal carbonyl cluster complexes with an acetamido ligand bridging between

three heterometal centers (Ru, Mn, Re) via nitrogen and coordination to ruthenium via its

oxygen.14 Mehrotra and Verkade have reported structures with trialkylstannates bridged by

acetamido ligands.15 More recently, Besenyei have reported the synthesis of some bridging

phenylacetamido complexes of palladium(II) from reactions of benzoyl azides with

[PdCl(dppm)]2 (dppm = 1,1-bis(diphenylphosphino)methane).16

12. Hadzovic, A.; Song, D., Organometallics 2008, 27, 1290-1298.13. (a) Gramstad, T.; Husebye, S.; Saebo, J., Tet. Lett. 1983, 24, 3919-3920; (b) Hitzler, M. G.; Lutz, M.; Shrestha-Dawadi, P. B.; Jochims, J. C., Liebigs Ann. 1996, 247-257.14. (a) Voss, E. J.; Sabat, M.; Shriver, D. F., Inorg. Chem. 1991, 30, 2705-2707; (b) Voss, E. J.; Sabat, M.; Shriver, D. F., Inorg. Chim. Acta 1995, 240, 49-61.15. (a) Sharma, K. K.; Mehrotra, S. K.; Mehrotra, R. C., J. Organomet. Chem. 1977, 142, 165-169; (b) Geetha, S.; Ye, M. C.; Verkade, J. G., Inorg. Chem. 1995, 34, 6158-6162.16. Besenyei, G.; Parkanyi, L.; Szalontai, G.; Holly, S.; Papai, I.; Keresztury, G.; Nagy, A., Dalton Trans. 2004, 2041-2050.

54

Figure 3.2. ORTEP diagram of 5b⋅1.5 CH3CN depicted with thermal ellipsoids at the 30%

probability level. The counteranions, hydrogens, and solvent molecules have been omitted for

clarity. Selected bond distances (Å) and bond angles (deg): Pd(1)-C(1), 1.969(6); Pd(3)-C(20),

1.957(6); Pd(1)-N(3), 2.015(5); Pd(3)-N(4), 2.018(5); Pd(2)-N(3), 1.976(5); Pd(2)-N(4),

1.972(5); Pd(1)-N(8), 2.094(6); Pd(1)-N(7), 2.020(5); C(10)-N(3), 1.272(8); C(11)-N(4),

1.265(8); C(10)-O(1), 1.361(7); C(11)-O(1), 1.382(7); N(3)-Pd(2)-N(4), 91.9(2); C(1)-Pd(1)-

N(3), 85.4(2); C(10)-O(1)-C(11), 126.7(5); C(10)-N(3)-Pd(2), 125.3(4).

The solid state structure of 5b shows square-planar geometries about the metal centers, and

the phenyl rings are twisted with respect to the imidazolylidene rings at dihedral angles 41.00

and 41.13° to facilitate chelation. The C(10)-N(3) and C(11)-N(4) bond distances (1.272(8) and

1.265(8) Å) reveal a double bond character between carbon and nitrogen atoms, forming an

imido linkage (cf. CPh–C(sp2)=N–Cavg = 1.279 Å; C(sp3)–Navg = 1.46 - 1.48 Å).17 On the other

hand, the C–O distances (1.361(7) and 1.382(7) Å) are shorter than a C(sp3)–O bond (C(sp3)–

Oavg = 1.42 - 1.45 Å for ethers) and slightly longer than the C(sp2)–O bonds of organic amides

(C(sp2)–Oavg = 1.23 Å).17 These all suggest delocalization of electrons through the π-orbitals of

the –N=C–O–C=N– bonds. In addition, the Pd(2)-N(3) and Pd(2)-N(4) bond distances (1.976(5)

and 1.972(5) Å) are significantly shorter than a Pd–RN=CR2 motif (Pd–Navg = 2.037Å),18

17. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A. G.; Taylor, R., J. Chem. Soc., Perkin Trans. 2 1987, S1-S19.18. Orpen, A. G.; Brammer, L.; Allen, F. H.; Kennard, O.; Watson, D. G.; Taylor, R., Dalton Trans. 1989, S1-S83.

55reflecting the presence of highly charged bridging imido nitrogen atoms. The Pd–Ccarbene bond

distances lie within the typical range for Pd(NHC) complexes.9a, 9d, 9e, 10, 19 The carbene ligand has

a stronger trans influence than the bridging-imido groups, as reflected by the Pd–Nacetonitrile bond

lengths (Pd(1)-N(8)trans to C = 2.094(6), Pd(1)-N(7)trans to N = 2.020(5) Å).

The mechanism in the formation of complex 5b from a solution of 5a is not well understood.

It is believed that the carbene ligands on the palladium(II) center of 5a serve as a base in the

deprotonation of water in the cooperative hydrolysis of the nitrile moieties. Cooperative

hydrolysis of nitrile was observed in cis-dialkylcyanamide complexes of platinum(IV)

(cis-PtCl4(NCNR2)2, R = CH3, C2H5, C5H10) to a diimino complex of platinum(IV)

(cis-PtCl4(NC–R2N–μ-O–NR2–CN)) under base-free conditions.20 We attempted to synthesize 5b

independently to obtain spectroscopic information, by stoichiometric reaction of 3 equiv of

trans-PdCl2(CH3CN)2, 2 equiv of 2a, 4 equiv of silver tetrafluoroborate and water in acetonitrile.

This gave a mixture of a palladium complex and free imidazolium salt (1a, see chapter 2). The 13C{1H} NMR spectrum of this mixture in acetonitrile-d3 revealed a peak at 141.4 ppm of the

carbene carbon (Pd–Ccarbene), and a peak at 169.1 ppm which is suggestive of an amido-carbon.

The nitrile carbons on the ligands were not observed. No primary or secondary amido groups

were observed in the 1H NMR spectrum. However, these spectroscopic data are insufficient to

identify the presence of 5b in this stoichiometric reaction.

3.3.3 Palladium(II) Complex Bearing Nitrile-Functionalized N-Heterocyclic Carbene

(C–CN) and Methoxycyclooctenyl Ligands. In order to obtain more well-defined palladium(II)

complexes with the C–CN ligand, the reactions of other palladium(II) precursors with the

silver(I) complex [Ag(C–CN)2]BF4 (2a) were explored. Attempts using PdCl2(en),21

[Pd(CH3CN)4](BF4)2,22 and [Pd(cod)(μ-Cl)]2(BF4)223 (en = ethylenediamine, cod = 1,5-

cyclooctadiene) as starting materials failed. The palladium(II) precursor [Pd(η1:η2-coe-OMe)(μ-

Cl)]2 (coe-OMe = 2-methoxycyclooct-5-enyl)24 can be conveniently prepared as the exo isomer

19. (a) Meyer, A.; Taige, M. A.; Strassner, T., J. Organomet. Chem. 2009, 694, 1861-1868; (b) Kantchev, E. A. B.; Ying, J. Y., Organometallics 2009, 28, 289-299; (c) Tang, Y. Q.; Lu, J. M.; Wang, X. R.; Shao, L. X., Tetrahedron 2010, 66, 7970-7974; (d) Warsink, S.; Drost, R. M.; Lutz, M.; Spek, A. L.; Elsevier, C. J., Organometallics 2010, 29, 3109-3116; (e) Hashmi, A. S. K.; Lothschutz, C.; Bohling, C.; Rominger, F., Organometallics 2011, 30, 2411-2417.19.20. Bokach, N. A.; Pakhomova, T. B.; Kukushkin, V. Y.; Haukka, M.; Pombeiro, A. J. L., Inorg. Chem. 2003, 42, 7560-7568.21. Hohmann, H.; Vaneldik, R., Inorg. Chim. Acta 1990, 174, 87-92.22. Thomas, R. R.; Sen, A.; Beck, W.; Leidl, R., Inorg. Synth. 1989, 26, 128-134.23. Eaborn, C.; Farrell, N.; Pidcock, A., Dalton Trans. 1976, 289-292.24. Bailey, C. T.; Lisensky, G. C., J. Chem. Educ. 1985, 62, 896-897.

56by the reaction of Pd(cod)Cl2 and sodium methoxide in methanol. When this was reacted with 1

equiv of 2a and AgBF4, a white complex 6a, [Pd(η1:η2-coe-OMe)(C–CN)(CH3CN)]BF4, was

isolated in 67% yield. The product exists as mixture of diastereomers, which includes rotamers A

and B and each of their enantiomers, with chiral centers at the C(1) and C(2) carbons (see Figure

3.3 for the numbering schemes). The rotamers are believed to form via restricted rotation about

the M–Ccarbene bond (M = Pd, Pt; vide infra) owing to the steric crowd of the neighboring 2-

methoxycyclooct-5-enyl ligand. Grubbs and co-workers showed that a ruthenium alkylidene

complex with a saturated N-heterocyclic carbene with o-tolyl groups on the nitrogens has a

restricted rotation around the Ru–Ccarbene bond. The o-tolyl groups have a smaller barrier to

rotation than the Ru–Ccarbene bond but do cause the formation of rotamers about the CPh–Nimid

bonds.25 A second explanation is that there are geometric isomers with the carbene ligand trans to

the chelating olefin and the carbene ligand trans to the σ-alkyl group. These, however, are

unlikely, as the 13C{1H} NMR resonances of these carbons fortuitously have the same chemical

shifts (with a difference less than 10 Hz), whereas a chemical shift difference of up to 150 Hz

was observed if these geometric isomers do exist.26

Figure 3.3. Diastereomers and rotamers (A and B) of Pd(II) (6a) and Pt(II) (9a) complexes

bearing 2-methoxycyclooct-5-enyl and the C–CN ligands.

25. Stewart, I. C.; Benitez, D.; O'Leary, D. J.; Tkatchouk, E.; Day, M. W.; Goddard, W. A.; Grubbs, R. H., J. Am. Chem. Soc. 2009, 131, 1931-1938.26. Cooper, D. G.; Powell, J., Inorg. Chem. 1977, 16, 142-148.

18BF4

6a: M = Pd9a: M = Pt

A-(1S,2S) A-(1R,2R)

B-(1S,2S) B-(1R,2R)

M

H3CON

N

N

NCH3

CH3

6

54

3

2H

7

BF4

NN N

H3C

NN

N

CH3

BF4M

OCH3NN

N

NCH3

CH3

H

18

M

H3CO

N

CH3

6

54

3

2H7

BF4M

OCH3

N

CH3

H

+ +

+ +

57

Figure 3.4. ORTEP diagram of 6a depicted with thermal ellipsoids at the 30% probability level.

The counteranion and hydrogens have been omitted for clarity. Selected bond distances (Å) and

bond angles (deg): Pd(1)-C(1), 2.012(4); Pd(1)-C(19), 2.040(4); Pd(1)-N(4), 2.164(3); Pd(1)-

coe(trans to C)cent, 2.161; C(11)-N(3), 1.148(6); C(18)-O(1), 1.441(5); C(1)-Pd(1)-coe(trans to

C)avg, 161.2; C(19)-Pd(1)-N(4), 177.2(9); C(1)-Pd(1)-C(19), 87.7(1).

Slow diffusion of diethyl ether into a saturated solution of 6a afforded white needles which

were then characterized by X-ray diffraction (Figure 3.4). The square-planar complex

crystallizes in the chiral triclinic space group P-1 with the exo-S,S rotamer A being observed

(Figures 3.3 and 3.4). The carbene ligand is oriented trans to the cyclooctene ligand. The Pd–C

bond distances of the carbene9c-e, 19d, 27 (Pd–Ccarbene) and methoxycyclooctenyl (Pd–C(1))28 ligands

are within expected ranges. On the other hand, the acetonitrile ligand is weakly coordinated,

owing to the strong trans influence of the σ-alkyl group (2.164(3) Å; cf. 2.06 Å in

PdCl2(CH3CN)(μ-dpmp)PdCl229 and 2.01 - 2.09 Å in 5b; dpmp = bis((diphenylphosphino)-

methyl)phenylphosphine). The dihedral angle between the 2-cyanophenyl and the

27. Li, D. C.; Liu, D. J., J. Chem. Crystallogr. 2003, 33, 989-991.28. (a) Hoel, G. R.; Stockland, R. A.; Anderson, G. K.; Ladipo, F. T.; Braddock-Wilking, J.; Rath, N. P.; Mareque-Rivas, J. C., Organometallics 1998, 17, 1155-1165; (b) Macchioni, A.; Bellachioma, G.; Cardaci, G.; Travaglia, M.; Zuccaccia, C.; Milani, B.; Corso, G.; Zangrando, E.; Mestroni, G.; Carfagna, C.; Formica, M., Organometallics 1999, 18, 3061-3069; (c) Binotti, B.; Bellachioma, G.; Cardaci, G.; Macchioni, A.; Zuccaccia, C.; Foresti, E.; Sabatino, P., Organometallics 2002, 21, 346-354; (d) Binotti, B.; Bellachioma, G.; Cardaci, G.; Carfagna, C.; Zuccaccia, C.; Macchioni, A., Chem. Eur. J. 2007, 13, 1570-1582.29. Olmstead, M. M.; Guimerans, R. R.; Farr, J. P.; Balch, A. L., Inorg. Chim. Acta 1983, 75, 199-208.

58imidazolylidene rings of the carbene ligand is 59.38°, large enough to relieve steric repulsion

between the coordinated ligands. The infrared spectrum of 6a displays two nitrile stretches at

2277 cm-1 for the carbene ligand and 2229 cm-1 for the coordinated acetonitrile.

In nitromethane-d3 solution, the carbene atom (Pd–Ccarbene) of the NHC ligand was observed

as a singlet at 174.2 ppm in the 13C{1H} NMR spectrum. All of the proton and carbon resonances

of the methoxycyclooctenyl ligand were assigned by 1H-1H COSY, 1H-13C HSQC, and 1H-13C

HMBC experiments based on the distinctive resonance28 of the C(2) carbon in the 13C{1H} NMR

spectrum. The two enantiomers of a single rotamer are not distinguishable by one-dimensional 1H NMR spectroscopy. However, the rotamers A and B of 6a in nitromethane-d3 solutions are

distinguishable in the 13C{1H} NMR spectrum, where the resonance of each carbon appears in a

1:4 ratio, and in the 1H NMR spectrum, where there are two resonances of the H(1) proton of the

methoxycyclooctenyl ligand. The other peaks of the methoxycyclooctenyl ligand were

overlapping with each other so that the exact ratio could not be determined. As no single crystal

was isolated as the rotamer B, it is therefore expected, on the basis of the NMR data, that there

exists approximately 20 mol% of the isolated product containing the rotamer B. The 1H and 13C{1H} NMR spectra of the platinum(II) analogues also provide evidence for the existence of

these rotamer (vide infra).

Scheme 3.2. Interconversion of 6a to 6b and 9a to 9b in Different Recrystallization Solvents.

When 6a was recrystallized in dichloromethane and diethyl ether mixtures, the acetonitrile

ligand was lost and the corresponding dimer 6b was isolated (Scheme 3.2). The rhodium(I)

complex 3 bearing the same bridging C–CN ligand was isolated as a dimer (See Chapter 2 and

Figure 3.1).6 The identity of 6b was established for its nitromethane-d3 solution by the absence of

the resonance at 2.01 ppm for coordinated acetonitrile ligand in the 1H NMR spectrum. The

nitrile stretch of the acetonitrile ligand was absent in the infrared spectrum. There is a slight

NNH3C

N(BF4)2

M

M

H3CO

OCH3

6b:M = Pd9b:M = Pt

BF4M

H3CO N

N

N

NCH3

CH3

6a: M = Pd9a: M = Pt

H

H

H

NN CH3

N

CH3CN/Et2O

CH2Cl2/Et2O

+

++

59decrease in the stretching frequency of the nitrile moiety of the carbene ligand on going from

complex 6a (2277 cm-1) to 6b (2260 cm-1), signaling the effect of coordination to palladium(II)

center. Complex 6a can be crystallized from a solution of 6b in acetonitrile and diethyl ether,

suggesting the lability of the nitrile groups of both the acetonitrile and carbene ligand. Of note,

the 2-cyanophenyl group of the carbene ligand has to rotate about the C–N bond by 180° to

allow this interconversion of the structures.

It should be noted that solutions of 6a and 6b are extremely sensitive to light and are prone to

β-hydride elimination to release cyclooctadienyl methyl ethers and then reductive elimination of

the palladium hydride to release the imidazolium salt with the formation of black palladium(0)

metal. Reductive elimination of N-heterocyclic carbene ligands can occur when they are not

tethered to the metal by a second donor group from the carbene ligand.1c The organic products

were identified by 1H NMR.30 In addition, complex 6a is also light sensitive in its solid state to

form palladium metal. Pure 6a can be recovered by filtration of the palladium metal from a

solution of the compound exposed to light and then recrystallization in acetonitrile and diethyl

ether solution. Complex 6b in its solid state is less sensitive to light and can be stored without

further decomposition.

In fact, attempts at catalysis using complex 6b (2 mol% of Pd) for the Buchwald-Hartwig

amination reactions31 was not successful, starting from 4-chlorotoluene or 4-bromotoluene,

morpholine and base (K2CO3, Cs2CO3, NaOtBu, KOtBu) in various temperatures (up to 100°C)

and different solvents (dimethoxyethane, dimethylacetamide and toluene). The decomposition of

the complex and the formation of palladium(0) metal were observed in all cases.

3.3.4 Nitrile-Functionalized N-Heterocyclic Carbene Complex of Platinum(II). Initial

attempts using both isomers of PtCl2(CH3CN)232 as starting materials in the transmetalation

reaction with [Ag(C–CN)2]BF4 (2a) and AgBF4 failed. Only starting materials were recovered,

even if the reactions were carried out at elevated temperatures. On the other hand, the reaction of

2a with 2 equiv of Pt(cod)Cl2 and 1 equiv of AgBF4 in acetonitrile and dichloromethane

mixtures afforded complex 7, [Pt(C–CN)(cod)Cl]BF4, as a white solid in 59% yield. The slightly

distorted square-planar complex (Figure 3.5) crystallizes in the monoclinic space group P21/n

30. Anderson, C. B.; Burreson, B. J.; Michalowski, J. T., J. Org. Chem. 1976, 41, 1990-1994.31. (a) Hartwig, J. F., Angew. Chem.-Int. Edit. 1998, 37, 2047-2067; (b) Hartwig, J. F., Acc. Chem. Res. 1998, 31, 852-860; (c) Surry, D. S.; Buchwald, S. L., Chem. Sci. 2011, 2, 27-50.32. Fraccarollo, D.; Bertani, R.; Mozzon, M.; Belluco, U.; Michelin, R. A., Inorg. Chim. Acta 1992, 201, 15-22.

60with four units residing in the unit cell. The cyclooctadiene ligand is coordinated to the metal

center with bond distances from the centroid of each olefin being 2.152 and 2.048 Å. The longer

distance (2.152 Å) corresponds to that for the olefin trans to the carbene ligand, and the shorter

C=C bond distance of this olefin compared to that trans to the chloro is consistent with a higher

trans influence of the carbene ligand (C(16)-C(17)trans to C, 1.372(8) Å; C(12)-C(13)trans to Cl,

1.408(7) Å). The carbene ligand that is bonded to the metal center is oriented with a dihedral

angle between the phenyl and imidazolylidene ring of 51.70°, and the nitrile moiety is directed

away from the metal center. The Pt–Ccarbene bond distance is in the expected range for

platinum(II) compounds bearing NHC ligands.33 A similar cationic platinum(II) complex with a

diolefin and an N-heterocyclic carbene ligand with a cyclometalated phenyl ring of the carbene

ligand, [Pt(dpim)(cod)]ClO4 (dpim = 1,3-diphenyl-2-imidazolidinylidenato-2-C,2'-C), was

reported by Hiraki and co-workers.34

The 13C{1H} NMR spectrum in acetonitrile-d3 solution of 7 shows a singlet for the carbene

carbon (Pt–Ccarbene) at 151.4 ppm; this is shifted upfield compared to the case for most

Pt(NHC)2X2 systems.9b, 19a, 33a, 33c-e, 34-35 Platinum satellites were observed at the four olefinic

carbons bonded to the metal center (1JPt-C = 31.54, 31.92, 75.12, and 80.20 Hz) and for two

olefinic protons (2JPt-H = 30.72 and 32.61 Hz). The resonances with smaller 1JPt-C coupling

constants are assigned to the olefinic C–H trans to the carbene ligand. Similar observations were

reported and discussed by Clark and Manzer,36 Appleton,37 Anderson38 and Klein.39 Attempts to

remove the cyclooctadiene and the chloro ligands by reduction of the olefin and reaction with

silver(I) salts, respectively, were not successful.

33. (a) Bacciu, D.; Cavell, K. J.; Fallis, I. A.; Ooi, L. L., Angew. Chem. Int. Ed. 2005, 44, 5282-5284; (b) Baker, M. V.; Brown, D. H.; Simpson, P. V.; Skelton, B. W.; White, A. H.; Williams, C. C., J. Organomet. Chem. 2006, 691, 5845-5855; (c) Brissy, D.; Skander, M.; Retailleau, P.; Marinetti, A., Organometallics 2007, 26, 5782-5785; (d) Fantasia, S.; Petersen, J. L.; Jacobsen, H.; Cavallo, L.; Nolan, S. P., Organometallics 2007, 26, 5880-5889; (e) Zhang, Y. Z.; Garg, J. A.; Michelin, C.; Fox, T.; Blacque, O.; Venkatesan, K., Inorg. Chem. 2011, 50, 1220-1228.34. Hiraki, K.; Onishi, M.; Ohnuma, K.; Sugino, K., J. Organomet. Chem. 1981, 216, 413-419.35. (a) Riederer, S. K. U.; Bechlars, B.; Herrmann, W. A.; Kuhn, F. E., Eur. J. Inorg. Chem. 2011, 249-254; (b) Taige, M. A.; Ahrens, S.; Strassner, T., J. Organomet. Chem. 2011, 696, 2918-2927.36. Clark, H. C.; Manzer, L. E., J. Organomet. Chem. 1973, 59, 411-428.37. Appleton, T. G.; Clark, H. C.; Manzer, L. E., Coord. Chem. Rev. 1973, 10, 335-422.38. Anderson, G. K.; Clark, H. C.; Davies, J. A., Inorg. Chem. 1981, 20, 1636-1639.39. Klein, A.; Klinkhammer, K. W.; Scheiring, T., J. Organomet. Chem. 1999, 592, 128-135.

61

Figure 3.5. ORTEP diagram of 7 depicted with thermal ellipsoids at the 30% probability level.

The counteranion and hydrogens have been omitted for clarity. Selected bond distances (Å) and

bond angles (deg): Pt(1)-C(1), 2.011(5); Pt(1)-Cl(1), 2.317(6); Pt(1)-cod(trans to C)cent, 2.152;

Pt(1)-cod(cis to C)cent, 2.048; C(11)-N(3), 1.134(7); C(1)-Pt-(1)-cod(trans to C)avg, 162.3; Cl(1)-

Pt(1)-cod(cis to C)avg, 161.0; C(1)-Pt(1)-cod(cis to C)avg, 94.0.

3.3.5 Nucleophilic Attack of Methoxide on the Coordinated 1,5-Cyclooctadiene Ligand of 7.

Coordinated olefin ligands on palladium and platinum metal complexes are prone to nucleophilic

attack by alkoxides,40 malonates,41 and amines42 to give σ-alkyl complexes or complexes with a

bidentate η1:η2-alkenyl ligand if the olefin is a chelating diene. In order to demonstrate the

reactivity on the coordinated 1,5-cyclooctadiene ligand in 7, we reacted 4 with sodium

methoxide in methanol to deliver a methoxide group onto the olefin ligand. The reaction was

thwarted, however, by instant decomposition of the platinum(II) compound in basic solution,

leading to intractable products. The in situ generation of the methoxide anions by use of

potassium acetate in a methanol solution of 7 under reflux generated the neutral square-planar

complex 8 with 2-methoxycyclooct-5-enyl, C–CN, and chloro ligands (Scheme 3.3). This occurs

via an exo attack of the methoxide anion onto the coordinated diolefin ligand. While the structure

40. (a) Stille, J. K.; Morgan, R. A.; Whitehur, D. D.; Doyle, J. R., J. Am. Chem. Soc. 1965, 87, 3282; (b) Stille, J. K.; Morgan, R. A., J. Am. Chem. Soc. 1966, 88, 5135-5141.41. Tsuji, J.; Takahash.H, J. Am. Chem. Soc. 1965, 87, 3275-3276.42. (a) Cope, A. C.; Kliegman, J. M.; Friedrich, E. C., J. Am. Chem. Soc. 1967, 89, 287-291; (b) Åkermark, B.; Bäckvall, J. E.; Hegedus, L. S.; Zetterberg, K.; Siirala-Hansén, K.; Sjöberg, K., J. Organomet. Chem. 1974, 72, 127-138.

62of the isolated crystals of 8 was characterized as rotamer A, solutions of 8 reveal the presence of

rotamers A and B in equal amounts, as evidenced by NMR spectroscopy (see below). The

retention of the chloro ligand and the formation of both rotamers A and B are unusual

observations for such reactions of palladium(II) and platinum(II) diolefin complexes.28a, 40b

Scheme 3.3. Nucleophilic Attack of Methoxide at the Coordinated Cyclooctadiene Ligand of 7

to 8 and Chloride Abstraction of 8 with AgBF4 in CH3CN to 9a.

The square-planar complex 8 as the exo-R,R rotamer A crystallizes in the chiral triclinic space

group P1 (Figure 3.6, left). The relative orientation of carbene and methoxycyclooctenyl ligands

is similar to that of its palladium analogue (6a). The dihedral angle between the phenyl and the

imidazolylidene rings of the carbene ligand is 58.77°, to relieve sterics between the coordinated

ligands. The Pt–C bond distances of the carbene9b, 33d, 43 (Pt–Ccarbene) and methoxycyclooctenyl28c,

44 (Pt–C(1)) ligands are within expected ranges, while the Pt–Ccarbene bond distance (1.970(1)Å) is

shorter than that of 7 (2.011(5) Å).

43. Ahrens, S.; Herdtweck, E.; Goutal, S.; Strassner, T., Eur. J. Inorg. Chem. 2006, 2006, 1268-1274.44. (a) Goel, A. B.; Goel, S.; Vanderveer, D. G., Inorg. Chim. Acta 1981, 54, L169-L170; (b) Aucott, S. M.; Slawin, A. M. Z.; Woollins, J. D., Dalton Trans. 2000, 2559-2575; (c) Angurell, I.; Martínez-Ruiz, I.; Rossell, O.; Seco, M.; Gómez-Sal, P.; Martín, A.; Font-Bardia, M.; Solans, X., J. Organomet. Chem. 2007, 692, 3882-3891.

NNCH3

Pt

Cl

N

BF4KOAc

CH3CN, rtAgBF4

7 8 9a

PtCl

OCH3NN

N

H3CH

BF4PtN

OCH3NN

N

H3C

H3C

H+ +∆ , CH3OH

63

Figure 3.6. ORTEP diagrams of 8 (left) and 9a (right) depicted with thermal ellipsoids at the

30% probability level. The counteranion and hydrogens have been omitted for clarity. Selected

bond distances (Å) and bond angles (deg): 8 (left): Pt(1)-C(1), 1.969(1); Pt(1)-C(12), 2.095(1);

Pt(1)-Cl(1), 2.430(4); Pt(1)-coe(trans to C)cent, 2.102; C(11)-N(3), 1.135(7); C(19)-O(1),

1.418(2); C-(1)-Pt(1)-coe(trans to C)avg, 160.7; C(12)-Pt(1)-Cl(1), 178.4(4); C(1)-Pt(1)-C(12),

88.9(5). 9a (right): Pt(1)-C(1), 2.001(5); Pt(1)-C(17), 2.044(5); Pt(1)-N(4), 2.122(5); Pt(1)-

coe(trans to C)cent, 2.100; C(10)-N(3), 1.145(8); C(16)-O(1), 1.449(6); C(1)-Pt(1)-coe(trans to

C)avg, 161.0; C(17)-Pt(1)-N(4), 178.3(0); C-(1)-Pt(1)-C(17), 88.9(7).

Complex 8 is soluble in polar solvents such as methanol, acetonitrile, dichloromethane, and

tetrahydrofuran, as well as in aromatic solvents such as benzene and toluene. The absence of the

tetrafluoroborate counteranion is established by the lack of requisite signals in the 19F NMR and

infrared spectra.

A dichloromethane-d2 solution of 8 at 298 K shows a significant downfield shift of the

carbene resonance (Pt–Ccarbene) to 175.8 ppm in the 13C{1H} NMR spectrum compared to the

signal in 7. In addition, the 1H NMR spectrum shows a 1:1 ratio of the methyl resonances for the

carbene (4.05 and 4.02 ppm) and methoxycyclooctenyl ligands (3.05 and 2.95 ppm). In addition,

the H(3) proton of the phenyl ring of the carbene ligand appears as a pair of doublets (3JHH = 7.86

Hz) at 8.66 and 8.39 ppm. Therefore, the complex exists as a 1:1 mixture of rotamers A and B

because of the restricted rotation about the Pt–Ccarbene bond similar to complex 6a. The barrier to

64rotation must be high, because heating a solution of 8 in nitromethane-d3 at 323 K afforded no

change in the 1H NMR spectrum in comparison to that acquired at 298 K. A close examination of

the 13C{1H} NMR spectrum of 8 showed a doubling of all of the resonances in a 1:1 ratio.

Rotamer B is more abundant than that of the palladium(II) complex 6a. Attempts to establish by 1H-1H NOESY NMR spectroscopy the proximity of groups of each rotamer of 8 was not

successful, as no cross-peaks of the relevant protons were observed.

In order to synthesize the platinum(II) analogues of complexes 6a and 6b, we first attempted

to react the silver(I) complex 2a with 1 equiv of [Pt(η1:η2-coe-OMe)(μ-Cl)]2 and AgBF4 in

acetonitrile solutions. These, however, led to intractable products along with decomposition. On

the other hand, adding 1 equiv of AgBF4 to an acetonitrile-d3 solution of 8 afforded the

immediate precipitation of silver chloride. Subsequent filtration gave the white acetonitrile

complex 9a (Scheme 3.3), [Pt(η1:η2-coe-OMe)(C–CN)(CH3CN)]BF4. The carbene carbon

(Pt–Ccarbene) of the NHC ligand was observed as two singlets at 168.9 and 168.7 ppm in a 1:4

ratio in its 13C{1H}NMR spectrum in dichloromethane-d2. All the proton and carbon resonances

of the methoxycyclooctenyl ligand were assigned similarly as with complex 6a on the basis of

the resonance of the C(2) carbon.28c, 43b, 43c In general, the resonances of the platinum(II)

compound appeared at lower frequencies compared to those of its palladium(II) analogue,

consistent with the observation reported by Macchioni and co-workers.28c Again, the presence of

both rotamers A and B in solution are detectable by NMR techniques. In accordance with the

previous assignments made to complexes 6a and 8, we believe there exists at least 20 mol% of

rotamer B in the solution sample of 9a. This is much smaller than the amounts of rotamer B in a

solution for a sample of 8.

Evaporation of the deuterated solvent and slow diffusion of diethyl ether into a solution of 9a

in acetonitrile provided crystals suitable for X-ray diffraction (Figure 3.6, right). The square-

planar complex crystallizes as the exo-R,R rotamer A. The phenyl ring is twisted at a dihedral

angle of 61.36° to the plane of the imidazolylidene ring of the carbene ligand. The acetonitrile

ligand is weakly coordinated (Pt(1)-N(4), 2.122(5)Å) owing to the strong trans influence of the

σ-alkyl group (cf. the average Pt–N distances of other acetonitrile complexes, 2.003Å18). A

comparison of the M–C and M–N distances (M = Pd, Pt) of 6a and 9a reveal similarities in their

magnitudes.

65When 9a was resynthesized in a larger scale and recrystallized in dichloromethane and diethyl

ether mixtures, the corresponding dimer 9b was obtained, analogous to complex 6b (Scheme

3.2). The loss of the acetonitrile ligand was identified by the absence of the resonance at 1.94

ppm in the 1H NMR spectrum in dichloromethane-d2 and the nitrile stretch of acetonitrile in the

infrared spectrum (2227 cm-1). As for the palladium(II) complexes 6a and 6b, there is a decrease

in the nitrile stretching frequency on going from 9a to 9b (2282 to 2262 cm-1). The acetonitrile

complex 9a and the dimeric complex 9b, like 6a and 6b, are interconvertible by using different

recrystallization solvents (Scheme 3.2). Unlike the palladium(II) complexes, the platinum(II)

complexes are stable enough for storage without any precautions taken.

3.3.6 Proposed Reaction Pathways Leading to the Formation of Rotamers A and B of

Complexes 6, 8 and 9. In order to account for the presence of both rotamers A and B in

complexes 6, 8, and 9, and the difference in the distributions of rotamers of complexes 8 and 9, it

is proposed that the carbene ligand can freely rotate in a pentacoordinate complex produced

before the solvent molecule or a chloride ligand that occupies the fifth coordination site of the

square pyramidal complex dissociates. The transmetalation reaction of complex 2a with

[Pd(η1:η2-coe-OMe)(μ-Cl)]2 first forms the transient complex [Pd(η1:η2-coe-OMe)(C–CN)Cl].

The solvent/nitrile ligand then occupies the fifth coordination site of the square-planar complex,

forming a pentacoordinate, possibly a square-pyramidal complex with the carbene ligand

occupying the axial position. The carbene ligand of this intermediate might freely rotate, as the

steric congestion brought about by the 2-methoxycyclooct-5-enyl ligand is relieved. Silver

chloride precipitates from acetonitrile/dichloromethane solutions, forming the square planar

complex 6a. The presence of 80 mol% of rotamer A in solution and the fact that only the single

rotamer A was found in the crystal suggest that this is the thermodynamically preferred product

(Scheme 3.4).

On the other hand, an exo attack by methoxide onto the diolefin of complex 7 occurs at the

double bond that is trans to the chloride ligand. This displaces the chloride ligand and forms a

similar transient complex as the [Pt(η1:η2-coe-OMe)(C–CN)(CH3OH)]+ cation, or it dimerizes

with a bridging group such as the carbene ligand. In this case the coordination of solvated

chloride gives the same pentacoordinate intermediate. Upon dissociation of the coordinated

methanol, which is a poor ligand compared to chloride, this gave the same amounts of rotamers

A and B of 8 in solution. In fact, removal of the chloride ligand from 8 by precipitation using

66silver tetrafluoroborate in acetonitrile gives the same distribution of rotamers (favoring A over

B) of complex 9a as for complex 6a (Scheme 3.4).

Scheme 3.4. Proposed Reaction Pathways Leading to the Formation of Rotamers A and B of

Complexes 6, 8, and 9.

3.3.7 Platinum(II) Complex with Coordinated 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-

ylidene ligand (IMes). For comparison, the analogous coordination chemistry of platinum(II)

was investigated with 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes). The silver(I)

precursor complex [Ag(IMes)2]BF4 (10) was prepared by an established method6 and was reacted

with 2.5 equiv of Pt(cod)Cl2 and 1 equiv of AgBF4 under reflux overnight (Scheme 3.5). The

corresponding complex 11, with coordinated chloro, 1,5-cyclooctadiene, and IMes ligands, was

isolated in 85% yield. Reactions carried out at room temperature did not proceed and recovered

exclusively the starting materials. The carbene carbon (Pt–Ccarbene) was observed as a singlet at

151.4 ppm in the 13C{1H} NMR spectrum in acetonitrile-d3 solution, consistent with that of

complex 7 with a carbene bearing an electron-withdrawing group. Platinum satellites were also

observed at the four olefinic protons and carbons bonded to the metal center (2JPt-H = 22.03 and

31.55 Hz; 1JPt-C = 33.11 and 76.88 Hz), whereas the protons and carbons with smaller coupling

constants are bonded trans to the carbene ligand.36-39 A small coupling of the imidazolylidene

carbon with platinum satellites was also observed (3JPt-C = 16.14 Hz).

M

N

N

N

ClCH3

BF4 CH3OH- KCl- HOAc

+ KCl- CH3OH

M

OCH3NN

N

Cl

CH3

HM

OCH3N

N

N

ClCH3

H

M

H3CON

N

N

CH3H

Cl

M

OCH3NN

N

N

CH3

HM

OCH3N

N

N

NCH3

H

H3C H3CBF4

8: M = PtRotamer A, 50 mol%

8: M = PtRotamer B, 50 mol%

6a: M = Pd; 9a: M = PtRotamer A, Major

6a: M = Pd; 9a: M = PtRotamer B, Minor

OCH3

2

KOAc

AgBF4- AgClCH3CN

BF4M

H3CO

N N

N

CH3

HCl

L

L = CH3OH/CH3CN

CH3OH

+ L AgBF4

-AgClCH3CN

" "

CH2Cl2:CH3CN

+

+ +

BF4

+

+

67Scheme 3.5. Synthesis of Pt(II) Complex 11 from an N-Heterocyclic Carbene Complex of Ag(I)

(10).

When complex 11 was subjected to similar reaction conditions for the synthesis of 8, namely

nucleophilic attack of the coordinated diolefin by methoxide anion, only a trace amount of the

desired product was observed along with the generation of imidazolium salt, 1,3-bis(2,4,6-

trimethylphenyl)imidazolium. On the other hand, reaction of the silver(I) complex 10 with 1

equiv of [Pt(η1:η2-coe-OMe)(μ-Cl)]2 and AgBF4 in refluxing acetonitrile overnight afforded

complex 11, along with trace amounts of the desired product ([Pt(η1:η2-coe-OMe)(IMes)

(CH3CN)]BF4), imidazolium salt, and other decomposition products (Scheme 3.5). All these

results can be attributed to the steric bulk of the IMes ligand directed toward the metal center and

to the methoxycyclooctenyl ligand, therefore destabilizing the metal complex and inducing β-

elimination of H(1) and methoxide of the olefin ligand, generating imidazolium salts and

complex 11, respectively (Scheme 3.5). Attempts to prepare palladium(II) analogues of complex

6 with IMes from the reaction of 10, 1 equiv of [Pd(η1:η2-coe-OMe)(μ-Cl)]2, and AgBF4 was

thwarted by instant decomposition under light and in solutions, in particular, chlorinated

solvents.

Slow diffusion of diethyl ether solutions into the aforementioned reaction mixture in

dichloromethane afforded crystals of complex 11, which were thereby characterized by X-ray

diffraction (Figure 3.7). The slightly distorted square-planar complex crystallizes in the

monoclinic space group Cc with four pairs of asymmetric units residing in the unit cell. The

AgBF4

NN

BF4Ag

NN

[Pt(η 1:η 2-coe-OMe)(µ -Cl)]2

2.5 Pt(cod)Cl2AgBF4

NN

Cl

BF4Pt∆ , CH2Cl2:CH3CN (1:1)

∆ , CH3CN

10

11

NN

Cl

BF4Pt

11Major Minor Minor

NN

BF4BF4

PtN

NN

H3C

OCH3

H

+ +

+++ + +

68carbene ligand that is bonded to the metal center is oriented with the dihedral angles between the

mesityl and imidazolylidene rings of 80.78 and 97.40°. The Pt–Ccarbene bond distance is in the

expected range for most platinum(II) compounds bearing IMes ligands,33a, 33d but is slightly longer

than that of 7 because of its bulkiness. Overall, the metal-carbon bonds of 11 are slightly longer

compared to those of 7.

Figure 3.7. ORTEP diagram of 11⋅0.5 CH2Cl2 depicted with thermal ellipsoids at the 30%

probability level. The counteranion, hydrogens, and solvent molecules have been omitted for

clarity. Only one asymmetric unit is shown. Selected bond distances (Å) and bond angles (deg):

Pt(1A)-C(1A), 2.037(1); Pt(1A)-Cl(1A), 2.315(3); Pt(1A)-cod(trans to C)cent, 2.173; Pt(1A)-

cod(cis to C)cent, 2.084; C(1A)-Pt(1A)-cod(trans to C)avg, 162.3; Cl(1)-Pt(1)-cod(cis to C)avg,

160.9; C(1)-Pt(1)-cod(cis to C)avg, 95.1.

3.4 Conclusion

In summary, we have synthesized and fully characterized new palladium(II) and platinum(II)

complexes bearing chelating olefin and N-heterocyclic carbene ligands. Initial attempts using

silver(I) carbene complex 2a and trans-PdCl2(CH3CN)2 led to the dimeric complex 5a, along

with the partially hydrolyzed trimetallic complex 5b as a side product when wet diethyl ether and

acetonitrile were used as recrystallization solvents. The structure of 5b reveals the presence of a

69novel C–N–N–C donor ligand, comprised of a central –N=C–O–C=N– linkage and two bridging

imido nitrogens.

Platinum(II) complexes with 1,5-cyclooctadiene ligands and N-heterocyclic carbene ligands

(7 and 11) were prepared by transmetalation of the corresponding silver(I) carbene complexes

(2a and 10). The reaction of methoxide with the coordinated diolefin ligand of 7 afforded the

neutral complex 8 and complex 9 upon removal of the chloro ligand. The palladium(II) analogue,

complex 6, was independently prepared by direct transmetalation of 2a and [Pd(η1:η2-coe-OMe

(μ-Cl)]2. Both the monomer and dimer of complexes 6 and 9 were isolated and studied by NMR

and infrared spectroscopy. In addition, reactions leading to complexes 6, 8, and 9 produced

different amounts of rotamers A and B (Figure 3.3), owing to the orientation of C–CN ligand

relative to the 2-methoxycyclooct-5-enyl ligand, and restricted rotation about the M–CCarbene

bond originated from the steric crowding of the 2-methoxycyclooct-5-enyl ligand by the C–CN

ligand. These are the first examples of structurally characterized N-heterocyclic carbene

complexes of palladium(II) and platinum(II) bearing 1,5-cyclooctadiene and 2-methoxy-

cyclooct-5-enyl ligands.


3.5.1 General Considerations. All of the preparations and manipulations, except where

otherwise stated, were carried out under an argon or nitrogen atmosphere using standard

Schlenk-line and glovebox techniques. Dry and oxygen-free solvents were always used.

Deuterated solvents were purchased from Cambridge Isotope Laboratories and Sigma Aldrich

and degassed and dried over activated molecular sieves prior to use. NMR spectra were recorded

on a Varian 400 spectrometer operating at 400 MHz for 1H, 100 MHz for 13C, and 376 MHz for 19F. The 1H and 13C{1H} NMR spectra were measured relative to partially deuterated solvent

peaks but are reported relative to tetramethylsilane (TMS). All 19F chemical shifts were

measured relative to trichlorofluoromethane as an external reference. The 1H-1H NOESY NMR

spectrum of complex 8 was recorded on a Varian 600 spectrometer operating at 600MHz for 1H.

All infrared spectra were recorded on a Nicolet 550 Magna-IR spectrometer. The elemental

analysis was performed at the Department of Chemistry, University of Toronto, on a Perkin-

Elmer 2400 CHN elemental analyzer. Samples were handled under argon where it was

appropriate. Single-crystal X-ray diffraction data were collected using a Nonius Kappa-CCD

70diffractometer with Mo Kα radiation (λ = 0.71073 Å). The CCD data were integrated and scaled

using the Denzo-SMN package. The structures were solved and refined using SHELXTL V6.1.

Refinement was by full-matrix least squares on F2 using all data.

The synthesis of the silver(I) complex, [Ag(C–CN)2]BF4 (2a) was described in Chapter 2.6

The complex [Ag(IMes)2]BF4 (10) was prepared using procedures analogous to those for 2a

from (IMesH)BF4, which was prepared by counteranion metathesis of (IMesH)Cl45 and NH4BF4

in water. The characterization data are similar to those reported in the literature.46 The syntheses

of trans-PdCl2(CH3CN)2,11a Pd(cod)Cl2, Pt(cod)Cl247 and [Pd(η1:η2-coe-OMe)(μ-Cl)]2

24 were

reported in the literature. All other reagents were purchased from commercial sources and were

used as received.

3.5.2 Synthesis of Bis(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)palladium(II)(μ-

dichloro)bis(acetonitrile)palladium(II) Tetrafluoroborate ([(C–CN)2Pd(μ-Cl)2Pd(CH3CN)2]

(BF4)2, 5a). A solution of 2a (39 mg, 0.07 mmol) and silver tetrafluoroborate (14 mg, 0.07

mmol) in acetonitrile (2 mL) was added to a solution of trans-PdCl2(CH3CN)2 (36 mg, 0.14

mmol) in acetonitrile (4 mL). A pale brown precipitate was formed instantaneously. The reaction

mixture continued to be stirred for 2 h. It was then filtered through a pad of Celite to give a

yellow solution. The volume of solvent was reduced (ca. 1 mL), and diethyl ether (8 mL) was

added. The solution was kept at -10°C to give a yellow oil. The supernatant liquid was decanted,

and the oil was triturated with diethyl ether (3 × 3 mL) to give a yellow powder, which was

collected and dried in vacuo. Yield: 39 mg, 62%. Alternatively, the title compound can be

prepared from 2a (75 mg, 0.13 mmol), silver tetrafluoroborate (26 mg, 0.13 mmol), and

Pd(cod)Cl2 (77 mg, 0.27 mmol) using the same procedure. Yield: 96 mg, 79%. 1H

NMR(CD3CN, δ): 8.03 (dd, JHH = 1.58, 7.70 Hz, 3-CH of Ph, 1H), 8.00 (dt, JHH = 1.58, 7.85 Hz,

5-CH of Ph, 1H), 7.89 (dd, JHH = 1.22, 7.85 Hz, 6-CH of Ph, 1H), 7.84 (dt, JHH = 1.22, 7.70 Hz,

4-CH of Ph, 1H), 7.56 (d, JHH = 2.10 Hz, 4-CH of imid, 1H), 7.48 (d, JHH = 2.10 Hz, 5-CH of

imid, 1H), 4.15 (s, CH3 of C–CN, 3H), 1.96 (s, integration cannot be determined because of

exchange with CD3CN,CH3 of CH3CN). 19F NMR (CD3CN, δ): -152.2 (s), -152.3 (s). 13C{1H}

NMR (CD3CN, δ): 141.4 (Pd–C), 140.7 (CPh), 135.4 (CPh), 135.1 (CPh), 131.9 (CPh), 130.7 (CPh),

126.5 (Cimid), 126.2 (Cimid), 118.4 (CN of CH3CN), 116.2 (CN of C–CN), 112.1 (CPh), 38.6 (CH3

45. Arduengo, A. J.; Krafczyk, R.; Schmutzler, R.; Craig, H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M., Tetrahedron 1999, 55, 14523-14534.46. Yu, X.-Y.; Patrick, B. O.; James, B. R., Organometallics 2006, 25, 2359-2363.47 Drew, D.; Doyle, J. R., Inorg. Synth. 1990, 28, 346-349.

71of C–CN), 1.69 (CH3 of CH3CN). IR (KBr, cm-1): 2329 (v(CN) of CH3CN), 2237 (v(CN) of C–

CN). MS(ESI, methanol/water; m/z): 507.0 ([Pd(C–CN)2Cl]+), 471.1 ([Pd(C–CN)2]•+). Anal.

Calcd for C26H24B2Cl2F8N8Pd2: C, 34.47; H, 2.67; N, 12.37. Found: C, 34.74; H, 2.58; N, 12.00.

3.5.3 Synthesis of (Acetonitrile)(1-(2-cyanophenyl)-3-methylimidzol-2-ylidene)(η1:η2-2-

methoxycyclooct-5-enyl)palladium(II) Tetrafluoroborate ([Pd(C–CN)(η1:η2-coe-OMe)

(CH3CN)]BF4, 6a). A solution of 2a (69 mg, 0.12 mmol) and silver tetrafluoroborate (24 mg,

0.12 mmol) in acetonitrile (4 mL) was added to a solution of [Pd(η1:η2-coe-OMe)(μ-Cl)]2 (70

mg, 0.12 mmol) in dichloromethane (6 mL). A white precipitate was formed instantaneously.

The reaction mixture continued to be stirred for 2 h, protected from light. It was then filtered

through a pad of Celite to give a golden yellow solution. The solvent was then removed in vacuo,

and the crude product was recrystallized with acetonitrile (2 mL) and diethyl ether (10 mL) at

-25°C to give white needles. The needles were then collected on a glass frit and dried in vacuo.

Yield: 92 mg, 67%. Alternatively, the title compound can be obtained by recrystallization of 6b

in acetonitrile and diethyl ether. Suitable crystals for an X-ray diffraction study were obtained by

slow diffusion of diethyl ether into a saturation solution of 6a in acetonitrile. In addition to a

peak at 2.01 ppm in the 1H NMR spectrum (CD3NO2), all other spectroscopic information are

identical with those of compound 6b. IR (KBr, cm-1): 2277 (v(CN) of C–CN), 2229 (v(CN) of

CH3CN). MS (ESI, methanol/water; m/z): 428.1 ([M – CH3CN]+). Anal. Calcd for

C22H27BF4N4OPd: C,47.46; H, 4.89; N, 10.06. Found: C, 47.18; H, 4.04; N, 10.26.

3.5.4 Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-methoxy-

cyclooct-5-enyl)palladium(II)] Tetrafluoroborate ([Pd(C–CN)(η1:η2-coe-OMe)]2(BF4)2, 6b).

A solution of 2a (148 mg, 0.26 mmol) and silver tetrafluoroborate (52 mg, 0.27 mmol) in

acetonitrile (4 mL) was added to a solution of [Pd(η1:η2-coe-OMe)(μ-Cl)]2 (149 mg, 0.27 mmol)

in dichloromethane (10 mL). A white precipitate was formed instantaneously. The reaction

mixture continued to be stirred for 2 h, protected from light. The solvent was then removed in

vacuo. The residue was extracted with dichloromethane (10 mL) and filtered through a pad of

Celite to give a golden yellow solution. The solvent was removed, and the crude product was

recrystallized with dichloromethane (2 mL) and diethyl ether (10 mL) to give a white precipitate.

The precipitate was filtered and dried in vacuo to give a white powder. Yield: 210 mg, 77%.

Alternatively, the title compound can be obtained by recrystallization of 6a in dichloromethane

and diethyl ether. 1H NMR (CD3NO2, δ): 8.24 (d, JHH = 7.90 Hz, 3-CH of Ph, 1H), 8.06 (t, JHH =

7.88 Hz, 5-CH of Ph, 1H), 7.88 (t, JHH = 7.90 Hz, 4-CH of Ph, 1H), 7.78 (d, JHH = 7.80 Hz, 6-CH

72of Ph, 1H), 7.66 (d, JHH = 1.86Hz, 4-CH of imid, 1H), 7.54 (d, JHH = 1.86 Hz, 5-CH of imid, 1H),

6.39 (m, 6-CH of olefinic CH, 1H), 6.10 (m, 5-CH of olefinic CH, 1H), 3.91 (d, CH3 of C–CN,

3H), 3.29 (m, 2-CH of coe-OMe, 1H), 2.95 (d, CH3 of coe-OMe, 3H), 2.65 (m, 1A-CH or 1B-

CH and 4-CH of coe-OMe, 1.5H), 2.36 (m, 1A-CH or 1B-CH of coe-OMe, 0.5H), 2.15 (m, 4-CH

and 7-CH of coe-OMe, 2H), 1.91 (m, 3-CH2 of coe-OMe, 2H), 1.77 (m, 7-CH of coe-OMe, 1H),

1.42 (m, 8-CH of coe-OMe, 1H), 0.42 (m, 8-CH of coe-OMe, 1H). 19F NMR (CD3NO2, δ):

-152.9 (s), -153.0 (s). 13C{1H} NMR (CD3NO2, δ): 174.6, 174.2 (Pd–CB/A), 144.5, 144.4

(CPh,B/A), 136.4, 136.0 (CPh,B/A), 134.8, 134.3 (CPh,A/B), 130.5, 130.2 (CPh,B/A), 128.3, 127.9

(CPh,B/A), 124.4, 124.2 (Cimid,B/A), 123.4, 123.2 (Cimid,A/B), 119.5, 119.4 (6-CA/B of coe-OMe),

117.7, 117.4 (CNB/A), 115.4, 115.2 (5-CA/B of coe-OMe), 109.4, 109.1 (CPh,A/B), 81.9, 80.8 (2-

CA/B of coe-OMe), 54.9, 54.8 (CB/A-CH3 of coe-OMe), 41.4, 41.2 (1-CA/B of coe-OMe), 37.5,

37.4 (CA/B-CH3 of C–CN), 33.5, 33.5 (8-CB/A of coe-OMe), 30.1, 29.4 (3-CA/B of coe-OMe),

28.0, 27.6 (4-CA/B of coe-OMe), 24.8, 24.4 (7-CB/A of coe-OMe). IR (KBr, cm-1): 2260 (v(CN) of

C–CN). MS (ESI, methanol/ water; m/z): 428.1 ([0.5 M]+). Anal. Calcd for C40H48B2F8N6O2Pd2:

C, 46.58; H, 4.69; N, 8.15. Found: C, 45.90; H, 5.18; N, 7.82.

3.5.5 Synthesis of Chloro[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene](η4-1,5-cyclo-

octadiene)platinum(II) Tetrafluoroborate ([Pt(C–CN)(cod)Cl]BF4, 7). A solution of 2a (109

mg, 0.19 mmol) and silver tetrafluoroborate (38 mg, 0.19 mmol) in acetonitrile (4 mL) was

added to a solution of Pt(cod)Cl2 (145 mg, 0.39 mmol) in dichloromethane (10 mL). A white

precipitate was formed instantaneously. The reaction mixture continued to be stirred for 2 h. It

was then filtered through a pad of Celite to give a pale yellow solution. The solvent was then

removed in vacuo, and the crude product was recrystallized with dichloromethane (3 mL) at

-25°C to give white crystalline solids. The product was then collected on a glass frit, rinsed with

dichloromethane (2 × 3 mL) and diethyl ether (3 × 3 mL), and dried in vacuo. Yield: 140 mg,

59%. Suitable crystals for an X-ray diffraction study were obtained by slow diffusion of diethyl

ether into a saturation solution of 7 in acetonitrile. 1H NMR (CD3CN, δ): 8.08 (dd, JHH = 1.23,

8.03 Hz, 3-CH of Ph, 1H), 8.03 (dd, JHH = 1.53, 7.70 Hz, 6-CH of Ph, 1H), 8.01 (dt, JHH = 1.53,

8.03 Hz, 4-CH of Ph, 1H), 7.84 (dt, JHH = 1.23, 7.70 Hz, 5-CH of Ph, 1H), 7.68 (d, JHH = 2.10

Hz, 4-CH of imid, 1H), 7.54 (d, JHH = 2.10 Hz, 5-CH of imid, 1H), 5.94 (m, olefinic CH of

codtrans to C, 2H), 5.32 (m, JPt-H = 32.61 Hz, olefinic CH of codtrans to Cl, 1H), 4.35 (m, JPt-H = 30.72

Hz, olefinic CH of codtrans to Cl, 1H), 4.00 (s, CH3, 3H), 2.69 (m, CH2 of cod, 1H), 2.56 (m, CH2

of cod, 1H), 2.38 (m, CH2 of cod, 1H), 2.24 (m, CH2 of cod, 1H), 2.07 (m, CH2 of cod, 1H), 1.72

73(m, CH2 of cod, 1H). 19F NMR (CD3CN, δ): -152.2 (s), -152.3 (s). 13C{1H} NMR (CD3CN, δ):

151.4 (Pt–C), 140.1 (CPh), 135.8 (CPh), 135.6 (CPh), 132.0 (CPh), 130.1 (CPh), 126.5 (Cimid), 125.8

(Cimid), 119.5 (JPt-C = 31.54 Hz, olefinic C of codtrans to C), 119.4 (JPt-C = 31.92 Hz, olefinic C of

codtrans to C), 115.9 (CN), 111.3 (CPh), 97.7 (JPt-C = 75.12 Hz, olefinic C of codtrans to Cl), 94.9 (JPt-C

= 80.20 Hz, olefinic C of codtrans to Cl), 38.6 (CH3), 33.1 (CH2 of cod), 31.7 (CH2 of cod), 29.1

(CH2 of cod), 28.5 (CH2 of cod). IR (KBr, cm-1): 2231 (v(CN)). MS (ESI, methanol/water; m/z):

521.1 ([M]+), 517.2 ([M – Cl + MeOH)]•+), 503.1 ([M – Cl + H2O)]•+). Anal. Calcd for

C19H21BF4ClN3Pt: C, 37.49; H, 3.48; N, 6.90. Found: C, 37.68; H, 3.55; N, 7.14.

3.5.6 Synthesis of Chloro[1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-methoxy-

cyclooct-5-enyl)platinum(II) (Pt(C–CN)(η1:η2-coe-OMe)Cl, 8). A mixture of 7 (100 mg, 0.16

mmol) and potassium acetate (19 mg, 0.19 mmol) were suspended in methanol (12 mL). The

reaction mixture was then refluxed under an argon atmosphere for 3 h to a golden yellow

solution, and all solids were completely dissolved. The solvent was then removed in vacuo. The

residue was extracted with dichloromethane (3 mL) and filtered through a pad of Celite. The

crude product was then recrystallized overnight at -25°C with the addition of n-pentane (15 mL)

to the dichloromethane solution to give white crystalline solids. The product was then collected

on a glass frit and dried in vacuo. Yield: 63 mg, 69%. Suitable crystals for an X-ray diffraction

study were obtained by slow diffusion of diethyl ether into a saturation solution of 8 in

dichloromethane. 1H NMR (CD2Cl2, δ): 8.66 (d, JHH = 7.86 Hz, 3A-CH or 3B-CH of Ph, 0.5H),

8.39 (d, JHH = 7.86 Hz, 3A-CH or 3B-CH of Ph, 0.5H), 7.85 (t, JHH = 7.86 Hz, 4-CH of Ph, 1H),

7.80 (d, JHH = 7.75 Hz, 6-CH of Ph, 1H), 7.61 (dd, JHH = 7.75, 14.37 Hz, 5-CH of Ph, 1H), 7.42

(d, JHH = 1.94 Hz, 4-CH of imid, 1H), 7.23 (d, JHH = 1.94 Hz, 5-CH of imid, 1H), 5.39 (m, JPt-H =

24.46 Hz, 5-CH of olefinic CH, 1H), 5.26 (m, JPt-H = 31.14 Hz, 6-CH of olefinic CH, 1H), 4.05

(s, CH3-A or CH3-B of C–CN, 1.5H), 4.02 (s, CH3-A or CH3-B of C–CN, 1.5H), 3.20 (m, 2A-

CH or 2B-CH of coe-OMe, 0.5H), 3.05 (s, CH3-A or CH3-B of coe-OMe, 1.5H), 2.95 (s, CH3-A

or CH3-B of coe-OMe, 1.5H), 2.71 (m, 4A-CH or 4B-CH of coe-OMe, 1H), 2.57 (m, 4A-CH or

4B-CH of coe-OMe, 1H), 2.28 (m, 1A-CH or 1B-CH of coe-OMe, 0.5H), 2.11 (m, 7A-CH or

7B-CH of coe-OMe, 1H), 1.97 (m, 1A-CH or 1B-CH, 2A-CH or 2B-CH, and 8A-CH or 8B-CH

of coe-OMe, 2H), 1.74 (m, 7A-CH or 7B-CH, and 8A-CH or 8B-CH of coe-OMe, 2H), 1.59 (m,

3A-CH or 3B-CH of coe-OMe, 2H). 13C{1H} NMR (CD2Cl2, δ): 176.2, 175.8 (Pt–CA/B), 142.0,

141.7 (CPh,A/B), 133.9, 133.8 (CPh,A/B), 133.6, 133.5 (CPh,A/B), 130.9, 130.6 (CPh,A/B), 129.8, 129.6

(CPh,A/B), 123.5, 123.3 (Cimid,A/B), 122.2, 122.1 (Cimid,A/B), 116.1, 116.0 (CNA/B), 109.6, 109.5

74(CPh,A/B), 102.9, 101.4 (6-CA/B of coe-OMe), 101.9, 101.2 (5-CA/B of coe-OMe), 83.9, 83.1 (2-

CA/B of coe-OMe), 55.7, 55.6 (CA/B-CH3 of coe-OMe), 38.2, 38.1 (CA/B-CH3 of C–CN), 35.4,

34.1 (3-CA/B of coe-OMe), 29.9, 29.7 (4-CA/B of coe-OMe), 29.6, 29.4 (7-CA/B of coe-OMe),

27.4, 26.9 (8-CA/B of coe-OMe), 22.2, 20.1 (1-CA/B of coe-OMe). IR (KBr, cm-1): 2232 (v(CN)).

MS (ESI, methanol/water; m/z): 517.2 ([M – Cl]+). Anal. Calcd for C20H24ClN3OPt: C, 43.44; H,

4.37; N, 7.60. Found: C, 43.14; H, 4.95; N, 7.92.

3.5.7 Synthesis of (Acetonitrile)(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-

methoxycyclooct-5-enyl)platinum(II) Tetrafluoroborate ([Pt(C–CN)(η1:η2-coe-OMe)

(CH3CN)]BF4, 9a). Complex 8 (11 mg, 0.08 mmol) was dissolved in acetonitrile-d3 (3 mL).

Silver tetrafluoroborate (15 mg, 0.08 mmol) was then added to the reaction mixture, whereupon

a pale brown precipitate was formed instantaneously. The solution was then stirred for 1 h. The

reaction mixture was filtered through a pad of Celite to give a golden yellow solution. 1H NMR

showed quantitative conversion of complex 8 to the title compound. The solution was then

evaporated to dryness to give a yellow oil as the crude product. Suitable crystals for an X-ray

diffraction study were obtained by slow diffusion of diethyl ether into a saturated solution of the

crude product in acetonitrile. In addition to a peak at δ 1.99 ppm in the 1H NMR spectrum

(CD2Cl2), all other spectroscopic data are identical with those for compound 9b. IR (KBr, cm-1):

2282 (v(CN) of C–CN), 2227 (v(CN) of CH3CN). MS (ESI, methanol/water; m/z): 517.2 ([M –

CH3CN]+). HRMS (ESI, methanol/water; m/z): calcd for C20H24N3OPt+ ([M – BF4 – CH3CN]+)

517.1561, found 517.1537.

3.5.8 Synthesis of Bis[(1-(2-cyanophenyl)-3-methylimidazol-2-ylidene)(η1:η2-2-methoxy-

cyclooct-5-enyl)platinum(II)] Tetrafluoroborate ([Pt(C–CN)(η1:η2-coe-OMe)]2(BF4)2, 9b).

Complex 8 (42 mg, 0.08 mmol) was dissolved in acetonitrile (5 mL). Silver tetrafluoroborate (15

mg, 0.08 mmol) was then added to the reaction mixture, whereupon a pale brown precipitate was

formed instantaneously. The solution was then stirred for 1 h. The reaction mixture was filtered

through a pad of Celite to give a golden yellow solution, and the solvent was evaporated to

dryness. The crude product was then recrystallized with dichloromethane (1 mL) and diethyl

ether (8 mL) to give a white precipitate. The precipitate was then collected and dried in vacuo to

give a white powder. Yield: 40 mg, 87%. 1H NMR (CD2Cl2, δ): 8.24 (dd, JHH = 1.56, 7.98 Hz, 3-

CH of Ph, 1H), 7.96 (dt, JHH = 1.56, 7.80 Hz, 5-CH of Ph, 1H), 7.85 (dt, JHH = 1.18, 7.98 Hz, 4-

CH of Ph, 1H), 7.83 (d, JHH = 1.88 Hz, 4-CH of imid, 1H), 7.60 (dt, JHH = 1.18, 7.80 Hz, 6-CH

of Ph, 1H), 7.55 (d, JHH = 1.88Hz, 5-CH of imid, 1H), 5.95 (m, JPt-H = 29.49 Hz, 6-CH of olefinic

75CH, 1H), 5.57 (m, JPt-H = 27.08 Hz, 5-CH of olefinic CH, 1H), 3.80 (d, CH3 of C–CN, 3H), 3.01

(d, CH3 of coe-OMe, 3H), 2.90 (m, 2-CH of coe-OMe, 1H), 2.81 (m, 4A-CH or 4B-CH of coe-

OMe, 1H), 2.52 (m, 4A-CH or 4B-CH of coe-OMe, 1H), 2.16 (m, 8A-CH or 8B-CH of coe-

OMe, 1H), 1.87 (m, 1-CH, 7A-CH or 7B-CH, and 8A-CH or 8B-CH of coe-OMe, 3H), 1.62 (m,

3-CH2 and 7A-CH or 7B-CH of coe-OMe, 3H). 19F NMR (CD3CN, δ): -152.2 (s), -152.3 (s). 13C{1H} NMR (CD2Cl2, δ): 168.9, 168.7 (Pt–CB/A), 141.5, 141.3 (CPh,B/A), 136.7, 136.6 (CPh,A/B),

136.1, 136.0 (CPh,A/B), 131.6, 131.2 (CPh,B/A), 128.8, 128.5 (CPh,B/A), 126.1, 125.7 (Cimid,B/A),

123.8, 123.6 (Cimid,A/B), 118.3, 117.9 (CNB/A), 110.5, 110.4 (CPh,A/B), 109.1, 108.9 (JPt-C = 48.51,

28.31 Hz, 6-CA/B of coe-OMe), 105.7, 104.0 (5-CA/B of coe-OMe), 83.1, 81.5 (2-CA/B of coe-

OMe), 56.0, 54.8 (CA/B-CH3 of coe-OMe), 38.3, 38.1 (CA/B-CH3 of C–CN), 34.4, 33.9 (3-CB/A of

coe-OMe), 29.5 (4-CA/B of coe-OMe), 28.9, 28.2 (7-CA/B of coe-OMe), 26.6, 26.1 (8-CB/A of coe-

OMe), 24.1, 23.9 (1-CA/B of coe-OMe). IR (KBr, cm-1): 2262 (v(CN) of C–CN). MS (ESI,

methanol/water; m/z): 517.2 ([0.5 M]+). Anal. Calcd for C40H48B2F8N6O2Pt2: C, 39.75; H, 4.00;

N, 6.95. Found: C, 39.36; H, 3.91; N, 6.92.

3.5.9 Synthesis of Chloro[1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene)](η4-1,5-cyclo-

octadiene)platinum(II) Tetrafluoroborate ([Pt(IMes)(cod)Cl]BF4, 11). A solution of 10 (106

mg, 0.13 mmol) and silver tetrafluoroborate (26 mg, 0.13 mmol) in acetonitrile (6 mL) was

added to a solution of Pt(cod)Cl2 (123 mg, 0.33mmol) in dichloromethane (6 mL). A white

precipitate was formed instantaneously. The reaction mixture was then refluxed under an argon

atmosphere overnight. The solvent was removed in vacuo after the reaction has gone to

completion. The residue was extracted with acetonitrile (6 mL) and filtered through a pad of

Celite to give a golden yellow solution. The solvent was then removed from vacuum, extracted

with dichloromethane (3 mL), and filtered through a pad of Celite. The crude product was

recrystallized at -25°C with the addition of diethyl ether (15 mL) to the dichloromethane solution

to give tan crystalline solids. The product was then collected on a glass frit and dried in vacuo.

Yield: 163 mg, 85%. 1H NMR (CD3CN, δ): 7.52 (s, CH of imid, 2H), 7.16 (d, 2-CH of Ph, 4H),

5.61 (m, JPt-H = 22.03 Hz, olefinic CH of codtrans to C, 2H), 4.87 (m, JPt-H = 31.55 Hz, olefinic CH

of codtrans to Cl, 2H), 2.39 (s, o-CH3 of Ph,12H), 2.25 (s, p-CH3 of Ph, 6H), 2.25-2.20 (m, CH2 of

cod, 8H). 19F NMR (CD3CN, δ): -152.2 (s), -152.3 (s). 13C{1H} NMR (CD3CN, δ): 151.4 (Pt–C),

142.5 (CPh), 137.3 (CPh), 135.5 (CPh), 134.6 (CPh), 130.8 (CPh), 130.1 (CPh), 127.3 (JPt-C = 16.14

Hz, Cimid), 119.1 (JPt-C = 33.11 Hz, olefinic C of codtrans to C), 96.6 (JPt-C = 76.88 Hz, olefinic C of

codtrans to Cl), 32.6 (CH2 of cod), 28.4 (CH2 of cod), 21.1 (o-C-CH3 of Ph), 19.4 (p-C-CH3 of Ph).

76MS(ESI, methanol/water; m/z): 642.2 ([M]+), 638.3 ([M – Cl + MeOH]•+), 624.3 ([M – Cl +

H2O]•+). Anal. Calcd for C29H36BClF4N2Pt⋅CH2Cl2: C, 44.22; H, 4.70; N, 3.44. Found: C, 44.44;

H, 4.61; N, 3.70.

77Chapter 4: Transmetalation of a Primary Amino-Functionalized N-

Heterocyclic Carbene Ligand from an Axially Chiral Square-Planar

Nickel(II) Complex to Ruthenium(II) and Osmium(II) Catalysts for

the Hydrogenation of Polar Bonds

4.1 Abstract

The first homoleptic nickel(II) complex with primary amino-functionalized N-heterocyclic

carbene (C–NH2) ligands ([Ni(C–NH2)2](PF6)2, 12) was prepared under mild conditions by the

reduction of a nitrile-functionalized imidazolium salt 1a. This axially chiral, square-planar

nickel(II)complex was characterized by NMR spectroscopy and an X-ray diffraction study.

Enantiopure Δ-TRISPHAT was used as an NMR chiral shift reagent to observe the

diastereotopic ion pairs by 1H NMR in acetonitrile-d3. A novel transmetalation reaction moved

the C–NH2 ligand from the nickel(II) complex 12 to the [M(p-cymene)Cl2]2 dimers (M = Ru,

Os), yielding the ruthenium(II) and osmium(II) complexes [M(p-cymene)(C–NH2)Cl]PF6, (13,

M = Ru; 14, M = Os), the first ruthenium(II) and osmium(II) complexes with such a chelating C–

NH2 ligand. Complex 13 is a catalyst for the transfer hydrogenation of acetophenone to 1-

phenylethanol in basic 2-propanol at 75°C with a turnover frequency (TOF) of up to 880 h-1 and

a conversion of 96%. The complex [RuCp*(C–NH2)(py)]PF6 (15), on the other hand, was

prepared from the transmetalation reaction of complex 12 and RuCp*(cod)Cl, and subsequent

addition of pyridine (cod = η4-1,5-cyclooctadiene, py = pyridine). This complex is an active

catalyst for the H2-hydrogenation of ketones, an epoxide, ester and ketimine in basic solution. A

maximum TOF of 17 600 h-1 is achieved under mild reaction conditions (25°C) and economical

use of hydrogen (8 bar) while the TOF of a related complex with a 2-(diphenylphosphino)-

benzylamine ligand (P–NH2), [RuCp*(P–NH2)(py)]PF6 (16a), is much smaller.

*Reproduced in part with permission from O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 6755-6761. Copyright 2009 American Chemical Society.*O, W. W. N.; Lough, A. J.; Morris, R. H., Chem. Commun. 2010, 46, 8240 – 8242. Reproduced in part by the permission of The Royal Society of Chemistry (RSC). http://pubs.rsc.org/en/content/articlelanding/2010/cc/ c0cc02664f

http://pubs.rsc.org/en/content/articlelanding/2010/cc/

http://pubs.rsc.org/en/content/articlelanding/2010/cc/c0cc02664f

http://pubs.rsc.org/en/content/articlelanding/2010/cc/c0cc02664f

784.2 Introduction

A powerful concept in the design of homogeneous hydrogenation catalysts is the heterolytic

splitting of dihydrogen1 across a transition metal–amido bond.2 This provides a bifunctional

metal–hydride and protic amine grouping for the efficient, selective reduction of polar bonds to

produce valuable alcohols and amines.2 Ruthenium(II) complexes bearing a phosphine–amine

ligand (P–NH2) that catalyze efficiently the hydrogenation of ketones,3 imines,4 esters5 and other

polar bonds6 may utilize this mechanism.

The notion of replacing a phosphine with an N-heterocyclic carbene (NHC) donor is attractive

with the promise of a reduction in the toxicity of catalyst precursors and contaminants in the

hydrogenated products.7 The use of donor-functionalized N-heterocyclic carbenes as ligands in

the design of homogeneous catalysts is of particular interest as they provide coordination

versatility and metal-ligand bifunctionality that will enhance catalytic activity.8 Among those,

both secondary and tertiary amino-functionalized NHC ligands are found to be important

building blocks of active transition metal catalysts that are used for cross-coupling and

hydrosilylation reactions (Figure 4.1).9

1. (a) Morris, R. H., Can. J. Chem. 1996, 74, 1907-1915; (b) Ito, M.; Ikariya, T., Chem. Commun. 2007, 5134-5142; (c) Kubas, G. J., Chem. Rev. 2007, 107, 4152-4205.2. (a) Clapham, S. E.; Hadzovic, A.; Morris, R. H., Coord. Chem. Rev. 2004, 248, 2201-2237; (b) Ikariya, T.; Murata, K.; Noyori, R., Org. Biomol. Chem. 2006, 4, 393-406; (c) Ikariya, T., Bull. Chem. Soc. Jpn. 2011, 84, 1-16.3. (a) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529; (b) Jia, W. L.; Chen, X. H.; Guo, R. W.; Sui-Seng, C.; Amoroso, D.; Lough, A. J.; Abdur-Rashid, K., Dalton Trans. 2009, 8301-8307; (c) Phillips, S. D.; Fuentes, J. A.; Clarke, M. L., Chem.-Eur. J. 2010, 16, 8002-8005.4. Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579.5. (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P., Angew. Chem. Int. Ed. 2007, 46, 7473-7476; (b) Clarke, M. L.; Diaz-Valenzuela, M. B.; Slawin, A. M. Z., Organometallics 2007, 26, 16-19; (c) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saito, T., Adv. Synth. Catal. 2010, 352, 92-96.6. (a) Ito, M.; Hirakawa, M.; Osaku, A.; Ikariya, T., Organometallics 2003, 22, 4190-4192; (b) Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T., J. Am. Chem. Soc. 2007, 129, 290-291; (c) Ito, M.; Kobayashi, C.; Himizu, A.; Ikariya, T., J. Am Chem Soc. 2010, 132, 11414-11415.7. (a) Hahn, F. E.; Jahnke, M. C., Angew. Chem. Int. Ed. 2008, 47, 3122-3172; (b) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676.8. (a) Kuhl, O., Chem. Soc. Rev. 2007, 36, 592-607; (b) Liddle, S. T.; Edworthy, I. S.; Arnold, P. L., Chem. Soc. Rev. 2007, 36, 1732-1744; (c) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (d) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (e) Poyatos, M.; Mata, J. A.; Peris, E., Chem. Rev. 2009, 109, 3677-3707; (f) Corberan, R.; Mas-Marza, E.; Peris, E., Eur. J. Inorg. Chem. 2009, 1700-1716.9. (a) Douthwaite, R. E.; Houghton, J.; Kariuki, B. M., Chem. Commun. 2004, 698-699; (b) Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R.; Houghton, J.; Kariuki, B. M.; Simonovic, S., Dalton Trans. 2004, 3528-3535; (c) Houghton, J.; Dyson, G.; Douthwaite, R. E.; Whitwood, A. C.; Kariuki, B. M., Dalton Trans. 2007, 3065-3073; (d) Jong, H.; Patrick, B. O.; Fryzuk, M. D., Can. J. Chem. 2008, 86, 803-810; (e) Jimenez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A., Organometallics 2008, 27, 224-234; (f) Wei, W.; Qin, Y.; Luo, M.; Xia, P.; Wong, M. S., Organometallics 2008, 27, 2268-2272; (g) Jong, H.; Patrick, B. O.; Fryzuk, M. D., Organometallics 2011, 30, 2333-2341.

79We are interested in the design of late transition metal catalysts for polar bond hydrogenation

with chelating primary amino-functionalized NHC (C–NH2) ligands that resemble those of the

highly active phosphine-amine analogues to achieve greener catalysis. This is synthetically

challenging since free NHC are known to react with amines,10 and the syntheses of these

imidazolium salt precursors were thwarted by their low yields.11 We show in this chapter that a

nitrile-functionalized N-heterocyclic carbene ligand12 provides direct access to such a C–NH2

ligand by the reduction of a nitrile-functionalized imidazolium salt under mild conditions. Once

attached to nickel(II), this new type of C–NH2 ligand can be moved to ruthenium(II)13 and

osmium(II)14 in an efficient transmetalation reaction to yield catalysts for the transfer

hydrogenation of ketone, and H2-hydrogenation of a variety of molecules with polar bonds.15 The

ruthenium(II) complex containing a phosphine-amine (P–NH2 = 2-(diphenylphosphino)-

benzylamine herein) and pentamethylcyclopentadienyl ligand (Cp*) ligands was also prepared

for comparison.15 The related complex RuCp*(κ2(P,N)-PPh2CH2CH2NH2)Cl (16b), was prepared

in situ by Ikariya and co-workers.6a, 16

Figure 4.1. Examples of transition metal complexes bearing amino-functionalized N-

heterocyclic carbene ligands reported by Douthwaite and Oro. See references 9a, 9b and 9e.

4.3. Results and Discussion

4.3.1 Reduction of a Nitrile-Functionalized Imidazolium Salt to the First Homoleptic

Primary Amino-Functionalized N-Heterocyclic Carbene Complex of Nickel(II). Caddick et

10. (a) Enders, D.; Breuer, K.; Raabe, G.; Runsink, J.; Teles, J. H.; Melder, J. P.; Ebel, K.; Brode, S., Angew. Chem. Int. Ed. 1995, 34, 1021-1023; (b) Frey, G. D.; Lavallo, V.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G., Science 2007, 316, 439-441.11. Busetto, L.; Cassani, M. C.; Femoni, C.; Macchioni, A.; Mazzoni, R.; Zuccaccia, D., J. Organomet. Chem. 2008, 693, 2579-2591.12. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 853-862.13. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 6755-6761.14. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2011, 30, 1236-1252.15. O, W. W. N.; Lough, A. J.; Morris, R. H., Chem. Commun. 2010, 46, 8240 - 8242.16. Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T., Organometallics 2001, 20, 379-381.

NN

N

RRh

N

N N N

NR R

Pd

ClN

NPh

nPr

NPd

ClClHH

H+ +

80al. and Khurana and Kukreja have reported the use of nickel(II) chloride and sodium borohydride

in alcoholic solvents to reduce both aromatic and aliphatic nitriles to primary and secondary

amines or to protected primary amines in high yields under mild conditions.17 We attempted to

synthesize amino-functionalized imidazolium salts by the reduction of the corresponding nitriles

by use of such an established procedure.17a The reaction of a stoichiometric amount of hydrated

nickel(II) chloride and imidazolium salt 1a (Scheme 4.1) with an excess of sodium borohydride

at low temperature produced an intractable mixture of products; nevertheless all of the

imidazolium salt 1a was consumed. An aqueous workup of the reaction mixture in air, followed

by counteranion metathesis with NH4PF6 in water, afforded a yellow solid, which was

characterized as the first homoleptic primary amino-functionalized N-heterocyclic carbene

complex of nickel(II) ([Ni(C–NH2)2](PF6)2, 12) in about 20% yield based on 1a. The reaction

conditions were further optimized by using anhydrous nickel(II) chloride to improve the purity

of the product. The yield was increased to 30% by carrying out the reduction under a hydrogen

atmosphere and using large volumes of methanol to dissolve the imidazolium salt, which

otherwise has limited solubility (Scheme 4.1). A hydrogen atmosphere is not a prerequisite for

the reduction to occur although a drop of the isolated yield of up to 5% was observed. To our

knowledge, there are only two primary amino-functionalized N-heterocyclic carbene complexes,

those of silver bromide and palladium dichloride reported by Douthwaite and co-workers.9b Only

a few crystals of the palladium(II) complexes containing a chelating C–NH2 ligand were

synthesized by slow hydrolysis of an imine linkage. Williams and co-workers reported the use of

primary amino-functionalized imidazolium salts in enantioselective copper-catalyzed conjugate

addition reactions.18 None of these copper complexes, however, were fully characterized or

isolated.

Scheme 4.1. Synthesis of a Homoleptic Primary Amino-Functionalized N-Heterocyclic Carbene

Complex of Nickel(II) (12).

17. (a) Caddick, S.; Haynes, A. K. D.; Judd, D. B.; Williams, M. R. V., Tetrahedron Lett. 2000, 41, 3513-3516; (b) Khurana, J. M.; Kukreja, G., Synth. Commun. 2002, 32, 1265-1269; (c) Caddick, S.; Judd, D. B.; Lewis, A. K. D.; Reich, M. T.; Williams, M. R. V., Tetrahedron 2003, 59, 5417-5423.18. Moore, T.; Merzouk, M.; Williams, N., Synlett 2008, 21-24.

1) NiCl2, CH3OH2) 7 NaBH4, -78

°C, Ar or H23) NH4PF6, H2O, rt

0.5

N

N N CH3

BF4

+

Ni

NN

N N

NN

H3CCH3

2+

(PF6)2

H H H H1a 12

81Complex 12 has been structurally characterized by the use of X-ray diffraction (Figure 4.2).

The complex crystallizes in the orthorhombic chiral space group P212121 with four units residing

in the unit cell. The structure shows a square-planar geometry about the metal center, with C(1)-

Ni(1)-N(5) and C(1)-Ni(1)-C(12) bond angles of 91.8 and 88.1°, respectively. The Ni–Ccarbene

bond distances are typical of analogous cationic nickel(II) NHC systems.19 The Ni–Namine bond

distances are slightly longer than those of a nickel(II)-(2-methyl-1,2-propanediamine) complex

(1.913 Å)20 because of the higher trans influence of the carbene ligand. The amino protons on the

carbene ligands were hydrogen bonded to the fluorine atoms of the hexafluorophosphate anions

at distances between 2.18 and 2.60 Å.13 The phenyl rings are twisted with respect to the

imidazolylidene ring at dihedral angles of 52.76 and 55.01° to facilitate chelation.


counteranions and most of the hydrogens have been omitted for clarity. Selected bond distances

(A° ) and bond angles (deg): Ni(1)-C(1), 1.870(6); Ni(1)-C(12), 1.883(6); Ni(1)-N(5), 1.963(5);

Ni(1)-N(6), 1.937(5); C(1)-Ni(1)-N(5), 91.8(3); C(1)-Ni(1)-C(12), 88.1(3).

Furthermore, the identity of the title compound was established by the observation of a sharp

singlet in the 13C{1H} NMR spectrum in acetonitrile-d3 solution at 159.0 ppm assigned to the

carbene carbon (Ni–Ccarbene), which is in the expected range for analogous cationic nickel(II)

NHC systems.19 The identity of the complex was further established by the disappearance of a 19. (a) Wang, X.; Liu, S.; Jin, G. X., Organometallics 2004, 23, 6002-6007; (b) Winston, S.; Stylianides, N.;

Tulloch, A. A. D.; Wright, J. A.; Danopoulos, A. A., Polyhedron 2004, 23, 2813-2820; (c) Xi, Z.; Zhang, X.; Chen, W.; Fu, S.; Wang, D., Organometallics 2007, 26, 6636-6642; (d) Shibata, T.; Ito, S.; Doe, M.; Tanaka, R.; Hashimoto, H.; Kinoshita, I.; Yano, S.; Nishioka, T., Dalton Trans. 2011, 40, 6778-6784.20. (a) García-Granda, S.; Beurskens, P. T.; Behm, H. J. J.; Gómez-Beltrán, F., Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1987, 43, 236-238; (b) García-Granda, S.; Díaz, M. R.; Gómez-Beltrán, F., Acta Crystallogr. Sect. C: Cryst. Struct. Commun. 1990, 46, 598-600.

82broad resonance at 2.80 ppm upon addition of D2O to a solution of 12, as a result of complete

deuteration of the coordinated amino groups of the carbene ligands.

4.3.2 Solution NMR Studies of the Axial Chirality of the Homoleptic Primary Amino-

Functionalized N-Heterocyclic Carbene Complex of Nickel(II). The solid state structure of

complex 12 reveals that the metal complex is axially chiral about the two chelating ligands,

analogous to a 1,1ꞌ-binaphthyl linkage, but where the chiral and C2 rotational axes pass through

the metal center, lying in the same plane as the carbene carbon and amine nitrogen atoms. In

solution, the racemic mixture of complex 12 shows two diastereotopic protons on the methylene

linker at 2.53 and 3.56 ppm, as a result of the chirality established on the 3-methyl-

imidazolylidene rings. Chiral square-planar complexes with no stereogenic centers on the

coordinating ligands are rare. Mills and Quibell have reported the first optically resolved square-

planar complex of platinum(II) with meso-1,2-diphenylethylenediamine (dpen) and 1,1-

dimethylethylenediamine ligands, but these have carbon stereocenters.21 Thereafter, there were

reports of chiral square-planar complexes of pyridines without stereogenic centers, some of

which have been optically resolved.22 Attempts to resolve the two enantiomers of 12, for

example, by sodium L-tartrate failed, as indicated by circular dichroism (CD) spectra of the

isolated solids.

The use of enantiopure Δ-TRISPHAT as a NMR chiral shift reagent allows the observation of

diastereotopic ion pairs if the nickel(II) cation is configurationally stable on the time scale of the

NMR experiment.23 In this case the lifetime of the diastereomers must be greater than the inverse

of the chemical shift difference (in Hz) between resonances of the diastereomers. The addition of

2 equiv of [Bu4N][Δ-TRISPHAT] to an acetonitrile-d3 solution of complex 12 caused

diamagnetic shifting and doubling of the resonances of the methyl and imidazolylidene ring

protons in the 1H NMR spectrum. The integration of signals remained in a ratio of 1:1 as

expected starting with a configurationally stable racemic mixture (Figure 4.3). The spectra are

consistent with an ion pair structure with the Δ-TRISPHAT anion located near the 3-methyl-

21. Mills, W. H.; Quibell, T. H. H., J. Chem. Soc. 1935, 839-846.22. (a) Gianini, M.; Forster, A.; Haag, P.; von Zelewsky, A.; Stoeckli-Evans, H., Inorg. Chem. 1996, 35, 4889-4895; (b) Biagini, M. C.; Ferrari, M.; Lanfranchi, M.; Marchio, L.; Pellinghelli, M. A., Dalton Trans. 1999, 1575-1580.23. (a) Lacour, J.; Ginglinger, C.; Favarger, F.; Torche-Haldimann, S., Chem. Commun. 1997, 2285-2286; (b) Lacour, J.; Frantz, R., Org. Biomol. Chem. 2005, 3, 15-19 and references therein; (c) Lacour, J., C. R. Chim. 2010, 13, 985-997 and references therein.24. (a) Macchioni, A., Chem. Rev. 2005, 105, 2039-2073 and references therein; (b) Macchioni, A.; Ciancaleoni, G.; Zuccaccia, C.; Zuccaccia, D., Chem. Soc. Rev. 2008, 37, 479-489.

83imidazolylidene rings. Such stable ion pair structures have been reported by Macchioni and co-

workers.24 No diamagnetic shifting and doubling of the resonances were observed in dimethyl

sulfoxide-d6 solution, which disfavors ion pairing.

Figure 4.3. Selected sections of the 1H NMR spectra of complex 12 in acetonitrile-d3 (400 MHz,

298 K) and the assignments of the imidazolylidene ring (left) and methyl protons (right) in the

presence of (a) 0 equiv, (b) 1 equiv, (c) 2 equiv, and (d) 3 equiv of [Bu4N][Δ-TRISPHAT].

The doubling of peaks, however, is not consistent with mixed PF6/Δ-TRISPHAT ion pair

structures because the integrations of the doubled peaks remained unchanged as the

concentration of [Bu4N][Δ-TRISPHAT] increased. Indeed there will be a fast exchange of ion

pairs in solution, leading to an average of the NMR properties of these mixed anion structures.

However, diastereotopic diamagnetic shielding contributed by Δ-TRISPHAT in these structures

clearly increased as the [Bu4N][Δ-TRISPHAT] concentration increased, as expected (Figure 4.3).

844.3.3 Transmetalation Reaction of a Primary Amino-Functionalized N-Heterocyclic

Carbene from Nickel(II) to Ruthenium(II) and Osmium(II) Complexes with an Arene

ligand. The transmetalation reaction to move the chelating C–NH2 ligand from complex 12 to

the ruthenium(II) or osmium(II) dimers [M(p-cymene)Cl2]2 (M = Ru, Os) in refluxing

acetonitrile solution afforded a deep green solution after 2.5 h (Scheme 4.2). Subsequent

extraction with tetrahydrofuran (THF) or dichloromethane and recrystallization afforded yellow-

colored solids, which were characterized as [M(p-cymene)(C–NH2)Cl]PF6 (13, M = Ru; 14, M =

Os) by NMR spectroscopy and X-ray diffraction study (Figures 4.4 and 4.5). Complex 13 is an

air-stable solid, but it slowly decomposes in solution under prolonged exposure to air. Complex

14 is infinitely stable in both solid state and in solution. To our knowledge, these are the first

group 8 metal complexes bearing a primary amino-functionalized N-heterocyclic carbene ligand.

Scheme 4.2. Synthesis of Complexes 13 and 14 Bearing the C–NH2 Ligand by the

Transmetalation Reaction Involving Complex 12 and [M(p-cymene)Cl2]2 (M = Ru, Os).

Complex 13 crystallizes in the orthorhombic chiral space group Pbca, with four pairs of

enantiomers residing in the unit cell, as the metal complex is chiral about the ruthenium(II)

center (Figure 4.4). The structure has a piano-stool geometry about the metal center with a planar

arene ring coordinated to the metal center in an η6 fashion. The Ru–Ccarbene bond distance is

typical of analogous ruthenium(II) complexes of the form [Ru(η6-arene)(NHC)D2]n+ (D = halides

or mixed neutral/halide ligands, n = 0 or +1).25 The Ru–Namine bond distance is comparable to

known bifunctional catalysts for polar bond hydrogenation with the general formula [Ru(η6

25. (a) Geldbach, T. J.; Laurenczy, G.; Scopelliti, R.; Dyson, P. J., Organometallics 2006, 25, 733-742; (b) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Toupet, L.; Castarlenas, R.; Fischmeister, C.; Dixneuf, P. H., Eur. J. Inorg. Chem. 2007, 2862-2869; (c) Ozdemir, I.; Demir, S.; Gurbuz, N.; Cetinkaya, B.; Toupet, L.; Bruneau, C.; Dixneuf, P. H., Eur. J. Inorg. Chem. 2009, 1942-1949; (d) Gandolfi, C.; Heckenroth, M.; Neels, A.; Laurenczy, G.; Albrecht, M., Organometallics 2009, 28, 5112-5121; (e) Horn, S.; Gandolfi, C.; Albrecht, M., Eur. J. Inorg. Chem. 2011, 2863-2868.26. (a) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R., J. Am. Chem. Soc. 1995, 117, 7562-7563; (b) Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R., Angew. Chem. Int. Ed. 1997, 36, 285-288; (c) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R., J. Am. Chem. Soc. 1996, 118, 4916-4917; (d) Hannedouche, J.; Clarkson, G. J.; Wills, M., J. Am. Chem. Soc. 2004, 126, 986-987; (e) Hayes, A. M.; Morris, D. J.; Clarkson, G. J.; Wills, M., J. Am. Chem. Soc. 2005, 127, 7318-7319.

[M(p-cymene)Cl2]2∆ , CH3CN

Ni

NN

N N

NN

H3CCH3

2+

(PF6)2

H H H H

MCl NNN

CH3

HH

PF6

13: M = Ru;14: M = Os

+

12

85-arene)(diamine)X] (X = halides).26 Similar to complex 12, the amino protons on the carbene

ligand were hydrogen bonded to the fluorine atom of the hexafluorophosphate anion and the

oxygen atom of the solvent tetrahydrofuran molecule at distances between 2.06 and 2.36 Å.13

The phenyl ring is twisted with respect to the imidazolylidene ring at a dihedral angle of 54.59°,

and the seven-membered ring with –Ru(1)–C(1)–N(2)–C(5)–C(10)–C(11)–N(3)– linkage is

nonplanar.

Figure 4.4. ORTEP diagram of 13⋅THF depicted with thermal ellipsoids at 30% probability. The

counteranion, solvent molecule, and most of the hydrogens have been omitted for clarity.

Selected bond distances (Å) and bond angles (deg): Ru(1)-C(1), 2.092(5); Ru(1)-N(3), 2.146(4);

Ru(1)-Cl(1), 2.4180(13); Ru(1)-C(15), 2.248(5); C(1)-Ru(1)-N(3), 91.98(17); C(1)-Ru(1)-Cl(1),

88.24(13); Cl(1)-Ru(1)-N(3), 81.81(11).

The structurally similar osmium(II) complex 13 showed a piano-stool geometry about the

metal center in its solid state structure (Figure 4.5) with an η6-cymene ligand and the chloro and

the chelating C–NH2 ligands. The Os–Ccarbene bond (2.07(1) Å) is comparable to those in

compounds containing an NHC ligand reported in the literature.27 Similar to complex 12, the

phenyl ring is twisted with respect to the imidazolylidene ring at a dihedral angle of 51.70° to

facilitate chelation.

86

Figure 4.5. ORTEP diagram of 14 depicted with thermal ellipsoids at the 30% probability level.


distances (Å) and bond angles (deg): Os(1)-C(1), 2.07(1); Os(1)-N(3), 2.137(9); Os(1)-Cl(1),

2.422(3); Os(1)-C(15), 2.201(6); C(1)-Os(1)-N(3), 91.1(4); C(1)-Os(1)-Cl(1), 87.5(3); Cl(1)-

Os(1)-N(3), 80.0(3).

In dichloromethane-d2 solution, the carbene carbon Ru–Ccarbene and Os–Ccarbene were observed

as a singlet at 175.1 and 159.4 ppm in the 13C{1H} NMR spectrum, respectively. They are in the

expected range for analogous ruthenium(II)25d, 25e, 28 and osmium(II)27 complexes. Complete

deuteration of the amino protons of the chelating carbene ligand in complex 13 by D2O was

observed by the disappearance of two broad multiplets at 5.12 and 3.68 ppm in the 1H NMR

spectrum.

The use of enantiopure Δ-TRISPHAT is again useful to observe the diastereotopic ion pairs

originating from the presence of two enantiomers in solution. Thus the addition of 1 equiv of

[Bu4N][Δ-TRISPHAT] to a dichloromethane-d2 solution of complex 13 caused diamagnetic

27. (a) Castarlenas, R.; Esteruelas, M. A.; Onate, E., Organometallics 2005, 24, 4343-4346; (b) Eguillor, B.; Esteruelas, M. A.; Olivan, M.; Puerta, M., Organometallics 2008, 27, 445-450; (c) Castarlenas, R.; Esteruelas, M. A.; Lalrempuia, R.; Olivan, M.; Onate, E., Organometallics 2008, 27, 795-798; (d) Castarlenas, R.; Esteruelas, M. A.; Onate, E., Organometallics 2008, 27, 3240-3247. 28. (a) Arnold, P. L.; Scarisbrick, A. C., Organometallics 2004, 23, 2519-2521; (b) Csabai, P.; Joo, F., Organometallics 2004, 23, 5640-5643.

87shifting and doubling of the resonances of the imidazolylidene ring protons and complete

splitting of the C(2) proton of the η6-arene ring in the 1H NMR spectrum, while the relative

integration of the split peaks remained in a ratio of 1:1 even when the concentration of [Bu4N]

[Δ-TRISPHAT] increased (Figure 4.6). Of note, an increase in the concentration of [Bu4N][Δ-

TRISPHAT] caused a diamagnetic shifting of the NH proton, which is not observed in the same

experiment with complex 12. A loss of the hydrogen bonding between the amino protons and the

hexafluorophosphate anion and an increase in the shielding effect of the amino protons by the

ring-current induced by the arene rings of the Δ-TRISPHAT anion might be responsible for such

an observation. However, the observed diamagnetic shifting and doubling of the resonances of

the protons of the 3-methylimidazolylidene ring, the amino group, and parts of the arene ligand

indicate that the Δ-TRISPHAT anion takes up various positions of ion pairing and rapidly moves

between these locations to produce averaged NMR properties. The methyl protons of the

isopropyl group of the η6-arene ligand are least affected by the addition of up to 3 equiv of

[Bu4N][Δ-TRISPHAT] (Figure 4.6). Similar to the case of complex 12, the extent of the

diastereotopic diamagnetic shielding of the protons in 13 caused by Δ-TRISPHAT increased as

the anion concentration increased, and this dominated over effects caused by anion exchange

between the various ion pairs and solvated anions.

88

Figure 4.6. Selected sections of the 1H NMR spectra of complex 13 in dichloromethane-d2 (400

MHz, 298 K) and the assignments of the imidazolylidene ring (left), p-cymene ring (middle) and

the isopropyl-methyl protons (right) in the presence of (a) 0 equiv, (b) 1 equiv, (c) 2 equiv, and

(d) 3 equiv of [Bu4N][Δ-TRISPHAT].

4.3.4 Synthesis of a Ruthenium(II) Complex with a Primary Amino-Functionalized N-

Heterocyclic Carbene and Pentamethylcyclopentadienyl ligands. The transmetalation

reaction between 12 and 1.5 equiv. of RuCp*(cod)Cl (cod = 1,5-cyclooctadiene) in acetonitrile,

and subsequent workup in THF and excess pyridine afforded complex 15 in 64% yield as

oxygen-sensitive orange-red needles (Scheme 4.3). Of note, the use of 2 equiv. of RuCp*(cod)Cl

and subsequent workup in THF and toluene mixtures afforded crystallization of small amounts

of [RuCp*(η6-toluene)]PF6 as a side product.29 The phosphine-amine complex 16a was

synthesized from the reaction of 2-(diphenylphosphino)benzylamine30 and RuCp*(cod)Cl in

dichloromethane. Subsequent halide abstraction with AgPF6 and addition of excess pyridine at

89ambient temperature (25°C) afforded a moderately oxygen-sensitive yellow solid in 67% yield

(Scheme 4.3).

Scheme 4.3. Synthesis of the Ruthenium(II) Complexes Containing the C–NH2 (15) and P–NH2

(l6a) Ligands.

Complexes 15 and 16a were unambiguously characterized by X-ray diffraction studies

(Figures 4.7 and 4.8). Both complexes adopt a piano-stool geometry about the ruthenium center,

with the corresponding chelating and pyridine ligands. The Ru–Ccarbene bond (2.03(1) Å) in 15 is

shorter than that of complex 13 (2.092(5)Å),13 but in the expected range of analogous

RuCp*(NHC)L2 complexes.25d, 31 The Ru–PPh2 bond length is similar to those reported by

Ikariya and co-workers.32

Diagnostic NMR features include the Ru–Ccarbene resonance at 198.0 ppm in the 13C{1H}

NMR spectrum of complex 15 in acetone-d6 and the PPh2 peak at 44.7 ppm as a singlet in the 31P{1H} NMR spectrum of 16a in dichloromethane-d2. These complexes demonstrate fluxional

behaviour at ambient temperature (25°C) due to restricted rotation of the Ru–Npyridine bond.

Cooling these samples to -40°C allows the observation of the aromatic protons, as well as the

diastereotopic protons for the CH2 linker between the primary amine group and the phenylene

spacer.15

29. O, W. W. N.; Lough, A. J.; Morris, R. H., Acta Crystallogr. Sect. E: Struct Rep. Online 2010, 66, m1264.30. Cahill, J. P.; Bohnen, F. M.; Goddard, R.; Kruger, C.; Guiry, P. J., Tetrahedron: Asymmetry 1998, 9, 3831-3839.31. (a) Baratta, W.; Herdtweck, E.; Herrmann, W. A.; Rigo, P.; Schwarz, J. D., Organometallics 2002, 21, 2101-2106; (b) Miranda-Soto, V.; Grotjahn, D. B.; Cooksy, A. L.; Golen, J. A.; Moore, C. E.; Rheingold, A. L., Angew. Chem. Int. Ed. 2011, 50, 631-635.32. Ito, M.; Osaku, A.; Kobayashi, C.; Shiibashi, A.; Ikariya, T., Organometallics 2009, 28, 390-393.

1.5 RuCp*Cl(cod)∆ , CH3CN

xs pyridine Ru

NN

N

CH3 PF6N1.5HH

NiN

NN N

NN

H3CCH3

2+

(PF6)2

H H H H

NH2 PPh2RuCp*Cl(cod) Ru

PPh2NPF6N

CH2Cl2, rt

1) AgPF6, CH3CN, rt2) xs pyridine, THF, rt

HH

15

16a

12

THF, rt

+

+

90


counteranions and most of the hydrogens have been omitted for clarity. Only one asymmetric

unit is shown. Selected bond distances (Å) and bond angles (deg): Ru(1a)-C(1a), 2.03(1);

Ru(1a)-N(3a), 2.195(7); Ru(1a)-N(4a), 2.156(8); Ru(1a)-C(14a), 2.215(9); C(1a)-Ru(1a)-N(3a),

91.9(3); N(3a)-Ru(1a)-N(4a), 90.9(4); C(1a)-Ru(1a)-N(3a), 81.3(3).


counteranions and most of the hydrogens have been omitted for clarity. Selected bond distances

(Å) and bond angles (deg): Ru(1)-P(1), 2.314(1); Ru(1)-N(1), 2.188(2); Ru(1)-N(2), 2.171(2);

Ru(1)-C(8), 2.207(3); P(1)-Ru(1)-N(1), 84.89(7); N(1)-Ru(1)-N(2), 87.35(9); P(1)-Ru(1)-N(2),

95.72(7).

914.3.5 The Transfer Hydrogenation of Acetophenone Catalyzed by Complexes 12, 13 and 14.

The tests of activity of the ruthenium(II) complex 13 as a catalyst for the transfer hydrogenation

of acetophenone in 2-propanol are listed in Table 4.1. It is not an active catalyst for the transfer

hydrogenation of acetophenone at room temperature (25°C) in the presence of potassium tert-

butoxide (KOtBu) and 2-propanol (Table 4.1, entry 1, catalyst to base to substrate ratio (C/B/S) =

1/8/200). At 75 °C, however, complex 13 catalyzed the hydrogenation of acetophenone to 1-

phenylethanol to 96% conversion in 3 h at the same C/B/S ratio (Table 4.1, entry 2, Figure 4.9).

The substrate to catalyst loading could be increased to 1200 to achieve 82% conversion in 3 h

and a maximum turnover frequency (TOF) of up to 880 h-1 (Table 4.1, entries 5 and 6).

Figure 4.9. Catalytic transfer hydrogenation of acetophenone to 1-phenylethanol in the presence

of 13, potassium tert-butoxide, and 2-propanol (6 mL) at 75°C (C/B/S = 1/8/200). The

conversions from two runs and an average of these are shown.

The nickel(II) complex 12, under the same conditions, showed no conversion of acetophenone

to 1-phenylethanol, even after 18 h of reaction (Table 4.1, entry 11). The system with simply the

dimer [Ru(p-cymene)Cl2]2 in basic 2-propanol gave a 91% conversion to 1-phenylethanol after 3

h with a higher TOF compared to that of complex 13 (Table 4.1, entry 14). However, the 1H

NMR spectrum of complex 13 in solution did not show any trace of [Ru(p-cymene)Cl2]2 nor

complex 12; thus the aforementioned catalytic activity is intrinsic to 13. Of note, ruthenium(II)

33. (a) Yigit, M.; Yigit, B.; Ozdemir, I.; Cetinkaya, E.; Cetinkaya, B., Appl. Organomet. Chem. 2006, 20, 322-327; (b) Fekete, M.; Joo, F., Collect. Czech. Chem. Commun. 2007, 72, 1037-1045.

92complexes bearing η6-arene ligands and N-heterocyclic carbene donors25e, 28b, 33 required

refluxing temperatures and long reaction times for full conversion of acetophenone to 1-

phenylethanol. Complex 13, on the other hand, gave more than a 90% conversion to 1-

phenylethanol in 1 h under refluxing temperature (Table 4.1, entry 9). When additional

acetophenone (C/S = 1/200) was added after 3 h to the 2-propanol reaction mixture (C/B/S =

1/8/200), the catalyst showed similar activity and reached an overall conversion to 1-

phenylethanol of 93% (Figure 4.10). The catalytic activity, therefore, must be due to the presence

of the same active species, but not any other decomposed products. This also suggested that the

active catalyst is not poisoned by the presence of 1-phenylethanol that is generated, nor

decomposed by exposure to the basic medium and reaction temperature.

Figure 4.10. Addition of acetophenone (200 mg, C/S = 1/200) after 180 min of transfer

hydrogenation of acetophenone in the presence of 13, potassium tert-butoxide, and 2-propanol (6

mL) at 75°C (C/B/S = 1/8/200).

The catalytic activity of complex 14 in the transfer hydrogenation of acetophenone was tested

using reaction conditions similar to those for the ruthenium(II) complex 13. The activated

complex catalyzed the transfer hydrogenation of acetophenone to 40% conversion to the product

alcohol in 18 h at 75°C (C/B/S = 1/8/200, Table 4.1, entry 12 ). This has lower activity in the

transfer hydrogenation of acetophenone in 2-propanol solution compared its ruthenium(II)

counterpart and analogous systems reported in the literature.27d, 34 The poor activity of complex 34. Faller, J. W.; Lavoie, A. R., Org. Lett. 2001, 3, 3703-3706.

9314 when activated in comparison to 13 might be attributed to the oxophilic nature of the metal

center to form stable osmium(II)-alkoxide complexes. Of note, the osmium(II) complex showed

no activity when it is not activated by KOtBu (Table 4.2, entry 13).

Table 4.1. The transfer hydrogenation of acetophenone to 1-phenylethanol in basic 2-propanol

catalyzed by complexes 12, 13 and 14.

Entry/Complex

C/B/Sa

ratioBase Temperature

/°CConversion (%/h)b TOF/h-1

1/13 1/8/200 KOtBu 25 0/1 0/2 0/3 02/13 1/8/200 KOtBu 75 87/1 94/2 96/3 2733/13 1/4/200 KOtBu 75 65/1 87/2 96/3 1564/13 1/16/200 KOtBu 75 62/1 85/2 95/3 1325/13 1/8/600 KOtBu 75 82/1 89/2 90/3 6746/13 1/8/1200 KOtBu 75 66/1 78/2 82/3 8837/13 1/8/200 NaOiPr 75 67/1 89/2 95/3 1518/13 1/8/200 KOH 75 71/1 88/2 94/3 1879/13 1/8/200 KOtBu 85 94/1 96/2 - 36010/13 1/0/200 none 75 0/1 0/2 0/3 011/12 1/8/200 KOtBu 75 0/1 0/2 0/3 012/14 1/8/200 KOtBu 75 13/1 22/2 40/18 -c

13/14 1/0/200 none 75 0/1 0/2 0/3 014/[Ru]d 1/8/200 KOtBu 75 81/1 88/2 91/3 412

a C/B/S: catalyst to base to substrate ratio. All reactions were carried out in 2-propanol (6 mL). b

Conversions were determined by GC and are reported as an average of two runs. c TOF not

measured. d [Ru] = [Ru(p-cymene)Cl2]2.

The effect of the amount of base present during catalysis was also investigated. It was found

that the optimum activity of complex 13 occurred with a C/B ratio of 1/8, although a higher or

lower C/B ratio gave similar conversions after 3 h, but with lower TOF values (Table 4.1, entries

2-4). The use of sodium isopropoxide and potassium hydroxide in the same C/B ratio also gave

similar conversions after 3 h, but with lower TOF compared to the use of KOtBu (Table 4.1,

entries 2, 7, and 8). In the absence of base, complex 13 was not active for the hydrogenation of

acetophenone (Table 4.1, entry 10). The use of potassium hydroxide is informative. In this case

the water byproduct did not affect the catalytic activity. Of note, Noyori and co-workers have

shown that the ruthenium(II) complex Ru(p-cymene){(S,S)-TsNCHPhCHPhNH2}Cl ((S,S)-

94TsNCHPhCHPhNH2 = (1S,2S)-N-p-toluenesulfonyl-1,2-diphenylethylenediamine) in the

presence of potassium hydroxide and 2-propanol catalyzed the transfer hydrogenation of

acetophenone to 1-phenylethanol in 97% ee and 98% yield at 28°C after 10 h (C/B/S =

1/2/200).26a, 26b The related active catalysts, the amido complex Ru(p-cymene){(S,S)-

TsNCHPhCHPhNH} and the hydride-amine complex RuH(p-cymene){(S,S)-

TsNCHPhCHPhNH2}, showed the same catalytic activity without the use of base.2b, 26b, 35 These

are referred to as bifunctional catalysts since both the metal and the amido ligand work together

in the formation of the active hydride-amine species from 2-propanol and the transfer of the a

Ru-H/N-H pair from the hydride-amine complex to the carbonyl group of the ketone.2b, 35

Table 4.2. The hydrogenation of acetophenone catalyzed by complex 15 in the presence of

KOtBu.a

O 15 cat.H2, KOtBu

25°C

HO H

Entry P(H2)/bar C/B/S ratio Conversion (%/min)b TOF/h-1 c

1 2 1/8/2515 16/60 99/120 31102 8 1/8/2515 30/20 98/30 103003d 8 1/8/11500 29/30 97/90 72404e 8 1/8/2515 46/4 98/10 176005f -/Ar 1/8/1200 53/30 82/120 1270

a Reactions were carried out in a 50 mL Parr hydrogenation reactor in THF (6 mL) at 25°C

unless otherwise stated; KOtBu was used as the base. b Conversions were determined by GC and

are reported as an average of two runs. c Determined from the slope of the linear portion of

[alcohol] vs. time plot. d No solvent was used. e 2-Propanol was used as solvent. f Conducted

under an argon environment and 2-propanol was used as solvent.

4.3.6 The H2-Hydrogenation of Ketones Catalyzed by Complexes 15 and 16. Complex 15,

when reacted with KOtBu in THF, is an efficient catalyst for the H2-hydrogenation of

acetophenone (Table 4.2). Full conversion to 1-phenylethanol is achieved within 30 min under 8

bar of H2 in THF at 25°C with a C/B/S ratio of 1/8/2515. On the other hand, full conversion is

achieved in 10 min under similar catalytic conditions when 2-propanol was used with a TOF of

17 600 h-1. Complex 15 also catalyzed the transfer hydrogenation of acetophenone in 2-propanol 35. (a) Ikariya, T.; Blacker, A. J., Acc. Chem. Res. 2007, 40, 1300-1308; (b) Kuwata, S.; Ikariya, T., Dalton

Trans. 2010, 39, 2984-2992.

95at 25°C, but with a smaller TOF value (Table 4.2, entry 5). By comparison, complex 16a is a

poor catalyst which when activated (C/B/S=1/8/200) produces a maximum conversion of 8% in

4 h under 25 bar of H2 in THF at 50°C. The related complex 16b catalyzed the hydrogenation of

acetophenone under 1 atm of H2 in 2-propanol at 50°C (Ru/KOH/substrate = 1/1/100) with 16%

conversion in 1 h.16 In terms of selectivity and broad substrate scope (vide infra), complex 15 is

superior to these and a few other ruthenium(II) complexes with NHC ligands that have been

reported to catalyze the H2-hydrogenation of ketones and aldehydes,25d, 36 and it is comparable to

or better than many P–NH2 systems of ruthenium(II).3b, 3c, 4, 5b, 37

Some results of the H2-hydrogenation of substituted acetophenones are listed in Table 4.3. In

general, TOF values decrease with increasing donor ability at the 4' position of the aryl group on

the ketone. On the other hand, an increase in substituent bulk on the acyl group gave variable

TOF values. Pinacolone is effectively hydrogenated but not 1R-(–)-fenchone (Table 4.4, entries

1–5).

Table 4.3. The hydrogenation of substituted acetophenones catalyzed by complex 15 in the

presence of KOtBu.a

O 15 cat.H2, KOtBu

25°C

RHO

RH

Entry R Conversion (%/min) TOF/h-1

1 2'-Chloro- 46/40 99/60 24002 3'-Chloro- 41/15 99/20 80503 4'-Chloro- 45/15 99/25 78004 4'-Bromo- 18/15 99/30 69705 4'-Methoxy- 42/15 99/25 5180

a Reactions were carried out in a 50 mL Parr hydrogenation reactor in THF (6 mL) at 8 bar of H2

pressure at 25°C. KOtBu was used as the base. The C/B/S ratio was 1/8/1500.

36. (a) Chantler, V. L.; Chatwin, S. L.; Jazzar, R. F. R.; Mahon, M. F.; Saker, O.; Whittlesey, M. K., Dalton Trans. 2008, 2603-2614; (b) Lee, J. P.; Ke, Z. F.; Ramirez, M. A.; Gunnoe, T. B.; Cundari, T. R.; Boyle, P. D.; Petersen, J. L., Organometallics 2009, 28, 1758-1775.37. Diaz-Valenzuela, M. B.; Phillips, S. D.; France, M. B.; Gunn, M. E.; Clarke, M. L., Chem. Eur. J. 2009, 15, 1227-1232.

96In the case of ketone hydrogenation, a sigmoidal type conversion curve was observed with a

variable induction period (10 - 30 min) depending on the ketone of interest (Figure 4.11). The

mercury test38 was employed in the hydrogenation of 4'-chloroacetophenone to test for the

possibility of catalysis by ruthenium nanoparticles. The catalytic activity was not perturbed

during the course of the reaction (Figure 4.12). Catalysis conducted in 2-propanol did not have

an induction period. We postulate that the product alcohol might auto-catalyze the heterolytic

splitting of dihydrogen by acting as a proton shuttle.1b, 16, 39

Figure 4.11. Catalytic H2-hydrogenation of 4'-bromoacetophenone to 1-(4'-bromophenyl)ethanol

(Table 4.3, entry 4) in the presence of catalyst 15, KOtBu, and THF (6 mL) in 8 bar of H2

pressure at 25°C (C/B/S = 1/8/1500).The concentrations of the product alcohol from two runs

and an average of these are shown.

4.3.7 The H2-Hydrogenation of Other Polar Bonds Catalyzed by Complex 15. The H2-

hydrogenation of other polar bonds catalyzed by complex 15 with base was also investigated.

Thus, benzaldehyde and N-(benzylidene)aniline were not hydrogenated, and N-(1-phenyl-

ethylidene)aniline was hydrogenated to its tertiary amine in 43% conversion within 2 h (Table

4.4, entries 6, 10 and 11). On the other hand, complex 15 catalyzed the hydrogenolysis of styrene

oxide in 2-propanol at 25°C with a TOF of 67 h-1 to produce phenylethanol with branched to

38. Jaska, C. A.; Manners, I., J. Am. Chem. Soc. 2004, 126, 9776-9785.39. (a) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q., J. Am Chem Soc. 2005, 127, 3100-3109; (b) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G., J. Am. Chem. Soc. 2005, 127, 15083-15090; (c) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R. H., Organometallics 2007, 26, 5987-5999.

97linear ratio of 89 : 11 (Table 4.4, entry 7). A similar branched to linear alcohol ratio was

observed when 16b was used as a catalyst, yet with a smaller TOF value (32 h-1).6a

The homogenous hydrogenation of esters is usually challenging. Most ruthenium(II) catalysts

require a high temperature and H2 pressure with low substrate loadings to achieve conversion to

the alcohol.5a, 5b, 40 Complex 15 catalyzed the hydrogenation of methyl benzoate to benzyl

alcohol and methanol at 25°C and 8 bar H2 with a TOF of 209 h-1, or at 50°C and 25 bar H2 with

a TOF of 838 h-1 and appreciable substrate loading (C/B = 1/1500) (Table 4.4, entries 8 and 9).

No other side products were observed. The catalyst trans-RuCl2(κ2(P,P)-PPh2CH2CH2NH2)2,

provides comparable activity but at higher temperature (100°C) and H2 pressure (50 bar).5a

Ruthenium(II) catalyst containing a pyridine-based41 and a bipyridine-based40d CNN pincer

ligand (C = N-heterocyclic carbene) has excellent activity to hydrogenate a variety of esters at

low H2 pressure (up to 5 bar) but at high temperature (up to 135°C).

Figure 4.12. Catalytic H2-hydrogenation of 4'-chloroacetophenone to 1-(4'-chlorophenyl)ethanol

in the presence of catalyst 15, KOtBu, and THF (6 mL) in 8 bar of H2 at 25°C (C/B/S =

1/14/2250). Mercury poisoning test was conducted by adding a drop of mercury to the reaction

mixture against a flow of hydrogen at 15 min.

40. (a) van Engelen, M. C.; Teunissen, H. T.; de Vries, J. G.; Elsevier, C. J., J. Mol. Catal. A: Chem. 2003, 206, 185-192; (b) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D., Angew. Chem. Int. Ed. 2006, 45, 1113-1115; (c) Takebayashi, S.; Bergens, S. H., Organometallics 2009, 28, 2349-2351; (d) Fogler, E.; Balaraman, E.; Ben-David, Y.; Leitus, G.; Shimon, L. J. W.; Milstein, D., Organometallics 2011, 30, 3826-3833.41. Sun, Y.; Koehler, C.; Tan, R.; Annibale, V. T.; Song, D., Chem. Commun. 2011, 47, 8349-8351.

98Table 4.4. The hydrogenation of organic molecules with polar bonds catalyzed by complex 15 in

the presence of KOtBu.a

OO O

O

H

O O

O

MeO N

h i j k

l m n

NO

g

o p

Entry Substrate Conversion (%/min) TOF/h-1

1 g 75/5 99/15 134002 h 49/60 99/120 11103 i 42/5 99/15 81004 j 58/5 99/15 104005 k 0/60 1/120 06 l 1/60 1/120 07b m 9/120 13/180e 678c n 10/120 23/180 2099c,d n 48/60 78/120 83810e o 0/60 0/120 011e p 28/60 43/120 247

a Unless otherwise stated, all reactions were carried out in a 50 mL Parr hydrogenation reactor in

THF (6 mL) at 8 bar of H2 pressure and 25°C. KOtBu was used as base. The C/B/S ratio was

1/8/1500. b 2-Propanol was used as solvent. Branched to linear alcohol ratio: 89 : 11. c Tridecane

was used as an internal standard for GC analysis. d Reaction was carried out at 25 bar of H2

pressure and 50°C. e Conversion determined by 1H NMR spectroscopy.

4.4 Conclusion

In summary, we have reported the facile synthesis of a primary amino-functionalized N-

heterocyclic carbene (C–NH2) complex by reduction under mild conditions of a nitrile-

functionalized imidazolium salt. The resulting nickel(II) complex 12 is an axially chiral square-

planar complex, and the use of Δ-TRISPHAT as a NMR chiral shift reagent is particularly useful

99to observe the diastereotopic ion pairs. A transmetalation reaction that moved the chelating C–

NH2 ligand from complex 12 to the [M(p-cymene)Cl]2 dimer (M = Ru, Os) and RuCp*(cod)Cl

afforded the first ruthenium(II) and osmium complexes 13 – 15 with such a C–NH2 ligand.

Complex 13 catalyzed the transfer hydrogenation of acetophenone in basic 2-propanol at 75°C in

3 h to give 1-phenylethanol with a TOF of up to 880 h-1. The osmium(II) analogue, complex 14,

was less active in the transfer hydrogenation of acetophenone in basic 2-propanol compared to its

ruthenium(II) counterpart. Complex 15, on the other hand, provides an active catalyst for the

hydrogenation of a variety of polar bonds under mild conditions using hydrogen gas in basic

medium.


4.5.1 Synthesis. All of the preparations and manipulations, except where otherwise stated, were

carried out under a nitrogen, argon, or hydrogen atmosphere using standard Schlenk-line and

glovebox techniques. Dry and oxygen-free solvents were always used unless otherwise stated.

Methanol was stirred over magnesium turnings and iodine chips overnight under an argon

atmosphere, refluxed for 2-3 h, and distilled prior to use. The synthesis of the imidazolium salt

1a was described in Chapter 2.12 The syntheses of [Ru(p-cymene)Cl2]2,42 [Os(p-cymene)Cl2]2,27a,

43 RuCp*(cod)Cl44 and 2-(diphenylphosphino)benzylamine (P–NH2)30 were reported in the

literature. All other reagents and solvents were purchased from commercial sources and were

used as received. Deuterated solvents were purchased from Cambridge Isotope Laboratories and

Sigma Aldrich and degassed and dried over activated molecular sieves prior to use. NMR spectra

were recorded on a Varian 400 spectrometer operating at 400 MHz for 1H, 100 MHz for 13C, 161

MHz for 31P and 376 MHz for 19F. The 1H and 13C{1H} NMR were measured relative to partially

deuterated solvent peaks but are reported relative to tetramethylsilane (TMS). All 19F chemical

shifts were measured relative to trichlorofluoromethane as an external reference. All 31P

chemical shifts were measured relative to 85% phosphoric acid as an external reference. All

infrared spectra were recorded on a Nicolet 550 Magna-IR spectrometer. All UV-vis spectra

were recorded on a Hewlett-Packard Agilent 8453 UV-vis spectrophotometer. The elemental

analysis was performed at the Department of Chemistry, University of Toronto, on a Perkin- 42. Bennett, M. A.; Smith, A. K., Dalton Trans. 1974, 233-241.

43. Cabeza, J. A.; Maitlis, P. M., Dalton Trans. 1985, 573-578.44. (a) Fagan, P. J.; Ward, M. D.; Calabrese, J. C., J. Am. Chem. Soc. 1989, 111, 1698-1719; (b) Fagan, P. J.; Mahoney, W. S.; Calabrese, J. C.; Williams, I. D., Organometallics 1990, 9, 1843-1852.

100Elmer 2400 CHN elemental analyzer. Samples were handled under argon where it was


diffractometer with Mo Kα radiation (λ = 0.71073 Å). The CCD data were integrated and scaled


Refinement was by full-matrix least-squares on F2 using all data.

4.5.2 Synthesis of Bis[1-(2-aminomethylphenyl)-3-methylimidazol-2-ylidene]nickel(II)

Hexafluorophosphate ([Ni(C–NH2)2](PF6)2, 12). A Schlenk flask was charged with anhydrous

nickel(II) chloride (239 mg, 1.8 mmol) and the imidazolium salt 1a (500 mg, 1.8 mmol). A warm

methanol solution (48 mL) was added to the solid mixture under an argon or a hydrogen

atmosphere, and the solution was stirred until all the imidazolium salt dissolved. A fresh, cold

methanolic solution (12 mL) of sodium borohydride (489 mg, 12.9 mmol, previously prepared

by dissolving sodium borohydride in methanol at 0°C) was added via a syringe and a needle

slowly to the orange slurry containing anhydrous nickel(II) chloride and the imidazolium salt at

-78°C, and vigorous effervescence occurred. The dark black slurry was stirred for 1 h at -78°C,

slowly warmed to room temperature, and stirred overnight. After the reaction had gone to

completion, the solvent was removed in vacuo. The residue was extracted with commercial grade

dichloromethane (20 mL) in air and filtered through a pad of Celite. If the filtrate was not clear,

water (2 mL) was added to the dichloromethane solution and filtered through a pad of Celite

again to remove all the black residue. The organic layer was then extracted with water (5 × 8

mL). The orange aqueous solution was filtered through a plug of cotton wool, and the clear

solution was added to a saturated aqueous solution (1 mL) of ammonium hexafluorophosphate

(363 mg, 2.2 mmol). The yellow-orange precipitate was then collected, rinsed with water (5 mL),

and dried in vacuo. Yield: 200 mg, 30%. Suitable crystals for X-ray diffraction studies were

obtained by slow diffusion of diethyl ether solution into a saturated solution of 12 in acetonitrile. 1H NMR (CD3CN, δ): 7.78 (dt, JHH = 1.19, 7.77 Hz, 5-CH of Ph, 1H), 7.75 (dd, JHH = 1.73, 7.77

Hz, 6-CH of Ph, 1H), 7.69 (dt, JHH = 1.73, 7.40 Hz, 4-CH of Ph, 1H), 7.62 (dd, JHH = 1.19, 7.40

Hz, 3-CH of Ph, 1H), 7.36 (d, JHH = 1.79 Hz, 5-CH of imid., 1H), 7.21 (d, JHH = 1.79, 4-CH of

imid., 1H), 3.56 (dd, JHH = 3.89, 12.13 Hz, CH2, 1H), 3.44 (s, CH3, 3H), 2.80 (m, br, NH2, 2H),

2.53 (dt, JHH = 4.37, 12.22 Hz, CH2, 1H). 19F NMR (CD3CN, δ): -73.3 (d, JPF = 706 Hz). 13C{1H}

NMR (CD3CN, δ): 159.0 (Ni–C), 139.1 (CPh), 133.9 (CPh), 133.0 (CPh), 131.6 (CPh), 130.5(CPh),

126.5 (Cimid.), 126.2 (CPh), 125.2 (Cimid.), 44.1 (CH2), 37.8 (CH3). IR (KBr, cm-1): 3347, 3275

(ν(NH) stretch). UV-vis (acetonitrile; λmax (nm), ε (M-1cm-1)): 380, 364. MS (ESI,

101methanol/water; m/z): 431.1 ([M – H]+). Anal. Calcd for C22H26F12N6NiP2: C, 36.54; H, 3.62; N,

11.62. Found: C, 36.78; H, 3.71; N, 12.69.

4.5.3 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene]chloro(η6-p-

cymene)ruthenium(II) Hexafluorophosphate ([Ru(p-cymene)(C–NH2)Cl]PF6, 13). A

Schlenk flask was charged with 12 (135 mg, 0.19 mmol) and [Ru(p-cymene)Cl2]2 dimer (114

mg, 0.19 mmol). Dry acetonitrile (16 mL) was added to the reaction mixture, and it was refluxed

under an argon atmosphere for 2.5 h to give a green solution. The solvent was then evacuated.

The residue was extracted with tetrahydrofuran or dichloromethane (8 mL) and filtered through a

pad of Celite. The volume of solvent was reduced (2 mL), and addition of diethyl ether (10 mL)

to the tetrahydrofuran or dichloromethane solution yielded a yellow precipitate, which was

collected and dried in vacuo. Yield: 135 mg, 60%. Suitable crystals for an X-ray diffraction

studies were obtained by slow evaporation of the filtrate solution in tetrahydrofuran and diethyl

ether under a nitrogen atmosphere. 1H NMR(CD2Cl2, δ): 7.69 (m, 3-CH of Ph, 1H), 7.60 (m, 4-

CH and 5-CH of Ph, 2H), 7.48 (m, 6-CH of Ph, 1H), 7.37 (d, JHH = 1.92 Hz, 5-CH of imid., 1H),

7.35 (d, JHH = 1.92 Hz, 4-CH of imid., 1H), 5.50 (d, JHH = 5.80 Hz, 2-Ar-CH of p-cymene, 1H),

5.29 (d, JHH = 5.74 Hz, 6-Ar-CH of p-cymene, 1H), 5.15 (d, JHH = 5.74 Hz, 5-Ar-CH of p-

cymene, 1H), 5.12 (m, br, NH2, 1H), 4.74 (d, JHH = 5.80 Hz, 3-Ar-CH of p-cymene, 1H), 4.07 (s,

CH3, 3H), 3.96 (m, CH2, 1H), 3.68 (m, br, NH2, 1H), 2.86 (t, JHH = 11.19 Hz, CH2, 1H), 2.55

(sept, JHH = 7.01 Hz, CH of (CH3)2CH of p-cymene, 1H), 1.67 (s, CH3 of p-cymene, 3H), 1.13

(dd, JHH = 1.29, 7.01 Hz, CH3 of (CH3)2CH of p-cymene, 1H). 19F NMR (CD2Cl2, δ): -72.3 (d,

JPF = 712 Hz). 13C{1H} NMR (CD2Cl2, δ): 175.1 (Ru–C), 138.8 (CPh), 132.8 (CPh), 131.6 (CPh),

130.4 (CPh), 130.0 (CPh), 125.9 (Cimid.), 125.6 (Cimid.), 124.5 (CPh), 111.6 (CAr-p-cymene), 101.1 (CAr-

p-cymene), 86.6 (CAr-p-cymene), 85.4 (CAr-p-cymene), 84.3 (CAr-p-cymene), 82.2 (CAr-p-cymene), 46.6 (CH2),

39.8 (CH3), 31.1 (CH of (CH3)2CH of p-cymene), 23.6 (CH3 of p-cymene), 21.0, (CH3 of

(CH3)2CH of p-cymene), 18.7 (CH3 of (CH3)2CH of p-cymene). IR(KBr, cm-1): 3326, 3279

(ν(NH) stretch). UV-vis (acetonitrile; λmax (nm), ε (M-1 cm-1)): 391, 360. MS (ESI,

methanol/water; m/z): 458.1 ([M]+). HRMS (ESI, methanol/water; m/z): calcd for

C21H27N3ClRu+ ([M]+) 458.0931, found 458.0915. Several attempts at elemental analyses failed

to give an acceptable carbon content, while hydrogen and nitrogen content are in the acceptable

range. Typical results: Anal. Calcd for C21H27F6N3ClPRu: C, 41.83; H, 4.51; N, 6.97. Found: C,

38.22; H, 4.41; N, 6.47.

1024.5.4 Synthesis of [1-(2-(Aminomethyl)phenyl)-3-methylimidazol-2-ylidene]chloro(η6-p-

cymene)osmium(II) Hexafluorophosphate ([Os(p-cymene)(C–NH2)Cl]PF6, 14). A Schlenk

flask was charged with 12 (46 mg, 0.064 mmol) and the [Os(p-cymene)Cl2]2 dimer (50 mg,

0.063 mmol). Dry acetonitrile (8 mL) was added to the reaction mixture, and it was refluxed

under an argon atmosphere for 2.5 h to give a green solution. The solvent was then evacuated.

The residue was extracted with THF (4 mL) and filtered through a pad of Celite. The volume of

solvent was reduced (2 mL), and addition of diethyl ether (12 mL) to the THF solution yielded a

pale yellow precipitate which was collected and dried in vacuo. Yield: 81 mg, 93%. Crystals

suitable for an X-ray diffraction study were obtained by slow diffusion of diethyl ether into a

saturated solution of 14 in a 1/1 acetonitrile/methanol mixture under a nitrogen atmosphere. 1H

NMR(CD2Cl2, δ): 7.70 (m, 3-CH of Ph, 1H), 7.59 (m, 4-CH and 5-CH of Ph, 2H), 7.41 (m, 6-

CH of Ph, 1H), 7.24 (d, JHH = 1.95 Hz, 5-CH of imid, 1H), 7.22 (d, JHH = 1.95, 4-CH of imid,

1H), 5.88 (m, br, NH2, 2H), 5.58 (d, JHH = 5.44 Hz, 2-Ar-CH of p-cymene, 1H), 5.51 (d, JHH =

5.51 Hz, 6-Ar-CH of p-cymene, 1H), 5.30 (d, JHH = 5.51 Hz, 5-Ar-CH of p-cymene, 1H), 4.98

(d, JHH = 5.44 Hz, 3-Ar-CH of p-cymene, 1H), 4.21 (m, CH2, 1H), 4.03 (s, CH3, 3H), 3.15 (dt,

JHH = 2.54, 12.28 Hz, CH2, 1H), 2.48 (sept, JHH = 6.88 Hz, CH of (CH3)2CH of p-cymene, 1H),

1.77 (s, CH3 of p-cymene, 3H), 1.14 (d, JHH = 6.91 Hz, CH3 of (CH3)2CH of p-cymene, 3H), 1.07

(d, JHH = 6.91 Hz, CH3 of (CH3)2CH of p-cymene, 3H). 19F NMR (CD2Cl2, δ): -72.0 (d, JPF = 712

Hz). 13C{1H} NMR (CD2Cl2, δ): 159.4 (Os–C), 138.9 (CPh), 132.8 (CPh), 131.0 (CPh), 130.5

(CPh), 130.0 (CPh), 125.6 (Cimid.), 124.9 (CPh), 123.5 (Cimid.), 102.8 (CAr-p-cymene), 92.5 (CAr-p-

cymene), 78.2 (CAr-p-cymene),76.9 (CAr-p-cymene), 75.6 (CAr-p-cymene), 73.1 (CAr-p-cymene), 47.7 (CH2), 39.8

(CH3), 31.0 (CH of (CH3)2CH of p-cymene), 23.9 (CH3 of p-cymene), 21.2, (CH3 of (CH3)2CH

of p-cymene), 18.7 (CH3 of (CH3)2CH of p-cymene). MS (ESI, methanol/water; m/z): 548.2 ([M]+). HRMS (ESI, methanol/water; m/z): calcd for C21H27N3ClOs+ ([M]+) 548.1502, found

548.1463. Anal. Calcd for C21H27ClF6N3OsP: C, 36.44; H, 3.93; N, 6.07. Found: C, 37.04; H,

3.44; N, 5.51.

4.5.5 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene](η5-pentamethyl-

cyclopentadienyl)(pyridine)ruthenium(II) Hexafluorophosphate ([RuCp*(C–NH2)(py)]PF6,

15). A Schlenk flask was charged with 12 (73 mg, 0.10 mmol) and RuCp*(cod)Cl (58 mg, 0.15

mmol). Dry acetonitrile (10 mL) was added to the reaction mixture, and it was refluxed under an

argon atmosphere for 2.5 h. The colour of the solution turned from yellow to cloudy yellow and

then to deep green. The solvent was evaporated under reduced pressure, and the residue was

103extracted with oxygen-free tetrahydrofuran (4 mL) and filtered through a pad of Celite under a

nitrogen atmosphere. To the yellow-brown solution was added pyridine (1 mL), whereupon the

colour of the solution turned into deep orange-red. The solution was evaporated under reduced

pressure, and the solid residue was extracted with ice-cold acetone (2 mL) and filtered through a

pad of Celite. Addition of diethyl ether (15 mL) to the acetone solution and slow cooling of the

solution at -25°C afforded orange-red needles, which were collected on a glass frit, washed with

diethyl ether (1 mL) and dried in vacuo. Yield: 63 mg, 64%. Suitable crystals for an X-ray

diffraction study were obtained by slow diffusion of diethyl ether into a saturated solution of 15

in acetone under a nitrogen atmosphere. 1H NMR (acetone-d6, 233K, δ): 8.49 (m, 4-CH of py,

1H), 7.88 (m, 2-CH of py, 2H), 7.77 (m, 3-CH of Ph, 1H), 7.67 (d, JHH = 1.99 Hz, 5-CH of

imid.,1H), 7.63 (m, 4-CH and 5-CH of Ph, 2H), 7.60 (d, JHH = 1.99 Hz, 4-CH of imid., 1H), 7.49

(m, 6-CH of Ph, 1H), 7.42 (m, 3-CH of py, 2H), 4.23 (t, JHH = 13.37 Hz, CH2, 1H), 3.48 (s, CH3,

3H), 3.30 (t, JHH = 9.22 Hz, CH2, 1H), 2.83 (m, br, NH2, 1H), 2.59 (m, br, NH2, 1H), 1.23 (s,

CH3 of Cp*, 15H). 19F NMR (acetone-d6, 233K, δ): -72.0 (d, JPF = 708 Hz). 13C{1H} NMR

(acetone-d6, 233K, δ): 198.0 (Ru–C), 156.0 (Cpy), 141.8 (Cpy), 136.3 (CPh), 132.9 (CPh), 132.5

(CPh), 130.0 (CPh), 128.3 (CPh), 127.1 (CPh), 126.6 (Cpy), 124.8 (Cimid.), 124.3 (Cimid.), 80.7 (CAr-

Cp*), 48.7 (CH2), 37.6 (CH3), 9.6 (CH3 of Cp*). MS (ESI, methanol/water; m/z): 456.1 ([M – py +

CH3OH]+), 424.1 ([M – py]+). Anal. Calcd for C26H33F6N4PRu: C, 48.22; H, 5.14; N, 8.65.

Found: C, 47.73; H, 4.20; N, 9.25.

4.5.6 Synthesis of [2-(Diphenylphosphino)benzylamine](η5-pentamethylcyclopentadienyl)-

(pyridine)ruthenium(II) Hexafluorophosphate ([RuCp*(P–NH2)(py)]PF6, 16a). A

scintillation vial with a threaded screw cap was charged with RuCp*(cod)Cl (40 mg, 0.11 mmol)

in dry dichloromethane (3 mL) under a nitrogen atmosphere. A solution of 2-(diphenyl-

phosphino)benzylamine (32 mg, 0.10 mmol) in dry dichloromethane (3 mL) was added to the

aforementioned yellow solution and stirred for 1 h at room temperature (25°C), whereupon the

reaction mixture turned into orange in colour. Silver hexafluorophosphate (27 mg, 0.11 mmol) in

dry acetonitrile (1 mL) was added to the reaction mixture, and a yellow-brown suspension was

obtained. After stirring the reaction mixture for 0.5 h, it was filtered through a pad of Celite

under a nitrogen atmosphere. To the yellow solution was added pyridine (1 mL), and the colour

of the solution turned into deep orange-yellow. Addition of pentane (15 mL) yielded an orange-

yellow precipitate, which was washed with pentane (3 mL) and dried in vacuo. Alternatively, the

crude product can be recrystallized with acetone and pentane or acetone and diethyl ether

104mixtures at -25°C to afford an orange-yellow solid. Yield: 53 mg, 67%. Suitable crystals for an

X-ray diffraction study were obtained by slow diffusion of diethyl ether into a saturated of 16a in

acetone under a nitrogen atmosphere. 1H NMR (CD2Cl2, 233K, δ): 7.76 (d, JHH = 5.20 Hz, 2-CH

of py, 2H), 7.56 (m, 6-CH of Ph, 1H), 7.47 (m, 5-CH of Ph, 1H), 7.45 (m, 4-CH of py, 1H), 7.42

(m, Ar-CH of PPh2, 10H), 7.19 (t, JHH = 8.32 Hz, 4-CH of Ph, 1H), 7.07 (dd, JHH = 7.44, 7.37

Hz, 3-CH of Ph, 1H), 6.93 (t, JHH = 7.40 Hz, 3-CH of py, 1H), 3.91 (m, CH2, 1H), 3.67 (m, CH2,

1H), 3.54 (m, br, NH2, 1H), 3.32 (m, br, NH2, 1H), 1.21 (s, CH3 of Cp*, 15H). 19F NMR

(CD2Cl2, 233K, δ): -72.4 (d, JPF = 712 Hz). 31P{1H} NMR (CD2Cl2, 233K, δ): 44.7 (s), -144.6

(sept, JPF = 709 Hz). 13C{1H} NMR (CD2Cl2, 233K, δ): 154.7 (Cpy), 136.0 (Cpy), 134.9 (CPh),

132.9 (t, JCP = 11.61 Hz, CPh), 130.4 (d, JCP = 8.64 Hz, CPh), 130.0 (CPh), 129.6 (d, JCP = 17.86

Hz, CPh), 128.7 (d, JCP = 9.05 Hz, CPh), 128.3 (m, CPPh), 124.8 (Cpy), 84.0 (CAr-Cp*), 46.6 (CH2),

9.0 (CH3 of Cp*). MS (ESI, methanol/water; m/z): 528.1 ([M – py]+). Anal. Calcd for

C34H38F6N2P2Ru: C, 54.33; H, 5.10; N, 3.73. Found: C, 54.00; H, 5.30; N, 3.75.

4.5.7 Catalysis. 2-Propanol that was used for all of the transfer hydrogenation runs was stirred

over magnesium turnings and iodine chips overnight under an argon atmosphere, refluxed for 2-3

h, and distilled prior to use. Oxygen-free tetrahydrofuran that was used for all of the catalytic

runs for H2-hydrogenation was stirred over sodium for 2-3 days under argon, and freshly distilled

from sodium benzophenone ketyl prior to use. Acetophenone was vacuum distilled over

phosphorus pentoxide (P2O5) and stored under nitrogen prior to use. All of the other substrates

were vacuum distilled, dried over activated molecular sieves, and stored under nitrogen prior to

use. All of the H2-hydrogenation reactions were performed at constant pressures using a stainless

steel 50 mL Parr hydrogenation reactor. The temperature was maintained at 25°C using a

constant-temperature water bath. The reactor was flushed several times with hydrogen gas at 2-4

bar prior to the addition of catalyst/substrate and base solutions.

A Perkin-Elmer Clarus 400 chromatograph equipped with a chiral column (CP chirasil-Dex

CB 25 m × 2.5 mm) with an auto-sampling capability was used for gas chromatography (GC)

analyses. Hydrogen was used as a mobile phase at a column pressure of 5 psi with a split flow

rate of 50 mL/min. The injector temperature was 250°C and the FID temperature was 275°C.

The oven temperatures and the retention times (tR, tp, /min) for all of the substrates and alcohol

products are given in the Appendix. All of the conversions are reported as an average of two GC

runs. The reported conversions were reproducible.

1054.5.8 General Procedure for Transfer Hydrogenation Studies. A solution of acetophenone

(200 mg, 1.7 mmol) in 2-propanol (6 mL) was added via a syringe and needle to a Schlenk flask

charged with a mixture of 13 (5 mg, 8.3 µmol) and potassium tert-butoxide (7 mg, 0.062 mmol)

at 75°C under an argon atmosphere. The solution became homogeneous upon stirring. Samples

were taken from the reaction mixture periodically by a syringe and needle and were quenched by

exposure to air. All samples for GC analyses were diluted to a total volume of approximately

0.75 mL using oxygenated 2-propanol.

4.5.9 General Procedure for H2-Hydrogenation Studies. In a typical run (Table 4.3, Entry 4),

the catalyst 15 (3 mg, 4.6 µmol) and 4'-bromoacetophenone (1.383 g, 6.9 mmol), and potassium

tert-butoxide (4 mg, 0.036 mmol) were dissolved in tetrahydrofuran (4 mL and 2 mL,

respectively) under a nitrogen atmosphere. The catalyst/substrate and base solutions were taken

up by means of two separate syringes and needles in a glovebox. The needles were stoppered and

the syringes were taken to the reactor. The solutions were then injected into the reactor against a

flow of hydrogen gas. The hydrogen gas was adjusted to the desired pressure. Small aliquots of

the reaction mixture were quickly withdrawn with a syringe and needle under a flow of hydrogen

at timed intervals by venting the Parr reactor at reduced pressure. Alternatively, small aliquots of

the reaction mixture were sampled from a stainless steel sampling dip tube attached to a

modified Parr reactor. The dip tube was 30 cm in length with an inner diameter of 0.01 in., and a

swing valve was attached to the end of the sampling tube. Other technical details were reported

elsewhere.45 Two small aliquots of samples were thereby withdrawn quickly at timed intervals

by opening the swing valve, and the first two aliquots were discarded. All samples for GC

analyses were diluted to a total volume of approximately 0.75 mL using oxygenated THF.

45. Zimmer-De Iuliis, M.; Morris, R. H., J. Am. Chem. Soc. 2009, 131, 11263-1126

106Chapter 5: Mechanistic Investigation of the Hydrogenation of

Ketones Catalyzed by a Ruthenium(II) Complex Featuring an N-

Heterocyclic Carbene with a Tethered Primary Amine Donor:

Evidence for an Inner Sphere Mechanism

5.1 Abstract

The complex [Ru(p-cymene)(C–NH2)Cl]PF6 (13) catalyzes the H2-hydrogenation of ketones

in basic THF under 25 bar of H2 at 50°C with a turnover frequency (TOF) of up to 461 h-1 and a

maximum conversion of 99%. When the substrate is acetophenone, the TOF decreases

significantly as the catalyst to substrate ratio is increased. The rate law is then determined to be

rate = kH[Ru]tot[H2]/(1 + Keq[ketone]), and [13] is equal to [Ru]tot if catalyst decomposition does

not occur. This is consistent with the heterolytic splitting of dihydrogen at the active ruthenium

species as the rate-determining step. In competition with this reaction is the reversible addition of

acetophenone to the active species to give an enolate complex. The transfer to the ketone of a

hydride and proton equivalent that are produced in the heterolytic splitting reaction yields the

product in a fast, low activation barrier step. The kinetic isotope effect was measured using D2

gas and acetophenone-d3, and this gave values (kH/kD) of 1.33 ± 0.15 and 1.29 ± 0.15,

respectively. The ruthenium hydride complex [Ru(p-cymene)(C–NH2)H]PF6 (17) was prepared,

as this was postulated to be a crucial intermediate in the outer-sphere bifunctional mechanism.

This is inactive under catalytic conditions unless it is activated by a base. DFT computations

suggest that the energy barriers for the addition of dihydrogen, heterolytic splitting of

dihydrogen, and concerted transfer of H+/H- to the ketone for the outer-sphere mechanism would

be respectively 18.0, 0.2, and 33.5 kcal/mol uphill at 298 K and 1 atm. On the other hand, the

energy barriers for an inner-sphere mechanism involving the decoordination of the amine group

of the NHC ligand, the heterolytic splitting of dihydrogen across a Ru–O(alkoxide) bond, and

hydride migration to the coordinated ketone, are respectively 15.5, 17.5, and 15.6 kcal/mol uphill

at 298 K and 1 atm. This is more consistent with the experimental observation that the

heterolytic splitting of dihydrogen is the turnover-limiting step. This was confirmed by showing

*Reproduced in part with permission from O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2011, 30, 1236-1252. Copyright 2011 American Chemical Society.

107that an analogous complex with a tethered tertiary amine group, [Ru(p-cymene)(C–NMe2)Cl]

PF6⋅1.5 DMSO (18), has comparable activity for the H2-hydrogenation of acetophenone.

5.2 Introduction

The hydrogenation of polar bonds using molecular hydrogen has remained by far the most

efficient process in terms of atom economy.1 However, dihydrogen is inert to reaction with most

organic substrates of interest, and so it must be activated by a transition metal complex,2 forming

metal hydride complexes, or more recently by main-group compounds such as frustrated Lewis

pairs.3 Bifunctional catalysis,4 which was originally proposed by Noyori and co-workers in the

pioneering work in the hydrogenation of polar bonds using the catalyst RuH(η6-p-cymene)((S,S)-

Tsdpen) (Tsdpen = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine)5 and, more generally,

late transition metal catalysts containing M–H and N–H groups6 have superior activities in the

selective reduction of polar bonds to produce valuable alcohols and amines. Several studies, both

theoretical7 and experimental,8 including the study of kinetic isotope effects,9 have been

conducted to understand the mechanism of action using the “NH effect” and the bifunctional

nature of the true form of catalytically active species. The presence of the N–H group and its

relationship to the outer-sphere bifunctional10 and inner-sphere mechanisms11 have also been

studied by many research groups.

1. (a) de Vries, J. G.; Elsevier, C. J., Eds. The Handbook of Homogeneous Hydrogenation; Wiley-VCH: Weinheim, Germany, 2004; Vols 1-3; (b) Ito, M.; Ikariya, T., Chem. Commun. 2007, 5134-5142; (c) Kubas, G. J., Chem. Rev. 2007, 107, 4152-4205.2. (a) Jessop, P. G.; Morris, R. H., Coord. Chem. Rev. 1992, 121, 155-284; (b) Morris, R. H., Can. J. Chem. 1996, 74, 1907-1915; (c) Rosales, M., Coord. Chem. Rev. 2000, 196, 249-280; (d) DuBois, M. R.; DuBois, D. L., Chem. Soc. Rev. 2009, 38, 62-72; (e) Gloaguen, F.; Rauchfuss, T. B., Chem. Soc. Rev. 2009, 38, 100-108.3. Stephan, D. W.; Erker, G., Angew. Chem. Int. Ed. 2010, 49, 46-76.4. (a) Muniz, K., Angew. Chem. Int. Ed. 2005, 44, 6622-6627; (b) Samec, J. S. M.; Bäckvall, J. E.; Andersson, P. G.; Brandt, P., Chem. Soc. Rev. 2006, 35, 237-248; (c) Ikariya, T.; Murata, K.; Noyori, R., Org. Biomol. Chem. 2006, 4, 393-406; (d) Grützmacher, H., Angew. Chem. Int. Ed. 2008, 47, 1814-1818; (e) Ito, M.; Ikariya, T., J. Synth. Org. Chem. Jpn. 2008, 66, 1042-1048; (f) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J., Chem. Rev. 2010, 110, 2294-2312; (g) Kuwata, S.; Ikariya, T., Dalton Trans. 2010, 39, 2984-2992; (h) Grotjahn, D. B., Top. Catal. 2010, 53, 1009-1014.5. Haack, K. J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R., Angew. Chem. Int. Ed. 1997, 36, 285-288.6. (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S., J. Org. Chem. 2001, 66, 7931-7944; (b) Clapham, S. E.; Hadzovic, A.; Morris, R. H., Coord. Chem. Rev. 2004, 248, 2201-2237.7. (a) Alonso, D. A.; Brandt, P.; Nordin, S. J. M.; Andersson, P. G., J. Am Chem Soc. 1999, 121, 9580-9588; (b) Yamakawa, M.; Ito, H.; Noyori, R., J. Am. Chem. Soc. 2000, 122, 1466-1478; (c) Handgraaf, J. W.; Reek, J. N. H.; Meijer, E. J., Organometallics 2003, 22, 3150-3157; (d) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G., J. Am. Chem. Soc. 2005, 127, 15083-15090; (e) Handgraaf, J. W.; Meijer, E. J., J. Am. Chem. Soc. 2007, 129, 3099-3103; (f) Di Tommaso, D.; French, S. A.; Catlow, C. R. A., J. Mol. Struct. (THEOCHEM) 2007, 812, 39-49; (g) Puchta, R.; Dahlenburg, L.; Clark, T., Chem. Eur. J. 2008, 14, 8898-8903; (h) Zhang, H. H.; Chen, D. Z.; Zhang, Y. H.; Zhang, G. Q.; Liu, J. B., Dalton Trans. 2010, 39, 1972-1978; (i) Chen, Z.; Chen, Y.; Tang, Y. H.; Lei, M., Dalton Trans. 2010, 39, 2036-2043; (j) Lei, M.; Zhang, W. C.; Chen, Y.; Tang, Y. H., Organometallics 2010, 29, 543-548.

108The many catalyst systems that were studied by our research group12 which undergo efficient

H2-hydrogenation of ketones and imines, including those of trans-Ru(H)2((R)-BINAP)(tmen),

(OC-6-22)-Ru(H)2(PPh3)2(tmen) (tmen = 2,3-dimethylbutane-2,3-diamine), and trans-Ru-

(H)2(κ4(P,N,N,P)-P2(NH)2)12d, 13 (P2(NH)2 = tetradentate diphosphinediamine ligand), were found

to have the heterolytic splitting of the coordinated η2-H2 ligand on the active species as the rate-

determining step from various mechanistic and computational studies.12c-g These are active

catalysts, without prior activation with base, and catalyze efficiently the reduction of ketones by

H2 under mild conditions.12b-f The energy barrier calculated for the model complex (OC-6-22)-

Ru(H)2(PH3)2(en) (en = ethylenediamine) was found to be higher in the heterolytic splitting of H2

compared to the concerted transfer of H+/H- to the ketone in a six-membered-ring transition state. 6, 7a-g, 7j The corresponding coordinatively unsaturated complexes containing a ruthenium-amido

bond were isolated, and these were also found to activate dihydrogen to give the trans-dihydride

complexes.12a, 12c-f For the system trans-Ru(H)2(diamine)((R)-BINAP), Bergens and co-workers

suggested a ruthenium(II) alkoxide complex was indeed formed prior to the formation of such

amido complexes.8b, 14

Not much work has been devoted to study the mechanism of action of catalysts containing

phosphine-amine ligands (P–NH2).15 The ruthenium catalysts containing these ligands effect not

only the reduction of ketones15c, 15f but also the hydrogenation of a broad range of substrates,

including imines,15d esters,16 epoxides,15a and other polar bonds.17 All these may utilize the same

bifunctional mechanism involving the action of the M–H and N–H groups. The notion of

replacing the phosphine with an N-heterocyclic carbene (NHC) donor, in particular, a donor-

functionalized NHC, is therefore attractive to achieve the goal of greener chemistry.18 We have

previously reported that the transfer hydrogenation catalyst [Ru(p-cymene)(C–NH2)Cl]PF6 (13,

8. (a) Maire, P.; Buttner, T.; Breher, F.; Le Floch, P.; Grützmacher, H., Angew. Chem. Int. Ed. 2005, 44, 6318-6323; (b) Hamilton, R. J.; Leong, C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H., J. Am. Chem. Soc. 2005, 127, 4152-4153; (c) Sandoval, C. A.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Noyori, R., Chem.-Asian J. 2006, 1, 102-110; (d) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori, R., J. Am. Chem. Soc. 2006, 128, 8724-8725; (e) Friedrich, A.; Drees, M.; auf der Gunne, J. S.; Schneider, S., J. Am. Chem. Soc. 2009, 131, 17552-17553; (f) Cheung, F. K.; Clarke, A. J.; Clarkson, G. J.; Fox, D. J.; Graham, M. A.; Lin, C. X.; Criville, A. L.; Wills, M., Dalton Trans. 2010, 39, 1395-1402.9. (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R., J. Am. Chem. Soc. 2003, 125, 13490-13503; (b) Kass, M.; Friedrich, A.; Drees, M.; Schneider, S., Angew. Chem. Int. Ed. 2009, 48, 905-907; (c) Zimmer-De Iuliis, M.; Morris, R. H., J. Am. Chem. Soc. 2009, 131, 11263-11269.10. (a) Noyori, R.; Ohkuma, T., Angew. Chem. Int. Ed. 2001, 40, 40-73; (b) Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T., Organometallics 2001, 20, 379-381; (c) Ma, G. B.; McDonald, R.; Ferguson, M.; Cavell, R. G.; Patrick, B. O.; James, B. R.; Hu, T. Q., Organometallics 2007, 26, 846-854; (d) Baratta, W.; Ballico, M.; Esposito, G.; Rigo, P., Chem. Eur. J. 2008, 14, 5588-5595; (e) Sandoval, C. A.; Shi, Q. X.; Liu, S. S.; Noyori, R., Chem. Asian J. 2009, 4, 1221-1224; (f) Soni, R.; Cheung, F. K.; Clarkson, G. C.; Martins, J. E. D.; Graham, M. A.; Wills, M., Org. Biomol. Chem. 2011, 9, 3290-3294.

109see Chapter 4) is effective for the hydrogenation of acetophenone to 1-phenylethanol in basic 2-

propanol at 75°C. This system reached a maximum conversion of 96% and a turnover frequency

(TOF) of 880 h-1 (Figure 5.1).19 Here we present our study toward its H2-hydrogenation activity

in the reduction of ketones and a detailed mechanistic investigation, including kinetic studies and

theoretical computations that were performed to study the possibility of the cooperative nature of

the ligand and the metal center in this new class of ligand system.20

Figure 5.1. Transfer hydrogenation of acetophenone catalyzed by complex 13 in basic 2-

propanol.

11. (a) Standfest-Hauser, C.; Slugovc, C.; Mereiter, K.; Schmid, R.; Kirchner, K.; Xiao, L.; Weissensteiner, W., Dalton Trans. 2001, 2989-2995; (b) Leong, C. G.; Akotsi, O. M.; Ferguson, M. J.; Bergens, S. H., Chem. Commun. 2003, 750-751; (c) Lundgren, R. J.; Rankin, M. A.; McDonald, R.; Schatte, G.; Stradiotto, M., Angew. Chem. Int. Ed. 2007, 46, 4732-4735; (d) Phillips, S. D.; Fuentes, J. A.; Clarke, M. L., Chem. Eur. J. 2010, 16, 8002-8005.12. (a) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2001, 123, 7473-7474; (b) Abdur-Rashid, K.; Lough, A. J.; Morris, R. H., Organometallics 2001, 20, 1047-1049; (c) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2002, 124, 15104-15118; (d) Rautenstrauch, V.; Hoang-Cong, X.; Churlaud, R.; Abdur-Rashid, K.; Morris, R. H., Chem. Eur. J. 2003, 9, 4954-4967; (e) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2005, 127, 1870-1882; (f) Clapham, S. E.; Morris, R. H., Organometallics 2005, 24, 479-481; (g) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R. H., Organometallics 2007, 26, 5987-5999.13. (a) Li, T.; Churlaud, R.; Lough, A. J.; Abdur-Rashid, K.; Morris, R. H., Organometallics 2004, 23, 6239-6247; (b) Li, T.; Bergner, I.; Haque, F. N.; Iuliis, M. Z.-D.; Song, D.; Morris, R. H., Organometallics 2007, 26, 5940-5949.14. (a) Hamilton, R. J.; Bergens, S. H., J. Am. Chem. Soc. 2008, 130, 11979-11987; (b) Takebayashi, S.; Dabral, N.; Miskolzie, M.; Bergens, S. H., J. Am Chem Soc. 2011, 133, 9666-9669.15. (a) Ito, M.; Hirakawa, M.; Osaku, A.; Ikariya, T., Organometallics 2003, 22, 4190-4192; (b) Dahlenburg, L.; Gotz, R., Eur. J. Inorg. Chem. 2004, 888-905; (c) Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529; (d) Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579; (e) Blaquiere, N.; Diallo-Garcia, S.; Gorelsky, S. I.; Black, D. A.; Fagnou, K., J. Am. Chem. Soc. 2008, 130, 14034-14035; (f) Jia, W. L.; Chen, X. H.; Guo, R. W.; Sui-Seng, C.; Amoroso, D.; Lough, A. J.; Abdur-Rashid, K., Dalton Trans. 2009, 8301-8307.16. (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P., Angew. Chem. Int. Ed. 2007, 46, 7473-7476; (b) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saito, T., Adv. Synth. Catal. 2010, 352, 92-96.17. (a) Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T., J. Am. Chem. Soc. 2007, 129, 290-291; (b) Ito, M.; Koo, L. W.; Himizu, A.; Kobayashi, C.; Sakaguchi, A.; Ikariya, T., Angew. Chem. Int. Ed. 2009, 48, 1324-1327; (c) Ito, M.; Kobayashi, C.; Himizu, A.; Ikariya, T., J. Am Chem Soc. 2010, 132, 11414-11415.18. (a) Kuhl, O., Chem. Soc. Rev. 2007, 36, 592-607; (b) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (c) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (d) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676; (e) Corberan, R.; Mas-Marza, E.; Peris, E., Eur. J. Inorg. Chem. 2009, 1700-1716.

TOF up to 880 h-1

RuCl NNN

CH3

HH

HOBase, iPrOH

O

75°C

13 cat.

PF6

H

+


5.3.1 H2-Hydrogenation of Acetophenone Catalyzed by Complex 13. The results pertaining to

the catalytic activity of complex 13 in the H2-hydrogenation of acetophenone are given in Table

5.1. Full conversion to 1-phenylethanol is achieved in 1.5 h under 25 bar of H2 in 2-propanol at

50°C with a catalyst to base to substrate (C/B/S) ratio of 1/8/200 on activation in the presence of

potassium tert-butoxide (KOtBu) as the base. This took somewhat longer (2 h) when an aprotic

solvent, tetrahydrofuran (THF), was used instead (Table 5.1, entries 1 and 2). The ruthenium(II)

complex is not a catalyst when not activated by base. It exhibited low activity when sodium tert-

butoxide, which has a low solubility in THF, was used. In addition, the ruthenium(II) complex is

not a catalyst when activated by base in the absence of H2 in THF (Table 5.1, entries 3, 4 and 8).

More importantly, an increase in substrate loading to a catalyst to substrate (C/S) ratio of 1/1200

decreased the TOF value by 3-fold, giving a value of 73 h-1 (Table 5.1, entries 6 and 7). The

catalyst [RuCp*(C–NH2)(py)]PF6 (15, Cp* = pentamethylcyclopentadienyl; py = pyridine, see

Chapter 4), which contains the same chelating primary amine-NHC ligand, tolerates high

substrate loading (C/S ratio up to 1/11500) when activated by base.21

On the other hand, the osmium(II) complex, [Os(p-cymene)(C–NH2)Cl]PF6 (14, see Chapter

4),20 when activated by base (KOtBu) in THF, gave 23% conversion to 1-phenylethanol using 25

bar of H2 as the hydrogen source (C/B/S=1/8/200) in 3 h at 50°C. It gave 99% conversion in 20 h

at 50°C if 2-propanol was used as solvent. This has lower activity in the H2-hydrogenation of

acetophenone compared to its ruthenium(II) counterpart.

19. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 6755-6761.20. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2011, 30, 1236-1252.21. O, W. W. N.; Lough, A. J.; Morris, R. H., Chem. Commun. 2010, 46, 8240-8242.

111Table 5.1. H2-Hydrogenation of Acetophenone to 1-Phenylethanol Catalyzed by Complex 13.

O 13 cat.

H2, Base50oC

HO H

Entrya C/B/Sb

ratioSolvent Base Conversionc (%/h) TOFd /h-1

1 1/8/200 iPrOH KOtBu 96/1 99/1.5 2872 1/8/200 THF KOtBu 88/1 99/2 2133 1/8/200 THF NaOtBu 5/1 11/2 -e

4 1/0/200 THF none 0/1 05 0/8/200 THF KOtBu 0/1 06 1/8/600 THF KOtBu 20/1 57/2.5 1227 1/8/1200 THF KOtBu 6/1 28/3 738f 1/8/200 THF KOtBu 0/1 0

a Reactions were carried out in a 50mL Parr hydrogenation reactor at 25 bar of H2 pressure at

50°C using THF or iPrOH (6 mL) as the solvent. b C/B/S = catalyst to base to substrate ratio. c

Conversions were determined by GC and are reported as an average of two runs. d TOF =

turnover frequency, measured from the slope of the linear portion of an [alcohol] versus time

plot. eTOF not measured. fReaction conducted under argon.

5.3.2 H2-Hydrogenation of Other Ketones Catalyzed by Complex 13. Other ketones with

different steric bulk were investigated (Table 5.2, entries 1-6). In general, TOF values increase

with a larger group next to the polar bond. Of note, substrates without α-C–H protons next to the

carbonyl group did not show inhibition of the catalysis by the substrate. For example, a 2-fold

increase in the substrate loading in the hydrogenation of benzophenone gave similar initial rates

and TOF values (Table 5.2, entries 2 and 3, Figure 5.2). On the other hand, complex 13 did not

catalyze the hydrogenation of deoxybenzoin in basic THF (entry 6). All these results are

suggestive of the formation of an enolate complex derived from the active ruthenium species.

This likely causes a decrease in the concentration of the active ruthenium species within the

catalytic cycle (vide infra). An increase in the donor ability on going from chloro to methoxy

substituents at the 4'-position of the aryl group on the ketone led to a slight decrease in the TOF

values (entries 7 and 8). Placing the chloro group ortho to the ketone results in a dramatic

112decrease in rate (entry 9). Pinacolone and benzaldehyde were also effectively hydrogenated

under similar reaction conditions (entries 10 and 11).

Table 5.2. H2-Hydrogenation of Ketones Catalyzed by Complex 13.

O O O O

OCl

OOCH3

OCl

O O

H

O

a b c d e

f g h i j

Entrya Substrate Conversionc (%/h) TOF/h-1

1 a 88/1 99/2 2132 b 78/1 98/2 2083b b 40/1 77/3 1794 c 94/1 99/1.5 4615 d 94/1 99/1.5 3776 e 0/1 0/2 07 f 94/1 99/1.5 2608 g 79/1 96/2.5 2159 h 3/1 4/1.5 510 i 74/1 99/2.5 16411 j 70/0.16 99/0.5 838

a Reactions were carried out in a 50 mL Parr hydrogenation reactor at 25 bar of H2 pressure at

50°C using THF (6 mL). KOtBu was used as base. The C/B/S ratio was 1/8/200. b The C/B/S

ratio was 1/8/400. c Conversions were determined by GC and are reported as an average of two

runs.

113

Figure 5.2. Catalytic H2-hydrogenation of benzophenone to benzhydrol (Table 5.2, entries 2 and

3) in the presence of catalyst 13, KOtBu, and THF (6 mL) in 25 bar of H2 pressure at 50°C with a

C/B/S ratio of (a) 1/8/200 (triangles) and (b) 1/8/400 (squares).

5.3.3 Kinetic Studies. The mechanism of action of the H2-hydrogenation of ketones catalyzed by

complex 13 was probed by determining the rate law. Acetophenone was chosen as the substrate

of interest, and its concentration along with that of 1-phenylethanol was conveniently monitored

by gas chromatography (GC). The catalytic conditions were varied from the standard conditions

(0.83 mM [13], 25 bar of H2, 0.17 M acetophenone and 7.4 mM KOtBu; catalyst/base/H2/ketone

= 1/8/120/200) by changing the concentration of a single component of interest, using 0.28 –

0.83 mM of 13, 5 – 25 bar of H2, 0.17 – 1.0 M acetophenone, 0 – 35 mM 1-phenylethanol, and

2.9 – 18 mM KOtBu. The reaction temperature was kept at 50°C for all of the runs. Some

representative catalytic conditions and kinetic data from the initial linear portion of the plots of

[alcohol] versus time are given in Figure 5.3 and in Table 5.3.

114(a)

(b)

(c)

115(d)

(e)


catalyzed by complex 13 in basic THF: (a) dependence on the catalyst concentration (13); (b)

dependence on the hydrogen concentration; (c) dependence on the acetophenone concentration;

(d) dependence on the base concentration (KOtBu); (e) dependence on the 1-phenylethanol

concentration. The inset shows the dependence of initial rates (v0, 10-5 M s-1) and the

concentration of the analyte of interest.

Under pseudo-first-order conditions, it was determined that the rates, within experimental

error, are first order in the concentrations of the complex 13 and of hydrogen. A plot of the initial

rate (v0, in M s-1) versus [13] (in mM) yielded a straight line with a slope of (60 ± 1) × 10-3 s-1,

while that of v0 versus [H2] in THF22 gave a straight line with a slope of (48 ± 1) × 10-5 s-1. Each

116plot passed through the origin. A plot of initial rate (in M s-1) versus [ketone] (in M) yielded a

hyperbola which does not pass through the origin (Figure 5.3) and gave a reaction order of -0.6

on the ketone. The rate law, on the other hand, is zero order in the concentrations of 1-

phenylethanol and KOtBu within the range of concentrations of interest (vide infra).

A possible general form of the course of the reaction is proposed as shown in Scheme 5.1 to

explain the kinetic data and the experimental findings. First, an active species is quickly formed

by the reaction of complex 13 with a base. This species can then either reversibly react with

acetophenone (Keq(H/D)) to produce an enolate complex or, in the rate-determining step (kH/D),

irreversibly react with hydrogen (or deuterium) gas to give a second reactive ruthenium complex

responsible for the reduction of the ketone to the product alcohol. This second complex is likely

to be a hydride (or deuteride) formed by the heterolytic splitting of dihydrogen (or dideuterium).

Similar observations were reported in the H2-hydrogenation of acetophenone using the

precatalyst trans-RuHCl-(κ4(P,N,N,P)-(S,S)-cyP2(NH)2) when activated by base under 12 bar of

H2 in 2-propanol at 20°C: a 3-fold increase in the C/S ratio to 1/12500 led to a decrease in the

initial rate by 25%.12d For the system which might undergo the outer-sphere bifunctional

mechanism, it was postulated that a reversible reaction between acetophenone and the

ruthenium-amido complex RuH(κ4(P,N,N,P)-(S,S)-cyP2(NH)-(NH2)) forms the ruthenium-ketone

adduct, and this equilibrium outcompetes the coordination of dihydrogen to ruthenium. This had

the effect of slowing catalysis, since it was proposed that the heterolytic splitting of η2-H2 by the

amido complex to afford the bifunctional dihydride catalyst trans-Ru(H)2(κ4(P,N,N,P)-(S,S)-

cyP2(NH)2) was rate-limiting. The binding of the ketone to the amido complex might also lead to

the formation of a stable enolate complex: this could occur by the deprotonation of an α-C–H

proton from the coordinated acetophenone by the ruthenium-amido complex (Scheme 5.1).

22. This was modeled using the data obtained for 1,2-dimethoxyethane at 323K. The Henry's Law constant for the solubility of H2 in THF at 50°C was therefore modeled to 3.98 × 10-2 M/bar, see: Solubility Data Series, Hydrogen and Deuterium, 5/6; Young, C. L., Ed.; Pergamon Press: New York, 1981.

117Scheme 5.1. Reaction Scheme Showing the Definitions of the Rate and Equilibrium Constants.

The rate law (eq 5.1) can be derived from this general reaction scheme (see the Appendix for

derivation):

rate =−d [ ketone]

dt=

k H[Ru ]tot [H2]1+K eq[ ketone]

(5.1)

in which [Ru]tot is the total concentration of ruthenium species, after complex 13 is activated

with base. This suggests that [13] is equal to [Ru]tot if catalyst decomposition does not occur. By

taking the reciprocal of eq 5.1, the reciprocal of the rate and the ketone concentration is related

by eq 5.2.

1rate

= 1k H[Ru]tot[H2]

+K eq[ ketone]

k H [Ru]tot [H2](5.2)

This will allow the calculation of kH and Keq values, respectively, using the slope and the y

intercept of such a linear plot. Indeed, a plot of the reciprocal of initial rate (in M-1 s) versus

[acetophenone] (in M) using the kinetic data is linear with a y intercept of (12.9 ± 0.7) × 103 M-1

s-1 and a slope of (46.6 ± 1.2) × 103 M-2 s-1 (Figure 5.4). Thus the rate and equilibrium constants

obtained using the rate law given in eq 5.1 for the range of acetophenone, complex 13, hydrogen,

1-phenylethanol and base concentrations studied are

kH = 0.94 ± 0.05 M-1 s-1

[Ru](H+/D+)

O

H H

O

O

-

[Ru]

+Keq(H/D) kH/D

+ H2/D2 [Ru](H+/D+)

H/D

RuCl NNN

CH3

HH

13

PF6 KO tBu++

Keq(H/D)=[Ru]

[Ru-enolate] [acetophenone][Ru-enolate]

118Keq = 3.6 ± 0.2 at 323 K

The Keq value was also used to calculate the rate constant kH from the plots of initial rate

versus [13] or [H2], and the values obtained are within experimental error compared to the value

obtained from the plot of reciprocal of initial rate versus [acetophenone]. The observed and

calculated initial rates given in Table 5.3 also are in good agreement.

Table 5.3. Kinetic Data for the Hydrogenation of Acetophenone Catalyzed by Complex 13.

Runa [13], mM

H2

pressure, bar

[H2]b, mM

[Acetophenone], M

[KOtBu], mM

[1-Phenyl-ethanol],

mM

Initial rate (v0),× 10-5 M s-1

exptlc calcdd

1 0.28 25 100 0.17 7.4 0 1.7 ± 0.1 1.6 ± 0.12 0.55 25 100 0.17 7.4 0 3.4 ± 0.2 3.2 ± 0.33 0.83 25 100 0.17 7.4 0 4.9 ± 0.1 4.8 ± 0.44 0.83 15 60 0.17 7.4 0 2.9 ± 0.2 2.9 ± 0.25 0.83 8 32 0.17 7.4 0 1.5 ± 0.1 1.5 ± 0.016 0.83 5 20 0.17 7.4 0 0.76 ± 0.01 0.97 ± 0.087 0.83 25 100 0.33 7.4 0 3.4 ± 0.3 3.6 ± 0.38 0.83 25 100 0.50 7.4 0 2.8 ± 0.3 2.8 ± 0.29 0.83 25 100 1.0 7.4 0 1.7 ± 0.1 1.7 ± 0.110 0.83 25 100 0.17 3.0 0 5.2 ± 0.1 4.8 ± 0.411 0.83 25 100 0.17 13 0 4.5 ± 0.1 4.8 ± 0.412 0.83 25 100 0.17 18 0 3.8 ± 0.4 4.8 ± 0.413 0.83 25 100 0.17 7.4 14 4.9 ± 0.3 4.8 ± 0.414 0.83 25 100 0.17 7.4 25 5.0 ± 0.3 4.8 ± 0.415 0.83 25 100 0.17 7.4 35 5.3 ± 0.4 4.8 ± 0.4

a Reactions were carried out in a 50 mL Parr hydrogenation reactor at the required conditions at

50°C. THF (6 mL) was the solvent, and KOtBu was used as the base. b The Henry’s Law

constant for the solubility of H2 in THF at 50°C is 3.98 × 10-2.22 c Values obtained from the least-

squares fits of the data plotted in Figures 3 and 4. d Values calculated from the proposed rate law

given by eq 5.1.

119

Figure 5.4. Linear plot showing the relationship between the reciprocal of the initial rate (1/v0 in

103 M-1 s) and acetophenone concentration (M). The rate (kH) and equilibrium (Keq) constants

were derived from the slope and the y intercept according to eq 5.2, respectively.

5.3.4 Effect of the Base on Catalysis. The relationship between the concentration of potassium

tert-butoxide (KOtBu) and rates were examined by means of kinetic studies. A plot of initial rate

(in M s-1) versus [KOtBu] (in M) yielded a straight line with a slope of – (9.5 ± 1.3) × 10-4 s-1

which does not pass through the origin (Figure 5.3). The reaction order was -0.2, as determined

by the kinetic data. The concentration of the alkoxide base, therefore, does not greatly influence

the rate of catalysis. In addition, potassium tert-butoxide in high concentrations is known to form

stable aggregates in solvents with low dielectric constants, such as THF. For instance, the

reaction of Pt(papH)Cl (papH = κ3(C,N,N)-2-phenyl-6-(2 aminoisopropyl)pyridine) with 5 equiv

of KOtBu in benzene afforded the amido complex [Pt(pap)]2(KOtBu)8(KCl).23 The chloride

anion was encapsulated by seven potassium ions, and the potassium ions were bridged by

oxygens of the tert-butoxide anions. The decrease in rate in catalysis with an increasing

concentration of the base (up to 18 mM) can plausibly be attributed to complex ion-pairing and

aggregation effects between cationic potassium and ruthenium species with the anionic tert-

butoxide, the enolate of acetophenone, and the alkoxide of 1-phenylethanol. Potassium ions are

known to form solvates with THF molecules, but these are weak in comparison to strong anion-

23. Song, D.; Morris, R. H., Organometallics 2004, 23, 4406-4413.

120cation ion pairing interactions. On the other hand, a decrease in rate was also observed when a

low concentration of base (1.2 mM) was used in catalysis (C/B/S = 1/1.4/200).

It has been shown that for certain transfer24 and H2-hydrogenation25 systems, particular alkali-

metal cations can accelerate the catalysis by acting as a Lewis acid. This possibility was

examined by our system. The addition of [2.2.2]cryptand in equimolar amount to potassium ions

(C/B/S = 1/1.4/200) led to comparable reaction rates with respect to the standard condition for

catalysis (C/B/S = 1/8/200). An equimolar amount of 18-crown-6 that was added with respect to

base (C/B/S=1/8/200, [KOtBu] = 7.4 mM) had no effect on the reaction rate. The use of a base

with sodium ions (NaOtBu, Table 5.1, entry 3) gave low activity in catalysis. This, however, was

attributed to the limited solubility of the base in THF solution. Therefore, the cations of the

alkoxide base do not significantly affect the rate of catalysis.12d

5.3.5 Effect of Alcohols on Catalysis. A plot of initial rate (in M s-1) versus [1-phenylethanol]

(in M) added in excess obtained in kinetic studies yielded a straight line with a slope of (1.1

± 0.5) × 10-4 s-1 which does not pass through the origin (Figure 5.3). The reaction order was -0.1,

as determined by the kinetic data. The product alcohol and 2-propanol, therefore, have minimal

effect on catalysis and do not contribute to the rate law. Of note, the rate of conversion was

somewhat higher using 2-propanol (Table 5.1), due to the combined activities of both H2 and

transfer hydrogenation.19

5.3.6 Isotope Effects and Deuterium Labelling Studies. The measurement of kinetic isotope

effects (KIE)26 is a powerful technique to gain important mechanistic insight in catalysis. The

use of both hydrogen and deuterium gas in the measurement of the kinetic isotope effect for

hydrogenation catalysts is common,9b, 27 but it is less well known for homogeneous bifunctional

catalysts for the H2-hydrogenation of polar bonds.9a, 9c Noyori and co-workers have reported a

KIE value (kH/kD) of 2 for the hydrogenation of acetophenone catalyzed by trans-RuH(η1-BH4)

((S)-tolBINAP)((S,S)-dpen) in the presence of base in H2/2-propanol versus D2/2-propanol-d8.9a

We have recently reported a KIE value of 2.0 ± 0.1 for the hydrogenation of acetophenone

24. (a) Vastila, P.; Zaitsev, A. B.; Wettergren, J.; Privalov, T.; Adolfsson, H., Chem. Eur. J. 2006, 12, 3218-3225; (b) Wettergren, J.; Buitrago, E.; Ryberg, P.; Adolfsson, H., Chem. Eur. J. 2009, 15, 5709-5718.25. Hartmann, R.; Chen, P., Angew. Chem. Int. Ed. 2001, 40, 3581-3585.26. Westheimer, F. H., Chem. Rev. 1961, 61, 265-273.27. (a) Chock, P. B.; Halpern, J., J. Am. Chem. Soc. 1966, 88, 3511- 3514; (b) Brown, J. M.; Parker, D., Organometallics 1982, 1, 950-956; (c) Kitamura, M.; Tsukamoto, M.; Bessho, Y.; Yoshimura, M.; Kobs, U.; Widhalm, M.; Noyori, R., J. Am. Chem. Soc. 2002, 124, 6649-6667; (d) Imamoto, T.; Itoh, T.; Yoshida, K.; Gridnev, I. D., Chem. Asian J. 2008, 3, 1636-1641.

121catalyzed by trans-Ru(H)2((R)-BINAP)(tmen). This was interpreted as an early transition state

involving the heterolytic splitting of dihydrogen (dideuterium) by the ruthenium catalyst where

there is little weakening of the H–H/D–D bond.9c

The rates of the reaction using D2 gas were examined within a given range of acetophenone

concentrations (0.083 – 0.16 M) at low D2 gas pressure (8 bar)28 and 50°C in basic THF to obtain

meaningful kinetic data. The kD and Keq(D) values were calculated from the slope and y intercept

of a plot of the reciprocal of the initial rate (in M-1 s) and [acetophenone] (in M) as in eq 5.2.

This gave a linear plot with a y intercept of (51 ± 5) × 103 M-1 s-1 and a slope of (15 ± 4) × 104

M-2 s-1 The catalysis conditions along with the results of the kinetic data and calculated values of

kD and Keq(D) are given in Figures 5.5 and 5.6, and in Tables 5.4 and 5.5. The experimentally

determined kinetic isotope effect value (kH/kD), within experimental error, is 1.33 ± 0.15 for

using H2 versus D2 gas.

Since the presence of α-C–H groups adjacent to the carbonyl group of a ketone was shown to

inhibit catalysis by allowing enolate formation, it was important to determine the effect of

deuteration of these positions in acetophenone. Kinetic studies were therefore performed using

acetophenone-d3 (0.16 – 0.49 M) at 25 bar of H2 and 50°C in basic THF. The kD and Keq(D)

values were computed in a fashion similar to that described above by first plotting the reciprocal

of initial rate (in M-1 s) versus [acetophenone-d3] (in M, Figure 5.6) to yield a y intercept of (17

± 1) × 103 M-1 s-1 and a slope of (22 ± 3) × 103 M-2 s-1. The catalysis conditions, results of the

kinetic data, and calculated values of kD and Keq(D) are given in Figures 5.5 and 5.6, and in Tables

5.4 and 5.5.

28. Deuterium gas is 1.046 times more soluble than hydrogen gas in water at 50°C; see Muccitelli, J.; Wen, W. Y., J. Solut. Chem. 1978, 7, 257-267.

122(a)

(b)


catalyzed by complex 13 in basic THF: (a) under 8 bar of D2 gas with different concentrations of

acetophenone; (b) under 25 bar of H2 gas with different concentrations of acetophenone-d3.

The deuterated products were examined by NMR spectroscopy. For catalysis using 8 bar of

D2 gas (C/B/S = 1/8/200) at 50°C, deuterium incorporation into the methyl groups of the

unreacted acetophenone and of the product 1-phenylethanol was observed at 50% conversion by

use of 1H (in CDCl3) and 2H NMR analysis, with C6D6 serving as an external reference.

Deuteration of the phenyl ring as a result of C–H activation of acetophenone was not observed.

Deuteration by D2 gas at the hydroxyl group and the α-carbon were observed (>81%

123enrichment). Likewise, for catalysis using acetophenone-d3 and 25 bar of H2 gas (C/B/S =

1/8/200) at 50°C, hydrogen scrambling with deuterium in the methyl group was observed in both

acetophenone and 1-phenylethanol at 91% conversion. Deuteration at the hydroxyl group and the

α-carbon were negligible (<3% enrichment). Deuterium scrambling into the methyl group of the

acetophenone and 1-phenylethanol may occur via protonation/deuteration of an enolate complex,

since a stoichiometric reaction of acetophenone-d3 and 1-phenylethanol in basic THF under an

argon atmosphere at 50°C also leads to deuterium/proton scrambling in the methyl group of the

ketone but not in the alcohol. The former could also occur by H/D exchange with the amine

ligand or with the hydroxyl group of coordinated 1-phenylethanol or tert-butanol. The formation

of stable ruthenium(II) complexes containing strong deuterium-heteroatom bonds in the ligands

and a strong ruthenium-deuteride bond is thermodynamically favored. This makes the transfer of

D+/D- to the ketone from the metal difficult.

Figure 5.6. Linear plots showing the relationship between the reciprocal of the initial rate (1/v0

in 103 M-1 s) and acetophenone concentration (M), using (a) D2 gas (8 bar) and acetophenone, (b)

H2 gas (25 bar) and acetophenone, and (c) H2 gas (25 bar) and acetophenone-d3 (0.16 – 0.49 M),

in the production of 1-phenylethanol from acetophenone catalyzed by complex 13 in basic THF.

The use of D2 and acetophenone-d3 as deuterium sources helps to confirm the rate law

equation and the kinetic model shown in Scheme 5.1. If the heterolytic splitting of dihydrogen is

the rate-determining step in the catalytic cycle, the use of acetophenone-d3 as a substrate should

have a small kinetic isotope effect on kH but a large isotope effect on the equilibrium between the

active species and the enolate complex. This is exactly what is observed. On the other hand, the

124use of D2 gas gave a kinetic isotope effect but had little influence on the equilibrium between the

active species and the enolate complex. The equilibrium constant values for enolate formation

decrease as the number of deuterium atoms available in the system increases on going from the

use of a protic source (H2, acetophenone) to a partially deuterated ketone (H2, acetophenone-d3)

(Scheme 5.1 and Table 5.5). We conclude that the small kinetic isotope effect that is observed

upon the use of D2 gas in the reduction of acetophenone is indicative of an early transition state

in the heterolytic splitting of H29c combined with an expected inverse equilibrium isotope effect

for the H2/D2 binding to the active ruthenium species.29

Table 5.4. Kinetic Data for Kinetic Isotope Effect Studies of the Hydrogenation of

Acetophenone Catalyzed by Complex 13.

Runa [13], mM

H2 pressure, bar

[H2/D2]b, mM

[Acetophenone/ acetophenone-d3], M

[KOtBu], mM

Experimental initial ratec (v0), × 10-5 M s-1

1d 0.83 8 33 0.083 7.4 1.54 ± 0.062d 0.83 8 33 0.12 7.4 1.46 ± 0.103d 0.83 8 33 0.17 7.4 1.29 ± 0.074e 0.83 25 100 0.16 7.4 4.9 ± 0.25e 0.83 25 100 0.32 7.4 4.3 ± 0.26e 0.83 25 100 0.48 7.4 3.6 ± 0.1

a Reactions were carried out in a 50 mL Parr hydrogenation reactor at the required conditions at

50°C. THF (6 mL) was the solvent, and KOtBu was used as the base. b The Henry’s Law

constant for the solubility of H2 in THF at 50°C is 3.98 × 10-2.22 Deuterium gas is 1.046 times

more soluble than hydrogen gas in water at 50°C.28 c Values obtained from the least-squares fits

of the data plotted in Figure 5.5. d Run 1 to 3: D2 was used as the deuterium source. e Run 4 to 6:

Acetophenone-d3 was used as the deuterium source.

Table 5.5. Isotope Effect for the Hydrogenation of Acetophenone Catalyzed by Complex 13.

Deuterium source kD (M-1 s-1)b Keq(D)b KIE (kH/kD)D2 (8 bar, 33 mM) 0.70 ± 0.07 2.9 ± 0.8 1.33 ± 0.15

Acetophenone-d3 (0.16-0.49 M) 0.72 ± 0.05 1.3 ± 0.2 1.29 ± 0.11

a Values obtained from the slopes and intercepts of the linear plots given in Figure 5.6 and eq

5.2.

29. Parkin, G., Acc. Chem. Res. 2009, 42, 315-325 and references therein.

1255.3.7 The Disfavored Outer-Sphere Bifunctional Mechanism. Two mechanistic proposals

should be considered in light of the experimental findings described above. While the outer-

sphere bifunctional mechanism6b is expected, there is stronger evidence for an inner-sphere

mechanism as described below. In an outer-sphere mechanism which would involve the

bifunctional nature of a primary amine group (NH2) and the metal-hydride bond (Ru–H), the

activation of complex 13 with base should give a metal-amido complex containing a trigonal-

planar nitrogen donor atom (Scheme 5.2). Coordination of dihydrogen to such a complex and

subsequent heterolytic splitting of the molecule should give the bifunctional metal-hydride and

protic amine grouping. The hydride and the proton equivalent would then transfer to the ketone

in the outer coordination sphere, giving the product alcohol, without coordination to the metal

center. In this mechanism the observed inhibition by enolizable ketones would be explained by

the reaction of the ketone with the metal-amido complex.12d Deprotonation of the methyl group

should afford the enolate complex with the primary amine group restored.

Scheme 5.2. Possible Outer-Sphere Mechanism That Involves Bifunctional Catalysis in the

Hydrogenation of Acetophenone.

Ru NNN

CH3

H

RuH NNN

CH3

HH

O

RuH NNN

CH3

HH

17

Ru NNN

CH3

H

HH

Ru NNN

CH3

H

OH

HH

O

O

-

KOtBu - KCl- HOtBu

RuCl NNN

CH3

HH

13

PF6+

H2

- H2

OOH

H

+

+

+

+

+

126In order to identify reaction intermediates in the outer-sphere mechanism, reactions of excess

or stoichiometric amounts of base (KOtBu, KH, NaBH4, or K-Selectride) with complex 13 in

THF were tried, but these gave multiple unidentifiable products. Attempts to isolate such

products failed and instead led to instant decomposition. Attempts to prepare the ruthenium-

hydride complex 17 ([Ru(p-cymene)(C–NH2)H]PF6, Scheme 5.2) by using dihydrogen (up to 5

bar) in excess KOtBu in stirring THF at 25 or 50°C also failed. However, complex 17 could be

prepared by warming complex 13 and 3 equiv of sodium 2-propoxide in 2-propanol solution at

50°C for 3 h, giving a brown solid upon isolation in 57% yield (Scheme 5.3). The use of KOtBu

or a reaction that was conducted in refluxing 2-propanol gave impure products. Complex 17 is

oxygen sensitive both in solution and in the solid state. A solution of 17 in dichloromethane

readily converts to the cation of complex 13 at room temperature in hours and slowly reacts with

solvents such as acetonitrile after prolonged standing for days.

Scheme 5.3. Synthesis of Complex 17 from Reaction of Complex 13 and Basic 2-Propanol.

Complex 17 was unambiguously characterized by an X-ray diffraction study (Figure 5.7). The

compound adopts a piano-stool geometry about the metal center. The Ru–Ccarbene bond (2.029(7)

Å) was shorter than that of complex 13 (2.092(5)Å).19 The large bite angle between the carbene

and primary amine donor containing the metal center (C(1)-Ru(1)-N(3) = 91.9(2)°) is typical of

L–Ru–L angles for ruthenium arene complexes [Ru(η6-arene)HL2]+ containing a hydride

ligand.5, 11c, 30 Note that the contact distance of 2.45 Å between the ruthenium hydride and the

primary amine protons (Ru–H⋅⋅⋅H–N–) is comparable to that for the complex RuH(η6-p-cymene)

((S,S)-Tsdpen) (contact distance 2.29 Å) reported by Noyori and co-workers.5 In solution, the

Ru–Ccarbene resonance was observed at 185.3 ppm in the 13C{1H} NMR spectrum. The Ru–H

resonance was observed at -7.82 ppm in the 1H NMR spectrum in CD3CN. This lies in the region

for analogous ruthenium-hydride complexes of the type [Ru(η6-arene)HL2]+.5, 11c, 30

30. Chaplin, A. B.; Dyson, P. J., Organometallics 2007, 26, 4357-4360.

RuCl NNN

CH3

HH

3 NaOiPr RuH NNN

CH3

HH

PF6 PF6

13 17

+ +iPrOH, 50°C

127

Figure 5.7. ORTEP diagram of 17⋅THF depicted with thermal ellipsoids at the 30% probability

level. The counteranion, solvent molecule, and most of the hydrogens have been omitted for

clarity. Selected bond distances (Å) and bond angles (deg): Ru(1)-C(1), 2.029(7); Ru-(1)-N(3),

2.145(5); Ru(1)-H(1ru), 1.79(7); Ru(1)-C(15), 2.232(6); C(1)-Ru(1)-N(3), 91.9(2); C(1)-Ru(1)-

H(1ru), 81(2); H(1ru)-Ru(1)-N(3), 84(2).

The catalytic activity of the hydride complex 17 was then tested under H2-hydrogenation (25

bar, 50°C in THF or 2-propanol) and transfer hydrogenation (75°C in 2-propanol) conditions. No

catalytic activity was observed in the H2 hydrogenation of acetophenone in the absence of base

when a C/S ratio of 1/200 was used. A conversion of 3% to 1-phenylethanol and a maximum

conversion of 9% were achieved in 2 and 19 h, respectively, under transfer hydrogenation

conditions in the absence of base when the same C/S ratio was used. However, addition of base

(KOtBu) to such a reaction mixture activates the complex to catalyze the hydrogenation of

acetophenone. Full conversion to 1-phenylethanol is achieved in 45 min with a C/B/S ratio of

1/8/200 under identical H2-hydrogenation conditions as above and to 88% conversion in 2 h

under identical transfer hydrogenation conditions. Plots of the concentration of product alcohol

versus time for both H2-hydrogenation and transfer hydrogenation were sigmoidal with a short

induction period of 6 and 30 min, respectively (Figure 5.8). The induction period can be

explained by the conversion of 17 by reaction with the base into a catalytically active species.

The addition of 1-phenylethanol to the starting mixture led to a slower reaction rate and a slightly

longer induction period. Therefore, the alcohol does not act as a proton shuttle in the

128heterolytically splitting of H2, in contrast to other bifunctional systems that were studied.1b, 7d, 9a,

10b, 12d, 12g, 21, 31

(a)

(b)

Figure 5.8. Reaction profiles showing the hydrogenation of acetophenone catalyzed by complex

13 (blue squares) and complex 17 (red circles) in (a) basic THF at 25 bar of H2 pressure and

50°C and (b) 2-propanol at 75°C. The C/B/S ratio was 1/8/200. The transfer hydrogenation of

acetophenone catalyzed by complex 13 in basic 2-propanol was described in Chapter 4.19

31. (a) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q., J. Am Chem Soc. 2005, 127, 3100-3109; (b) Heiden, Z. M.; Rauchfuss, T. B., J. Am Chem Soc. 2009, 131, 3593-3600; (c) Casey, C. P.; Johnson, J. B.; Jiao, X. D.; Beetner, S. E.; Singer, S. W., Chem. Commun. 2010, 46, 7915-7917.

129Interestingly, the cationic complex 17 containing a ruthenium hydride and primary amine

grouping does not transfer its hydride and proton equivalent to a ketone. This was confirmed by

the lack of reaction between complex 17 and a stoichiometric amount of acetophenone in THF-d8

at 25 or 50°C. It was expected that the metal hydride and a protic amine grouping would be

suitable to effect bifunctional catalysis of polar bonds.1b, 4c, 6 The use of an N-heterocyclic

carbene as the ligand in this cationic complex clearly shows that there is no activity in this case.

Stradiotto and co-workers have recently reported a highly active zwitterionic ruthenium catalyst

containing a phosphine-amine ligand that catalyzes the transfer hydrogenation of ketones in

refluxing 2-propanol. On the other hand, the hydride complex of the ruthenium catalyst showed

no activity toward ketone reduction, regardless of whether an excess amount of base was added.

Such a hydride complex, however, has no protic N–H functionality on its ligand.11c The cationic

charge seems to reduce the nucleophilicity of the hydride ligand so that there is diminished

catalytic activity.

If the outer sphere mechanism operates in the H2-hydrogenation of ketone catalyzed by

complex 13 in basic solvents, the hydrogenation of an α,β-unsaturated ketone would most likely

afford the reduction of the carbonyl group,6b although hydrogenation of the conjugated olefin

could also occur by a 1,4-addition reaction.32 A ligand in the active ruthenium species might also

rearrange or dissociate to allow the coordination of the olefin and its reduction to occur. This was

tested using trans-4-phenyl-but-3-en-2-one as the substrate (Scheme 5.4). Under similar catalytic

conditions (C/B/S = 1/8/200, 25 bar of H2 at 50°C), complex 13 catalyzed the reduction of the

polar bond and the olefin, giving the products trans-4-phenyl-but-3-en-2-ol (33% conversion), 4-

phenylbutan-2-one (10% conversion), and the fully hydrogenated product 4-phenylbutan-2-ol

(24% conversion) in 3 h (Scheme 5.4 and Figure 5.9).

Scheme 5.4. Hydrogenation of trans-4-Phenyl-but-3-en-2-one Catalyzed by Complex 13.

32. (a) Ito, M.; Kitahara, S.; Ikariya, T., J. Am. Chem. Soc. 2005, 127, 6172-6173; (b) Ikariya, T.; Gridnev, I. D., Chem. Rec. 2009, 9, 106-123.

13 cat.

25 bar H2, KO tBuTHF, 50°C

O

OH

O

OH

33%

10%

24% in 3 hC/B/S = 1/8/200

130

Figure 5.9. Reaction profile showing the hydrogenation of trans-4-phenyl-but-3-en-2-one

catalyzed by complex 13 in basic THF at 25 bar of H2 pressure and 50°C: (blue circles) trans-4-

phenylbut-3-en-2-ol; (red squares) 4-phenylbutan-2-ol; (green triangles) 4-phenylbutan-2-one.

The C/B/S ratio was 1/8/200.

5.3.8 The Favored Inner-Sphere Mechanism. Given the experimental data that are not

supportive of the outer-sphere mechanism, an inner-sphere mechanism is proposed.4b, 6b, 33 The

ketone must coordinate to the metal center to allow the hydride migration from the metal to the

carbonyl group. To effect coordination of the ketone, the primary amine group can decoordinate

from the metal center, or the arene ligand on the ruthenium center can slip to η4 coordination

(Figure 5.10). Of note, a seven-membered ring is formed with the chelating primary amine-NHC

ligand, including the nitrogen and carbene donor and the metal center. Facile coordination and

recoordination of the tethered group can occur under catalytic conditions. This has been

proposed for the transfer hydrogenation of ketones using a complex of type Ru(η6-arene)

(κ2(N,N)-N–N)Cl (N–N = 2-hydroxylphenylbis(pyrazol-1-yl)methane and other derivatives)

under base free conditions. The authors proposed that a nitrogen donor of a pyrazolyl group

decoordinates from the metal center during catalysis and acts as a base in the deprotonation of

the coordinated alcohol.34 Elsevier and co-workers recently reported the use of N-heterocyclic

carbene complexes with a tethered tertiary-amine group of palladium(0), [Pd(NHC-amine)

(alkene)], in the transfer hydrogenation of alkynes to (Z)-alkenes under base-free conditions.

Experimental findings suggest the tethered amine group dissociates from the metal center and

acts as a base in catalysis.35 Chu and co-workers reported the use of a half-sandwich complex of

131ruthenium containing a tethered tertiary amine group on the cyclopentadienyl ligand, which acts

as a base to assist the heterolytic cleavage of dihydrogen.36 Nolan and co-workers have recently

reported the mechanism of racemization of chiral alcohols catalyzed by ruthenium(II) systems

containing N-heterocyclic carbene ligands. This was suggested to undergo an inner-sphere

mechanism which involved the dissociation of a coordinated carbonyl ligand. An Ru–

O(alkoxide) bond was formed in the presence of alkoxide, and this is responsible for the

formation of a ruthenium hydride intermediate in the racemization of chiral alcohol. This is

further supported by NMR studies and DFT computations.37 The feasibility of the amino group

dissociation has been explored using computational methods (vide infra). Of note, it is less likely

for the primary amine group to act as a base in catalysis, as complex 13 must be activated by an

alkoxide base to become active.

Figure 5.10. Possible reaction intermediates for the inner-sphere mechanism involving hydride

migration to the coordinated ketone substrate: (left) decoordination of the chelating amine group

from the NHC ligand; (right) ring slippage of the arene ring.

In order to probe the importance of the primary amine group tethered to the N-heterocyclic

carbene ligand in complex 13, we attempted to make and test the N,N-dimethylamine analogue.

Methylation of the primary amine group of complex 13 was not successful. We did succeed in

preparing a closely related compound by reaction of the imidazolium salt, 1-(N,N-dimethyl-

amino)propyl-3-methylimidazolium chloride hydrochloride (HC–NMe2⋅HCl, 1g),38 with silver(I)

oxide and [Ru(p-cymene)Cl2]2 in one pot (Scheme 5.5). Note that the carbene ligand derived

from 1g, if it chelates to the metal, will form a seven-membered ring as observed in complex 13.

The in situ generation of the silver(I) carbene complex derived from 1g and subsequent

33. Daley, C. J. A.; Bergens, S. H., J. Am. Chem. Soc. 2002, 124, 3680-3691.34. Carrion, M. C.; Sepulveda, F.; Jalon, F. A.; Manzano, B. R.; Rodriguez, A. M., Organometallics 2009, 28, 3822-3833.35. Hauwert, P.; Boerleider, R.; Warsink, S.; Weigand, J. J.; Elsevier, C. J., J. Am. Chem. Soc. 2010, 132, 16900-16910.36. Chu, H. S.; Lau, C. P.; Wong, K. Y.; Wong, W. T., Organometallics 1998, 17, 2768-2777.37. Bosson, J.; Poater, A.; Cavallo, L.; Nolan, S. P., J. Am. Chem. Soc. 2010, 132, 13146-13149.

CH3

NNRu

NH

H

O

H

+CH3

NN

RuNH

H OH +

132transmetalation of the NHC ligand to ruthenium(II),39 followed by counteranion metathesis, gave

a compound formulated on the basis of elemental analysis as [Ru(p-cymene)(C–NMe2)Cl]PF6⋅

1.5 DMSO (18, DMSO = dimethyl sulfoxide). The use of DMSO as cosolvent for the reaction is

unavoidable, as ligand 1g has limited solubility in most organic solvents except alcohols.

Attempts to isolate the intermediate silver(I) carbene complex containing the corresponding

imidazolylidene ligand failed, as this quickly decomposed.

Scheme 5.5. Synthesis of Complex 18 by in Situ Generation of the Silver(I) Carbene Complex

and Subsequent Transmetalation of the NHC Ligand to Ruthenium(II).

The NMR spectra of 18 in CD2Cl2 at 253 K indicate that compound is a mixture of two

complexes, one with a bidentate NHC ligand and another with a monodentate NHC and

coordinated DMSO ligand. Infrared spectroscopy usually provides a means of distinguishing

between O- and S-bound forms of the dimethyl sulfoxide ligand40 but did not prove helpful

because of the complex spectrum in the fingerprint region.

Complex 18 is an effective catalyst for the H2-hydrogenation of acetophenone with an activity

comparable to that of complex 13 under similar reaction conditions (C/B/S=1/10/240, 25 bar of

H2 at 50°C) in basic THF with KOtBu as a base. A conversion of 76% to 1-phenylethanol was

achieved within 2 h of reaction. Like complex 13, no induction period was observed (Figure

5.11). Therefore, the protons of the amino group in complex 13 are not needed for catalysis. This

is another example showing that the “NH effect” is not always operational in catalysts for polar

bond hydrogenation.11

38. Jimenez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A., Organometallics 2008, 27, 224-234.39. Warsink, S.; de Boer, S. Y.; Jongens, L. M.; Fu, C. F.; Liu, S. T.; Chen, J. T.; Lutz, M.; Spek, A. L.; Elsevier, C. J., Dalton Trans. 2009, 7080-7086.40. James, B. R.; Morris, R. H., Can. J. Chem. 1980, 58, 399-408.

0.5 [Ru(p-cymene)Cl2]2DMSO:CH3CN (1:4), rt

181g

N NCH3 N HCl1.5 Ag2O

AgPF6CH2Cl2, rt

[Ru(p-cymene)(C NMe2)Cl]PF6 •1.5 DMSO

133

Figure 5.11. Catalytic H2-hydrogenation of acetophenone to 1-phenylethanol in the presence of

catalyst, KOtBu, and THF (6 mL) in 25 bar of H2 pressure at 50°C with a C/B/S ratio of (a)

1/8/200 (red squares), catalyst 13, [13] = 0.83 mM and (b) 1/10/240, catalyst 18, [18] = 0.71 mM

(blue triangles).

5.3.9 Theoretical Considerations: The Outer-sphere Bifunctional Mechanism. The catalytic

cycles involved in both outer- (Scheme 5.2) and inner-sphere mechanisms (Figure 5.10 and

below) were investigated by using density functional theory (DFT) methods. A MPW1PW91

functional was chosen, as this gave better predictions of energy barriers and transition states.41

For computational ease, the p-cymene ligand was simplified to a benzene ligand. The alkoxide

base, 1-phenylethanol, and acetophenone were simplified to 2-propoxide, 2-propanol, and

acetone, respectively. The cations of the base and the counteranions of the catalytically active

species were omitted throughout the calculations.

The free energy profile for the outer-sphere mechanism is given in Figure 5.12. The

ruthenium-amido complex A1 reacts with dihydrogen to give the η2-dihydrogen complex B. The

amido nitrogen of A1 is highly charged (APT charge -0.37 ESU, Table 5.6) and has a short Ru–N

bond (1.89 Å, Figure 10). The sum of the angles around nitrogen is 358° in the optimized

structure. Therefore, the nitrogen is sp2 hybridized and the Ru–N has a double-bond character.

The Ru–N bond is longer in B (2.09 Å) and the double-bond character is lost, which allows

dihydrogen coordination to the coordinatively unsaturated complex. The energy barrier at 298 K

and 1 atm for the dihydrogen addition to A1 on going from structure B', which has the

134dihydrogen molecule outside the coordination sphere, to the transition state TSB',B is 18.0

kcal/mol uphill. The entropy change (ΔS‡) for dihydrogen coordination is -25.9 cal/(mol K). The

dihydrogen is weakly activated in the transition state and also in structure B, as the H–H

distances are short (0.76 and 0.83 Å, respectively).42 Structure B leads to the transition state

TSB,C, in which the H–H distance increases to 0.88 Å and the negative charge on nitrogen

increases from -0.37 to -0.40 ESU. Note that the energy difference between B and TSB,C is only

0.2 kcal/mol.

The heterolytic splitting of H2 by A1 leads to C, which is -39.5 kcal/mol downhill from TSB,C.

The Ru–H distance is 1.58 Å , which is similar within the ESD to the value of the Ru–H distance

(1.79(7) Å) in the crystal structure of complex 17. The single-bond character of Ru–N is retained

(2.16 Å), and the charge on nitrogen is further reduced to -0.24 ESU. The charges on ruthenium

and hydride are -0.72 and -0.042 ESU, respectively. The smaller charge on the hydride may

explain the poor activity of complex 17 toward reaction with acetophenone. The hydrides of the

model complex of a ketone hydrogenation catalyst, (OC-6-22)- Ru(H)2(PH3)2(en), have charges

of -0.20 and -0.15 ESU.9c From structure C, acetone is hydrogen-bonded to the complex,

forming D, and this goes +33.5 kcal/mol uphill from C plus acetone at 298 K and 1 atm, leading

to the transition state TSD,E, where the concerted transfer of dihydrogen to the ketone from Ru–H

and Ru–NH2 occurs via a six-membered ring transition state.4b, 6b, 7a-g, 7j The Ru–H bond is

elongated (to 1.84 Å), as is the N–H bond (from 1.02 to 1.30 Å). In addition, the C–H and C–O

bonds of the alcohol are formed simultaneously, with bond distances of 1.27 and 1.33 Å ,

respectively. The charge of ruthenium is reduced (-0.32 ESU) and the hydride is more negatively

charged (-0.43 ESU). This leads to the ruthenium-amido-isopropyl alcohol adduct E, held by

weak electrostatic interactions. The elimination of the alcohol product results in the regeneration

of the amido complex A1, which is -15.6 kcal/mol downhill from TSD,E. The alcohol could also

coordinate to the amido complex, forming F. Subsequent deprotonation of the alcohol by the

amide ligand causes the formation of the ruthenium-alkoxide complex G. This has a basic

alkoxide ligand (APT charge on O -0.82 ESU) and is more thermodynamically stable than A1

plus 2-propanol by 2.4 kcal/mol. Of note, the Ru–Ccarbene bond distances vary from 2.03 to 2.08

Å for all the computed structures, and they are comparable to those of complexes 13 and 17 in

the crystal structures (Figure 5.13).19

41. Lynch, B. J.; Truhlar, D. G., J. Phys. Chem. A 2001, 105, 2936-2941.42. Morris, R. H., Coord. Chem. Rev. 2008, 252, 2381-2394.

135

Figure 5.12. The free energy profile for an outer-sphere mechanism for the H2-hydrogenation of

acetone starting from A1 and moving to the right and the enolate formation starting from A1 and

moving to the left. The gas phase free energies (1 atm, 298 K) are reported relative to G in

kcal/mol.

The enolate complex A3 is formed from A1 via coordination of acetone, giving A2, and this

leads to the transition state TSA2,A3, where deprotonation of the methyl group occurs. This is

+17.9 kcal/mol uphill from A1 plus acetone. The product A3 is thermodynamically less stable

than A1 plus acetone by 7.3 kcal/mol (Figure 5.12). The computations thus accurately reflect

comparable energy barriers for the H2 addition and enolate formation from the amido complex

A1 (18.0 versus 17.9 kcal/mol at 298 K and 1 atm). The concerted transfer of a H+/H- pair to

acetone has a much higher barrier of +33.5 kcal/mol in comparison to the aforementioned steps,

which contradicts the experimental findings. The calculation also predicts that the ruthenium-

hydride complex C (complex 17) is the resting state of the catalytic cycle. This is more stable

than the ruthenium-alkoxide and ruthenium-amido complexes by 15.5 and 22.4 kcal/mol.

136

Figure 5.13. Selected computed structures A-C and G for the outer-sphere mechanism in the H2-

hydrogenation of acetone and the transition state structures for the heterolytic splitting of H2

(TSB,C) and for the concerted transfer of a hydride/proton pair to the ketone (TSD,E). The bond

lengths (Å) are given in the structures.

137Table 5.6. Atomic Polar Tensor (APT) Charges (in ESU) on Selected Atoms for the Computed

Structures A-C, G, TSB,C, and TSD,E.

Computed structures

APT charges (ESU)

Ru NHC-C C–O C–O N H1/N–H H2/Ru–H H3/N–H

A -0.25 0.51 - - -0.37 - - 0.088B -0.63 0.60 - - -0.37 0.18 0.31 0.063C -0.72 0.71 - - -0.24 0.15 -0.042 0.13G -0.21 0.60 0.57 -0.82 -0.29 0.23 -0.11 0.12

TSB,C -0.68 0.61 - - -0.40 0.097 0.020 0.064TSD,E -0.32 0.60 1.11 -0.88 -0.33 0.40 -0.43 0.084

5.3.10 Theoretical Considerations: The Inner-sphere Mechanism. An alternative proposal is

the inner-sphere mechanism, which involves the decoordination of the amine group from the

NHC ligand or ring slippage of the coordinated arene ring.7b The computed ring slipped

structures were higher in energy than those structures computed for the mechanism involving the

decoordination of the amine group (see below). Thus, they are not considered as the possible

intermediates (Figure 5.14).

Figure 5.14. Computed structures and energies (at 298 K and 1 atm relative to G + H2 in

kcal/mol) for the ring slippage mechanism.

Starting from the alkoxide complex G, the decoordination of the amine group is an uphill

process by +15.5 kcal/mol at 298 K and 1 atm (Figure 5.15). This process is entropically favored

(ΔS = 16.6 cal/(mol K)). This afterward provides the coordinatively unsaturated complex H,

which has a short Ru–O distance compared to G (1.90 and 2.06 Å , respectively, Figures 5.13

and 5.16). The charges on the oxygens of the alkoxide are comparable in H and G (-0.82 and

-0.77, respectively; see Tables 5.6 and 5.7). The variation in the Ru–Ccarbene bond distance is

similar to that of the outer-sphere mechanism for all of the computed structures (Figure 5.16). In

CH3

NNRu

NH

H

O

H

CH3

NNRu

NH

H

O

H

HCH3NN

Ru

NH

H

O

HH

HCH3NN

Ru

NH

H

OH

+H

+ + +

+ H2 + H2

*Free energy (kcal/mol) given in parentheses.

(25.1) (33.9) (28.7) (26.7)

138addition, the Ru–N distances are more than 5.0 Å for all of the computed structures. For all, the

dihedral angle of the phenyl and the imidazolylidene rings range from 83.3° for H and 95.0° for

K. For comparison, the dihedral angles for the crystal structures of complexes 13 and 17 are

54.6° and 54.3°.19

Figure 5.15. The free energy profile for the inner-sphere mechanism in the H2-hydrogenation of

acetone starting from H and moving to the right. The amino group is decoordinated throughout

the catalytic cycle. Moving to the left from H leads to the unstable enolate complex M. The gas

phase free energies (1 atm, 298 K) are reported relative to G, hydrogen and acetone in kcal/mol.

Coordination of molecular hydrogen in a side-on fashion to H then occurs, giving I. Both

QST3 and QST2 searches were performed, but these failed to locate a transition state for

dihydrogen addition to H. The dihydrogen is again weakly activated in I with a short H–H

distance of 0.85 Å.42 This process works against entropy (ΔS = -16.0 cal/(mol K)). Heterolytic

splitting of η2-H2 takes place through transition state TSI,J. The H–H distance increases to 0.92

Å, and the charge on oxygen increases from -0.68 to -0.73 ESU. The energy barrier for the

heterolytic splitting of H2 is +33.0 kcal/mol uphill from G plus dihydrogen or +17.5 kcal/mol

139from H plus dihydrogen at 298 K and 1 atm. The energy difference between I and TSI,J is 3.7

kcal/mol, indicative of an early transition state. Again, the heterolytic splitting of H2 is

entropically demanding (ΔS‡ = -19.9 cal/(mol K)). Similar DFT calculations were also performed

with the osmium(II) complex ([Os(p-cymene)(C–NH2)Cl]PF6, complex 14, see Chapter 4) using

the inner-sphere mechanism. The osmium(II) dihydrogen complex with a decoordinated amine

group similar to I is 30.7 kcal/mol uphill from the alkoxide complex analogous to G plus

dihydrogen. The related complex [Os(p-cymene)(NHC)(OH)]OTf (NHC = bis(2,6-diisopropyl-

phenyl)imidazol-2-ylidene, IPr), was believed to undergo an inner-sphere mechanism for the

transfer hydrogenation of aldehydes in 2-propanol solution, whereas the hydroxyl ligand acts as

an internal base in the formation of an Os–O(alkoxide) bond.43

The ruthenium-hydride complex containing a coordinated alcohol is then formed from TSI,J,

leading to J, which is -27.7 kcal/mol downhill. The structure has a short Ru–H bond (1.57 Å).

The charges on the ruthenium and the hydride are -0.52 and -0.039 ESU. Decoordination of 2-

propanol and recoordination of acetone forms K, and a further energy of +15.6 kcal/mol uphill is

required, leading to the transition state TSK,H. The hydride ligand on the ruthenium complex

attacks the coordinated acetone via a four-membered-ring transition state.4b, 6b, 37 The Ru–H bond

elongates to 1.65 Å and the Ru–O bond shortens (from 2.14 to 2.09 Å), due to an increased

charge on oxygen (from -0.57 to -0.60 ESU; see Table 5.7). Likewise, the C–H (1.58 Å) and C–

O (1.30 Å) bonds of the alcohol are formed simultaneously. The charge of ruthenium is reduced

(-0.70 ESU), and the hydride is more highly charged (-0.10 ESU). This leads to structure H and

completes the cycle.

43. Castarlenas, R.; Esteruelas, M. A.; Onate, E., Organometallics 2008, 27, 3240-3247.

140

Figure 5.16. Selected computed structures H-K for the inner-sphere mechanism involving

decoordination of the amine group of the NHC ligand in the H2-hydrogenation of ketone and the

transition state structures for the heterolytic splitting for H2 (TSI,J) and for the hydride attack on

the coordinated ketone (TSK,H). The bond lengths (Å) are given in the structures.

141Table 5.7. Atomic Polar Tensor (APT) Charges (in ESU) on Selected Atoms for the Computed

Structures H-K, TSI,J and TSK,H.

Computed structures

APT charges (ESU)

Ru NHC-C C–O C–O N H1/O–H H2/Ru–H N–Havg

H 0.13 0.44 0.49 -0.77 -0.47 - -0.096 0.16I -0.54 0.59 0.53 -0.68 -0.48 0.15 0.20 0.16J -0.52 0.66 0.55 -0.63 -0.49 0.26 -0.039 0.16K -0.62 0.69 0.82 -0.56 -0.48 - -0.028 0.16

TSI,J -0.52 0.58 0.53 -0.73 -0.48 0.39 -0.032 0.16TSK,H -0.70 0.59 0.97 -0.60 -0.47 - -0.10 0.16

The enolate complex M is formed from H upon coordination of acetone and subsequent

deprotonation of the coordinated alkoxide base. No transition state is located between structures

L and M. This is +24.8 kcal/mol uphill starting from H. All this reflects different energy barriers

for the H2-splitting and enolate formation from H (17.5 versus 24.8 kcal/mol at 298 K and 1

atm). The hydride migration step has a lower energy barrier of 19.6 kcal/mol, which coincides

with the experimental findings. Of note, the energy barrier for H2-splitting starting from the

alkoxide G plus dihydrogen is even higher (+33.0 kcal/mol), and the computations predict that

this is the resting state of the catalytic cycle. This predicts that the heterolytic splitting of

dihydrogen is truly the rate-determining step. The formation of an enolate complex, on the other

hand, should occur via the amido complex, as the energy barrier is 24.8 kcal/mol uphill starting

from G and moving successively from A1 to A2, to the transition state TSA2,A3, and then to A3

(see Figure 5.12). This has a much lower energy barrier than that starting from H. Of note, the

amido complex could form initially from the alkoxide complex and deprotonation of the amine

proton by the internal alkoxide base. Bergens and co-workers proposed a similar mechanism for

the complex RuH(OR)(diamine)((R)-BINAP).8b, 14

5.3.11 Possible Mechanism for Transfer Hydrogenation. The computations also gave

important information on the transfer hydrogenation of ketones. The transfer hydrogenation

might proceed via the outer-sphere mechanism starting from the amido complex A1, then to E,

TSD,E, and D, and finally to C, the ruthenium-hydride complex (Figure 5.12). The energy barrier

starting from A1 plus 2-propanol is +15.6 kcal/mol uphill at 298 K and 1 atm. The concerted

transfer of a H+/H- pair proceeds in a manner identical with that described for the H2-

hydrogenation, going from C to A1, with an energy barrier of +33.5 kcal/ mol. This high barrier

142argues against this mechanism, and in fact, the ruthenium-hydride complex 17 has very low

activity under transfer hydrogenation conditions in the absence of base.

For the inner-sphere mechanism, decoordination of the amine group of the NHC ligand takes

place from the 2-propoxide complex G to allow the β-hydride elimination to take place, forming

H. This proceeds through the transition state TSK,H, leading to the hydride complex K (Figure

5.15). The β-hydride elimination of the alkoxide is uphill by 6.6 kcal/mol from H. The hydride

ligand from K can then attack the carbonyl group of the substrate; this is the same step as

described in the inner-sphere H2 hydrogenation mechanism, with the same energy barrier of

+15.6 kcal/mol uphill (Figure 5.15). Overall, this has lower energy barrier compared with the

outer-sphere mechanism and seems more likely to occur during catalysis.

5.3.12 Role of Complex 17 in Catalysis. Complex 17 is not likely to be an intermediate in the

H2-hydrogenation reaction, as attempts to prepare this from complex 13 in basic THF under H2

failed. In addition, it does not react with acetophenone (see below). This, however, may be the

resting state of the catalyst in the transfer hydrogenation, as it can be prepared under similar

catalytic conditions. According to the calculations, the amine group of structure K can

recoordinate, which displaces the coordinated acetone to give structure C, which is analogous to

complex 17. This is -33.1 kcal/mol downhill from the transition state TSH,K. The fact that a base

is needed to activate complex 17 in both H2-hydrogenation and transfer hydrogenation reactions

is difficult to explain. In fact, a stoichiometric reaction of complex 17 and KOtBu in THF-d8 at

50°C under argon produces a reaction mixture that lacks a hydride signal in the 1H NMR

spectrum. Subsequent addition of a stoichiometric amount of acetophenone to this reaction

mixture did not lead to the formation of 1-phenylethanol or 1-phenylethoxide. The species that is

formed from the reaction of complex 17 and an alkoxide base may be responsible for the

activation of H2.

5.4 Conclusion

In summary, the H2-hydrogenation of ketones catalyzed by complex 13 was studied and the

mechanism of action was investigated by both experimental and theoretical means. The

ruthenium-hydride complex 17, which was thought to be the crucial intermediate for bifunctional

catalysis, was isolated. This, however, showed no activity under catalytic conditions unless when

143activated by a base. This hydride complex is believed to be the resting state in the transfer

hydrogenation mechanism. The cationic charge on the metal center is likely to decrease the

nucleophilicity of the hydride ligand. In fact, this is a rare example of a catalyst with an M–H

and N–H grouping that fails to undergo bifunctional catalysis using the “NH effect”, which was

originally proposed by Noyori and co-workers.6a Kinetic studies including the studies of isotope

effects using D2 gas and acetophenone-d3 support the theoretical predictions that an early

transition state in the heterolytic splitting of H2 is the rate-determining step of the catalytic cycle.

The outer-sphere mechanism involving bifunctional catalysis of ketone reduction is disfavored

according to experimental studies. Computational studies also suggest a high energy barrier for

the concerted transfer of H+/H- to the ketone compared to dihydrogen addition and subsequent

heterolytic splitting.

An alternative to the outer-sphere bifunctional mechanism is therefore proposed on the basis

of experimental and theoretical findings. First, complex 13, when activated, leads to a

ruthenium-alkoxide complex. The alkoxide ligand labilizes the cis-amine ligand.44

Decoordination of the amine group of the NHC ligand provides a vacant site for the coordination

of dihydrogen (Scheme 5.6). Ring-opening reactions are common for chelating ligands that form

a seven-membered ring with the metal. Catalysis then proceeds with the heterolytic splitting of

dihydrogen by the internal alkoxide base, and then hydride attacks the coordinated ketone. In

addition, the alkoxide complex can convert to the ruthenium-amido complex which is

responsible for the formation of an enolate complex. The current study should assist in the

rational design of more robust and active hydrogenation catalysts using N-heterocyclic carbenes

as ligands.

44. (a) Atwood, J. D.; Brown, T. L., J. Am. Chem. Soc. 1976, 98, 3160-3166; (b) Bryndza, H. E.; Domaille, P. J.; Paciello, R. A.; Bercaw, J. E., Organometallics 1989, 8, 379-385; (c) Caulton, K. G., New J. Chem. 1994, 18, 25-41; (d) Flood, T. C.; Lim, J. K.; Deming, M. A.; Keung, W., Organometallics 2000, 19, 1166-1174.

144Scheme 5.6. Proposed Mechanism for the H2-Hydrogenation of Ketones Catalyzed by Complex

13 and an Alkoxide Base.



carried out under a nitrogen or argon atmosphere using standard Schlenk-line and glovebox

techniques. Dry and oxygen-free solvents were always used. The synthesis of [1-(2-(amino-

methyl)phenyl)-3-methylimidazol-2-ylidene]chloro(η6-p-cymene)ruthenium(II) hexafluoro-

phosphate (13) has been described in Chapter 4.19 The synthesis of 1-(N,N-

dimethylamino)propyl-3-methylimidazolium chloride hydrochloride (1g)38 and [Ru(p-

cymene)Cl2]245 were reported in the literature. All other reagents and solvents were purchased

from commercial sources and were used as received. Deuterated solvents were purchased from

Cambridge Isotope Laboratories and Sigma Aldrich and degassed and dried over activated 45. Bennett, M. A.; Smith, A. K., Dalton Trans. 1974, 233-241.

CH3NN

RuNH

H HR'

O

CH3NN

RuNH

H O

R'

H

Ru NNN

CH3

H

OR'

H

H

H2

OR'

CH3NN

RuNH

H R'O HHH

CH3NN

RuNH

H HO

R'

R

R

R

R

R

R

Ru NNN

CH3

HRu N

NN

CH3

H

OR''

H H-

++O

R'

R

OR'

R

R HOH R'

R

HOH R'

R-

HOH R'

R

+

+

+

+

+

145molecular sieves prior to use. NMR spectra were recorded on a Varian 400 spectrometer

operating at 400 MHz for 1H, 100 MHz for 13C, and 376 MHz for 19F. The 1H and 13C{1H} NMR

spectra were measured relative to partially deuterated solvent peaks but are reported relative to

tetramethylsilane (TMS). All 19F chemical shifts were measured relative to

trichlorofluoromethane as an external reference. Elemental analyses were performed at the

Department of Chemistry, University of Toronto, on a Perkin-Elmer 2400 CHN elemental

analyzer. Samples were handled under argon where it was appropriate. Single-crystal X-ray

diffraction data were collected using a Nonius Kappa-CCD diffractometer with Mo Kα radiation

(λ = 0.71073 Å). The CCD data were integrated and scaled using the Denzo-SMN package. The

structures were solved and refined using SHELXTL V6.1. Refinement was by full-matrix least

squares on F2 using all data.

5.5.2 Synthesis of [1-(2-(Aminomethyl)phenyl)-3-methylimidazol-2-ylidene]hydrido(η6-p-

cymene)ruthenium(II) Hexafluorophosphate ([Ru(p-cymene)(C–NH2)H]PF6, 17). A Schlenk

flask was charged with 13 (50 mg, 0.083 mmol) in 2-propanol solution (14 mL). The solution

was warmed to 50°C under an argon atmosphere. A solution of sodium 2-propoxide (20 mg, 0.24

mmol) in 2-propanol (6 mL) was added to this stirred solution over the course of 0.5 h,

whereupon the color of the reaction mixture turned from yellow to deep red and then to brown.

The solution was stirred for a further 3 h. After the reaction had gone to completion, the solvent

was removed under vacuum. The solid residue was extracted with tetrahydrofuran (THF, 4 mL)

and filtered through a pad of Celite. The addition of pentane (16 mL) to the THF solution yielded

a brown precipitate, which was collected and dried in vacuo. Yield: 27 mg, 57%. Crystals

suitable for an X-ray diffraction study were obtained as a THF solvate by slow diffusion of

pentane into a saturated solution of 17 in tetrahydrofuran under a nitrogen atmosphere. 1H NMR

(CD3CN, δ): 7.56 (m, 3-CH and 4-CH of Ph, 2H), 7.46 (m, 5-CH of Ph, 1H), 7.39 (d, JHH = 7.34

Hz, 6-CH of Ph, 1H), 7.33 (d, JHH = 1.72 Hz, 5-CH of imid, 1H), 7.21 (d, JHH = 1.72 Hz, 4-CH

of imid, 1H), 5.06 (d, JHH = 5.65 Hz, 2-Ar-CH of p-cymene, 1H), 5.02 (d, JHH = 5.92 Hz, 6-Ar-

CH of p-cymene, 1H), 4.82 (d, JHH = 5.92 Hz, 5-Ar-CH of p-cymene, 1H), 4.40 (d, JHH = 5.65

Hz, 3-Ar-CH of p-cymene, 1H), 3.68 (m, CH2, 1H), 3.61 (s, CH3, 3H), 3.40 (m, br, NH2, 2H),

2.64 (dt, JHH = 3.66, 12.17 Hz, CH2, 1H), 2.40 (sept, JHH = 6.80 Hz, CH of (CH3)2CH of p-

cymene, 1H), 1.52 (s, CH3 of p-cymene, 3H), 1.21 (d, JHH = 6.80 Hz, CH3 of (CH3)2CH of p-

cymene, 3H), 1.14 (d, JHH = 6.80 Hz, CH3 of (CH3)2CH of p-cymene, 3H), -7.82 (s, Ru–H). 19F

NMR (CD3CN, δ): -72.9 (d, JPF = 706 Hz). 13C{1H} NMR (CD3CN, δ): 185.3 (Ru–C), 141.4

146(CPh), 134.0 (CPh), 132.2 (CPh), 130.5 (CPh), 129.3 (CPh), 126.6 (CPh), 124.3 (Cimid.), 123.5 (Cimid.),

108.7 (CAr-p-cymene), 105.1 (CAr-p-cymene), 88.9 (CAr-p-cymene), 85.6 (CAr-p-cymene), 81.3 (CAr-p-cymene),

80.9 (CAr-p-cymene), 47.4 (CH2), 39.8 (CH3), 32.4 (CH of (CH3)2CH of p-cymene), 24.1 (CH3 of

(CH3)2CH of p-cymene), 23.9 (CH3 of (CH3)2CH of p-cymene), 19.1 (CH3 of p-cymene). MS

(ESI, methanol/water; m/z): 424.1 ([M]+). Attempts at elemental analyses failed to give an

acceptable carbon content, while hydrogen and nitrogen contents are in the acceptable range.

Typical results are as follows. Anal. Calcd for C21H28F6N3PRu: C, 44.37; H, 4.96; N, 7.39.

Found: C, 42.91; H, 4.80; N, 7.34.

5.5.3 Synthesis of [1-(N,N-Dimethylaminopropyl)-3-methylimidazol-2-ylidene]chloro(η6-p-

cymene)ruthenium(II) Hexafluorophosphate Dimethyl Sulfoxide Solvate ([Ru(p-cymene)

(C–NMe2)Cl]PF6·1.5 DMSO, 18). A Schlenk flask was charged with silver(I) oxide (145 mg,

0.63 mmol) and the [Ru(p-cymene)Cl2]2 dimer (127 mg, 0.21 mmol) in dry acetonitrile (15 mL)

under molecular sieves (3 Å). In a separate Schlenk flask was charged with 1g (100 mg, 0.42

mmol) and anhydrous dimethyl sulfoxide (DMSO, 5 mL) under an argon atmosphere. The

DMSO solution containing the dissolved imidazolium salt was then added to the stirring solution

of silver(I) oxide and the [Ru(p-cymene)Cl2]2 dimer in acetonitrile. Acetonitrile washing (5 mL)

was applied to the residual DMSO solution containing 1g, and this was also added to the reaction

mixture. This was stirred under an argon atmosphere at room temperature (25°C) for overnight.

After the reaction has gone to completion, the reaction mixture was filtered through a pad of

Celite under an argon atmosphere. The solvent was evaporated under reduced pressure. The

residue that obtained was dissolved in dichloromethane (10 mL) and this was added silver

hexafluorophosphate (105 mg, 0.42 mmol) and stirred further for 1 h. The suspension that

formed was filtered through a pad of Celite. The volume of solvent was reduced (2 mL), and

addition of diethyl ether (12 mL) to the dichloromethane solution yielded an orange-yellow oil.

The supernatant liquid was decanted and the residue was washed with diethyl ether (3 mL).

Trituration of the oil with diethyl ether (3 × 3 mL) afforded an orange powder which was

collected and dried in vacuo. Yield: 120 mg, 41%. 1H NMR (CD2Cl2, 253K, δ): 7.19 (d, JHH =

1.94 Hz, CH of imid., 1H), 7.16 (d, JHH = 1.96 Hz, CH of imid., 1H), 7.12 (d, JHH = 1.96 Hz, CH

of imid., 1H), 7.10 (d, JHH = 1.94 Hz, CH of imid., 1H), 5.63 (d, JHH = 6.03 Hz, Ar-CH of p-

cymene, 1H), 5.53-5.50 (m, Ar-CH of p-cymene, 2H), 5.44-5.41 (m, Ar-CH of p-cymene, 3H),

5.21 (m, Ar-CH of p-cymene, 2H), 4.43 (m, CH2, 2H), 4.26 (m, CH2, 4H), 3.91 (s, CH3, 3H),

3.82 (s, CH3, 3H), 3.10 (s, CH3 of DMSO, 3H), 3.00 (s, CH3 of N(CH3)2, 3H), 2.92 (s, CH3 of

147DMSO, 3H), 2.78 (m, CH of (CH3)2CH of p-cymene and CH2, 4H), 2.30 (m, CH2, 2H), 2.10 (s,

CH3 of N(CH3)2, 6H), 2.05 (m, CH2, 2H), 1.50 (s, CH3 of p-cymene, 3H), 1.25 (m, CH3 of

(CH3)2CH of p-cymene, CH3 of p-cymene and CH3 of N(CH3)2, 12H), 0.97 (d, JHH = 6.81 Hz,

CH3 of (CH3)2CH of p-cymene, 6H). 13C{1H} NMR (CD2Cl2, 253K, δ): 173.9, 170.8 (Ru–C),

125.4, 124.8, 124.6, 122.5 (Cimid.), 112.9, 112.2, 102.4, 99.5, 87.8, 87.0, 85.8, 85.2, 85.1, 83.7,

81.6, 80.3 (CAr-p-cymene), 60.9, 60.6 (CH3 of DMSO), 58.4, 50.0, 45.2, 43.3 (CH2), 39.4, 38.8

(CH3), 31.0 (CH of (CH3)2CH of p-cymene), 30.9 (CH3 of N(CH3)2), 30.5 (CH of (CH3)2CH of

p-cymene), 26.7, 26.4 (CH2), 24.2 (CH3 of p-cymene), 23.5 (CH3 of (CH3)2CH of p-cymene),

21.9 (CH3 of p-cymene), 21.6, 20.9, 19.2 (CH3 of (CH3)2CH of p-cymene), 18.0 (CH3 of

N(CH3)2). MS (ESI, methanol/water; m/z) 438.1 ([M]+), 402.1 ([M – Cl]+). Anal. Calcd for

C19H31ClF6N3PRu·1.5 C2H6SO: C, 37.74; H, 5.76; N, 6.00. Found: C, 37.11; H, 5.26; N, 6.62.

5.5.4 Catalysis. Oxygen-free tetrahydrofuran (THF) used for all of the catalytic runs was stirred

over sodium for 2-3 days under argon, and freshly distilled from sodium benzophenone ketyl

prior to use. Acetophenone was vacuum-distilled over phosphorus pentoxide (P2O5) and stored

under nitrogen prior to use. All of the other substrates were vacuum-distilled, dried over

activated molecular sieves, and stored under nitrogen prior to use. All of the H2-hydrogenation

reactions were performed at constant pressure using a stainless steel 50 mL Parr hydrogenation

reactor. The temperature was maintained at 50°C using a constant-temperature water bath. The

reactor was flushed several times with hydrogen gas at 2-4 bar prior to the addition of

catalyst/substrate and base solutions.

In a typical run (Table 5.2, entry 2), the catalyst 13 (3 mg, 5.0 μmol), benzophenone (181 mg,

0.99 mmol), and potassium tert-butoxide (5 mg, 0.044 mmol) were dissolved in THF (4 and

2mL, respectively) under a nitrogen atmosphere. The catalyst/substrate and base solutions were

taken up by means of two separate syringes and needles in a glovebox. The needles were

stoppered, and the syringes were taken to the reactor. The solutions were then injected into the

reactor against a flow of hydrogen gas. The hydrogen gas was adjusted to the desired pressure.

Small aliquots of the reaction mixture were quickly withdrawn with a syringe and needle under a

flow of hydrogen at timed intervals by venting the Parr reactor at reduced pressure.

Alternatively, small aliquots of the reaction mixture were sampled from a stainless steel

sampling dip tube attached to a modified Parr reactor. The dip tube was 30 cm in length with an

inner diameter of 0.01 in., and a swing valve was attached to the end of the sampling tube. Other

technical details were previously reported.9c Two small aliquots of samples were thereby

148withdrawn quickly at timed intervals by opening the swing valve, and the first two aliquots were

discarded. All samples for gas chromatography (GC) analyses were diluted to a total volume of

approximately 0.75 mL using oxygenated THF.

A Perkin-Elmer Clarus 400 chromatograph equipped with a chiral column (CP chirasil-Dex

CB 25 m × 2.5 mm) with an auto-sampling capability was used for GC analyses. Hydrogen was

used as a mobile phase at a column pressure of 5 psi with a split flow rate of 50 mL/min. The

injector temperature was 250°C and the FID temperature was 275°C. The oven temperatures and

the retention times (tR, tp, /min) for all of the substrates and alcohol products are given in the

Appendix. All of the conversions are reported as an average of two GC runs. The reported

conversions were reproducible.

5.5.5 Kinetics. A standard solution of the catalyst 13 (1.66 mM) was prepared by dissolving the

complex (25 mg) in THF (25 mL). Reaction mixtures were then prepared in THF by dispensing

the required amount of the catalyst and weighed amounts of acetophenone, phenylethanol, and

potassium tert-butoxide (or a standard solution of potassium tert-butoxide (17.8 mM) in THF for

base-dependent studies) and diluted to a total volume of 6 mL. The hydrogenation reaction and

sampling techniques were described as above in order to obtain at least five data points including

the origin (time = 0 min) at below 40% conversion to the product alcohol. The tabulated results

of initial rates with varying concentrations of catalyst, acetophenone, hydrogen, and potassium

tert-butoxide are given in Table 5.3. All of the conversions are reported as an average of at least

two GC runs. The reported conversions were reproducible.

5.5.6 Kinetic Isotope Effect Studies. D2 (99.8% D) gas and acetophenone-β,β,β-d3 (99% D)

were purchased from Cambridge Isotope Laboratories. Acetophenone-d3 was vacuum-distilled,

dried over activated molecular sieves, and stored under nitrogen prior to use. D2 gas was used as

received without further purification. For experiments using deuterium gas, the modified Parr

reactor with a stainless steel sampling dip tube was used. The reactor was degassed by

evacuation for 10 min, followed by refilling with 2-4 bar of deuterium gas. This was repeated

three times. The reaction mixtures were then injected into the reactor against a flow of deuterium

gas, and the gas pressure was adjusted to 8 bar. The tabulated results of the initial rates with

varying concentrations of acetophenone are given in the Table 5.4. Experiments using

acetophenone-d3 were conducted similarly to the kinetic studies described above.

1495.5.7 Computational Details. All density functional theory (DFT) calculations were performed

using the Gaussian0346 package with the restricted hybrid mPW1PW91functional.47 Ruthenium

was treated with the SDD48 relativistic effective core potential and an associated basis set. All

other atoms were treated with the double-ζ basis set 6-31++G**, which includes diffuse

functionals49 and additional p orbitals on hydrogen as well as additional d orbitals on carbon,

nitrogen, and oxygen.50 All geometry optimizations were conducted in the gas phase, and the

stationary points were characterized by normal mode analysis. Reported free energies were

obtained at 1 atm and 298 K using unscaled vibrational frequencies. The QST3 method was used

to locate transition states. All transition states reported were found to have a single imaginary

frequency. The calculated atomic polar tensor (APT) charges were used to reflect more

accurately the charge distribution on each atom under the derivative of dipole moments with

respect to an applied external electric field.51

46. Frisch, M. J., et al., Gaussian 03, Revision C.02 ed; Gaussian Inc.: Wallingford, CT 2004. Full citation is given in the Appendix.47. (a) Burke, K.; Perdew, J. P.; Wang, Y., Electronic Density Functional Theory: Recent Progress and New Directions; Plenum: New York, 1997; (b) Adamo, C.; Barone, V., J. Chem. Phys. 1998, 108, 664-675.48. (a) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H., Theor. Chim. Acta 1990, 77, 123-141; (b) Leininger, T.; Nicklass, A.; Stoll, H.; Dolg, M.; Schwerdtfeger, P., J. Chem. Phys. 1996, 105, 1052-1059.49. (a) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. V., J. Comput. Chem. 1983, 4, 294-301; (b) Lynch, B. J.; Zhao, Y.; Truhlar, D. G., J. Phys. Chem. A 2003, 107, 1384-1388.50. Frisch, M. J.; Pople, J. A.; Binkley, J. S., J. Chem. Phys. 1984, 80, 3265-3269.51. Cioslowski, J., J. Am. Chem. Soc. 1989, 111, 8333-8336.

150Chapter 6: Conventional Bifunctional Mechanism for Ketone

Hydrogenation Catalyzed by Structurally Similar Ruthenium and

Iridium Complexes but with Unconventional Intermediates for

Iridium

6.1 Abstract

An alcohol-assisted outer sphere bifunctional mechanism for the H2-hydrogenation of ketones

catalyzed by similar ruthenium and iridium systems is presented based on experimental and

theoretical evidence. The ruthenium(II) complex containing an N-heterocyclic carbene (NHC)

with a tethered primary amine donor (C–NH2), [RuCp*(C–NH2)py]PF6 (15, Cp* = pentamethyl-

cyclopentadienyl ligand, py = pyridine), when activated by an alkoxide base, has a higher

activity but with similar selectivity for the H2-hydrogenation of ketones in comparison to the

structurally similar iridium(III) complex, [IrCp*(C–NH2)Cl]PF6 (19). The presence of alcohol

accelerates catalysis in the ruthenium(II) system, and in the iridium(III) system but only when

the alkoxide base is used in large excess with respect to iridium. Computational studies using

density functional theory (DFT) methods reveal a higher free energy barrier for the cationic

iridium(III) system to transfer a proton/hydride couple from [MCp(C–NH2)H]n+ (M = Ir, n = 1;

Cp = cyclopentadienyl) to the ketone in an outer sphere bifunctional mechanism compared to the

neutral ruthenium(II) counterpart (M = Ru, n = 0). This supports an outer sphere bifunctional

mechanism for the ruthenium(II) system, but this is energetically unfavourable for the

iridium(III) counterpart. Consistent with this the iridium(III) hydride-amine complex, [IrCp*(C–

NH2)H]PF6 (21), was isolated and found to be inactive as a catalyst for ketone hydrogenation.

The cationic charge is thought to contribute to a diminished hydricity and reactivity of this metal

hydride. Nevertheless we present evidence that this iridium system, in the presence of excess

alkoxide base, does efficiently hydrogenate ketones via an outer sphere bifunctional mechanism

involving a novel, neutral hydride intermediate Ir(η4-Cp*H)(C–NH2)H. The formation of this

intermediate relies on the uncommon migration of a hydride ligand to the η5-Cp* ligand which

appears to be promoted by the unique NHC ligand of the present system. The important role of

the N-H group is illustrated by the poor catalytic activity of the structurally similar iridium(III)

complex, [IrCp*(C–NMe2) Cl]PF6 (22), which does not contain an N–H group. The carbonyl

151stretching wavenumber of the complexes [RuCp*(D–NH2)CO]X decreases as D is changed in the

order phosphine, NHC, 2'-pyridine, amine. This electronic effect results in the poorer

performance in the catalytic H2-hydrogenation of ketones of the phosphine complexes [RuCp*(P–

NH2)py]PF6 (16a) and [IrCp*(P–NH2)Cl]PF6 (20) compared to the more electron rich C–NH2

analogues.

6.2 Introduction

Catalytic hydrogenation of unsaturated bonds using dihydrogen is an attractive, atom

economical, chemical process.1 The activation of dihydrogen by homogenous catalysts is a

process of continuing interest.2 The use of an ancillary ligand such as an amido3 or an amine

donor,4 to heterolytically split dihydrogen has emerged as an effective strategy in the design of

catalysts for the hydrogenation of polar double bonds.5 This provides a bifunctional metal–

hydride and protic amine grouping for the efficient and selective reduction of organic molecules,

including ketones and imines, to produce valuable alcohols and amines.6 This idea has been

extended to the development of catalysts for C–C,6b, 7 C–O8 and C–N9 bond formation to provide

access to new synthetic building blocks which are otherwise difficult to synthesize using

conventional methods.10

1. (a) de Vries, J. G.; Elsevier, C. J., Eds, The Handbook of Homogeneous Hydrogenation, Wiley-VCH, Weinheim, Germany, 2004; Vol 1-3 ; (b) Kubas, G. J., Chem. Rev. 2007, 107, 4152-4205.2. (a) Samec, J. S. M.; Bäckvall, J. E.; Andersson, P. G.; Brandt, P., Chem. Soc. Rev. 2006, 35, 237-248; (b) Gloaguen, F.; Rauchfuss, T. B., Chem. Soc. Rev. 2009, 38, 100-108; (c) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J., Dalton Trans. 2009, 753-762; (d) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J., Chem. Rev. 2010, 110, 2294-2312.3. (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S., J. Org. Chem. 2001, 66, 7931-7944; (b) Ito, M.; Endo, Y.; Ikariya, T., Organometallics 2008, 27, 6053-6055; (c) Kuwata, S.; Ikariya, T., Dalton Trans. 2010, 39, 2984-2992.4. (a) Chu, H. S.; Lau, C. P.; Wong, K. Y.; Wong, W. T., Organometallics 1998, 17, 2768-2777; (b) Lee, D. H.; Patel, B. P.; Clot, E.; Eisenstein, O.; Crabtree, R. H., Chem. Commun. 1999, 297-298; (c) Ayllon, J. A.; Sayers, S. F.; Sabo-Etienne, S.; Donnadieu, B.; Chaudret, B.; Clot, E., Organometallics 1999, 18, 3981-3990; (d) Henry, R. M.; Shoemaker, R. K.; DuBois, D. L.; DuBois, M. R., J. Am Chem Soc. 2006, 128, 3002-3010; (e) Grützmacher, H., Angew. Chem. Int. Ed. 2008, 47, 1814-1818; (f) Kayaki, Y.; Ikeda, H.; Tsurumaki, J. I.; Shimizu, I.; Yamamoto, A., Bull. Chem. Soc. Jpn. 2008, 81, 1053-1061.5. (a) Jessop, P. G.; Morris, R. H., Coord. Chem. Rev. 1992, 121, 155-284; (b) Morris, R. H., Can. J. Chem. 1996, 74, 1907-1915; (c) Clapham, S. E.; Hadzovic, A.; Morris, R. H., Coord. Chem. Rev. 2004, 248, 2201-2237; (d) DuBois, M. R.; DuBois, D. L., Chem. Soc. Rev. 2009, 38, 62-72.6. (a) Muniz, K., Angew. Chem. Int. Ed. 2005, 44, 6622-6627; (b) Ikariya, T.; Murata, K.; Noyori, R., Org. Biomol. Chem. 2006, 4, 393-406; (c) Ito, M.; Ikariya, T., Chem. Commun. 2007, 5134-5142.7. (a) Guo, R.; Morris, R. H.; Song, D., J. Am. Chem. Soc. 2005, 127, 516-517; (b) Gridnev, I. D.; Watanabe, M.; Wang, H.; Ikariya, T., J. Am. Chem. Soc. 2010, 132, 16637-16650; (c) Ikariya, T.; Gridnev, I. D., Top. Catal. 2010, 53, 894-901.8. (a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D., J. Am. Chem. Soc. 2005, 127, 10840-10841; (b) Zweifel, T.; Naubron, J. V.; Grützmacher, H., Angew. Chem. Int. Ed. 2009, 48, 559-563.

152The “NH effect”, which involves the bifunctional action of M–H/N–H groups to attack a polar

bond in the outer coordination sphere, has been studied the most both experimentally11 and

theoretically.12 The ketone hydrogenation is proposed to proceed via a six-membered pericyclic

transition state involving hydrogen bonding of the N-H group with the oxygen of the ketone and

attack of the carbonyl group by the metal hydride.3a, 5c Many research groups,12e, 13 including

ours,12l, 14 have shown that the heterolytic splitting of a coordinated η2-H2 ligand is rate

determining.12d, 12e, 12h, 12i, 12k-m, 13-15 The key intermediates of the catalytic cycle involving the trans-

dihydride-amine and the monohydrido-amido catalysts of RuXY(diamine)(phosphine)2 type

systems (X = H, Cl; Y = H, BH4, H, OR) have been identified and isolated.14, 16 Ruthenium(II)

alkoxide complexes have been observed at low temperature prior to the formation of an amido

species17 and one of these has been recently isolated.18 Under optimum conditions, such catalysts

allow hydrogenation to occur under mild conditions: room temperature, low hydrogen pressures

with no added base.14, 16a, 19 The importance of the N-H group was demonstrated by the fact that

systems containing only a metal hydride were found to be less active and selective and required

forcing conditions in the hydrogenation of ketones.20 However, the N–H group is not needed for

the hydrogenation of β-keto-esters which chelate to the metal center.21

9. (a) Gunanathan, C.; Ben-David, Y.; Milstein, D., Science 2007, 317, 790-792; (b) Gnanaprakasam, B.; Milstein, D., J. Am. Chem. Soc. 2011, 133, 1682-1685.10. Milstein, D., Top. Catal. 2010, 53, 915-923 and references therein.11. (a) Rosales, M., Coord. Chem. Rev. 2000, 196, 249-280; (b) Maire, P.; Buttner, T.; Breher, F.; Le Floch, P.; Grützmacher, H., Angew. Chem. Int. Ed. 2005, 44, 6318-6323; (c) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C.; Noyori, R., J. Am. Chem. Soc. 2006, 128, 8724-8725; (d) Kass, M.; Friedrich, A.; Drees, M.; Schneider, S., Angew. Chem. Int. Ed. 2009, 48, 905-907; (e) Friedrich, A.; Drees, M.; auf der Gunne, J. S.; Schneider, S., J. Am. Chem. Soc. 2009, 131, 17552-17553; (f) Cheung, F. K.; Clarke, A. J.; Clarkson, G. J.; Fox, D. J.; Graham, M. A.; Lin, C. X.; Criville, A. L.; Wills, M., Dalton Trans. 2010, 39, 1395-1402; (g) Picot, A.; Dyer, H.; Buchard, A.; Auffrant, A.; Vendier, L.; Le Floch, P.; Sabo-Etienne, S., Inorg. Chem. 2010, 49, 1310-1312; (h) Bertoli, M.; Choualeb, A.; Gusev, D. G.; Lough, A. J.; Major, Q.; Moore, B., Dalton Trans. 2011, 40, 8941-8949.12. (a) Alonso, D. A.; Brandt, P.; Nordin, S. J. M.; Andersson, P. G., J. Am. Chem. Soc. 1999, 121, 9580-9588; (b) Petra, D. G. I.; Reek, J. N. H.; Handgraaf, J. W.; Meijer, E. J.; Dierkes, P.; Kamer, P. C. J.; Brussee, J.; Schoemaker, H. E.; van Leeuwen, P., Chem. Eur. J. 2000, 6, 2818-2829; (c) Yamakawa, M.; Ito, H.; Noyori, R., J. Am. Chem. Soc. 2000, 122, 1466-1478; (d) Handgraaf, J. W.; Reek, J. N. H.; Meijer, E. J., Organometallics 2003, 22, 3150-3157; (e) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G., J. Am. Chem. Soc. 2005, 127, 15083-15090; (f) Handgraaf, J. W.; Meijer, E. J., J. Am. Chem. Soc. 2007, 129, 3099-3103; (g) Comas-Vives, A.; Ujaque, G.; Lledos, A., Organometallics 2007, 26, 4135-4144; (h) Di Tommaso, D.; French, S. A.; Catlow, C. R. A., J. Mol. Struct. (THEOCHEM) 2007, 812, 39-49; (i) Puchta, R.; Dahlenburg, L.; Clark, T., Chem. Eur. J. 2008, 14, 8898-8903; (j) Chen, Y.; Liu, S. B.; Lei, M., J. Phys. Chem. C 2008, 112, 13524-13527; (k) Chen, Y.; Tang, Y. H.; Lei, M., Dalton Trans. 2009, 2359-2364; (l) Zimmer-De Iuliis, M.; Morris, R. H., J. Am. Chem. Soc. 2009, 131, 11263-11269; (m) Lei, M.; Zhang, W. C.; Chen, Y.; Tang, Y. H., Organometallics 2010, 29, 543-548; (n) Li, H. X.; Lu, G.; Jiang, J. L.; Huang, F.; Wang, Z. X., Organometallics 2011, 30, 2349-2363.13. (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R., J. Am. Chem. Soc. 2003, 125, 13490-13503; (b) Hamilton, R. J.; Leong, C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H., J. Am. Chem. Soc. 2005, 127, 4152-4153; (c) Sandoval, C. A.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Noyori, R., Chem. Asian J. 2006, 1, 102-110.

153The effect of alcohol in bifunctional catalysis using the “NH effect” has also been well

studied. Combined computational and experimental studies on many systems have shown that

the presence of alcohol in catalysis plays an active role to serve as a proton shuttle that assists in

the heterolytic splitting of the η2-H2 ligand. 6c, 12e, 13a, 14b, 19b, 20b, 22 This decreases the energy barrier

for the activation of H2 but does not significantly change the energy barrier for the transfer of a

proton/hydride couple to the ketone in a hydrogen-bonded network.12e, 19b

Certain ruthenium(II) complexes bearing a phosphine–amine (P–NH2) ligand, including the

complexes trans-Ru(H)2((S)-BINAP)(P–NH2)23 and RuCp*(κ2(P,N)-PPh2CH2CH2NH2)H24

(Figure 6.1) catalyze efficiently the hydrogenation of a variety of polar bonds including those of

ketones,20h, 23, 25 imines,16b esters and lactones,26 epoxides24 and cyclic imides.27 The notion of

replacing a phosphine with a more electron-donating N-heterocyclic carbene (NHC) donor is

attractive with the promise of a reduction in the toxicity of catalyst precursors and contaminants

in the hydrogenated products leading to greener catalysis.28 Thus, the replacement of phosphine

by an NHC donor would give a donor-functionalized NHC29 containing an NHC ligand and a

14. (a) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2002, 124, 15104-15118; (b) Rautenstrauch, V.; Hoang-Cong, X.; Churlaud, R.; Abdur-Rashid, K.; Morris, R. H., Chem. Eur. J. 2003, 9, 4954-4967.15. Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2005, 127, 1870-1882.16. (a) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2001, 123, 7473-7474; (b) Abdur-Rashid, K.; Guo, R. W.; Lough, A. J.; Morris, R. H.; Song, D. T., Adv. Synth. Catal. 2005, 347, 571-579.17. (a) Hamilton, R. J.; Bergens, S. H., J. Am. Chem. Soc. 2008, 130, 11979-11987; (b) Takebayashi, S.; Dabral, N.; Miskolzie, M.; Bergens, S. H., J. Am. Chem. Soc. 2011, 133, 9666-9669.18. Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.; Gusev, D. G., Organometallics 2011, 30, 3479-3482 19. (a) Clapham, S. E.; Morris, R. H., Organometallics 2005, 24, 479-481; (b) Hadzovic, A.; Song, D.; MacLaughlin, C. M.; Morris, R. H., Organometallics 2007, 26, 5987-5999.20. (a) Standfest-Hauser, C.; Slugovc, C.; Mereiter, K.; Schmid, R.; Kirchner, K.; Xiao, L.; Weissensteiner, W., Dalton Trans. 2001, 2989-2995; (b) Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T., Organometallics 2001, 20, 379-381; (c) Leong, C. G.; Akotsi, O. M.; Ferguson, M. J.; Bergens, S. H., Chem. Commun. 2003, 750-751; (d) Lundgren, R. J.; Rankin, M. A.; McDonald, R.; Schatte, G.; Stradiotto, M., Angew. Chem. Int. Ed. 2007, 46, 4732-4735; (e) Ma, G. B.; McDonald, R.; Ferguson, M.; Cavell, R. G.; Patrick, B. O.; James, B. R.; Hu, T. Q., Organometallics 2007, 26, 846-854; (f) Baratta, W.; Ballico, M.; Esposito, G.; Rigo, P., Chem. Eur. J. 2008, 14, 5588-5595; (g) Sandoval, C. A.; Shi, Q. X.; Liu, S. S.; Noyori, R., Chem. Asian J. 2009, 4, 1221-1224; (h) Phillips, S. D.; Fuentes, J. A.; Clarke, M. L., Chem. Eur. J. 2010, 16, 8002-8005; (i) Soni, R.; Cheung, F. K.; Clarkson, G. C.; Martins, J. E. D.; Graham, M. A.; Wills, M., Org. Biomol. Chem. 2011, 9, 3290-3294.21. (a) Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S., J. Am. Chem. Soc. 1987, 109, 5856-5858; (b) Daley, C. J. A.; Wiles, J. A.; Bergens, S. H., Can. J. Chem. 1998, 76, 1447-1456; (c) Noyori, R.; Ohkuma, T., Angew. Chem. Int. Ed. 2001, 40, 40-73; (d) Daley, C. J. A.; Bergens, S. H., J. Am. Chem. Soc. 2002, 124, 3680-3691.22. (a) Casey, C. P.; Johnson, J. B.; Singer, S. W.; Cui, Q., J. Am. Chem. Soc. 2005, 127, 3100-3109; (b) Heiden, Z. M.; Rauchfuss, T. B., J. Am. Chem. Soc. 2009, 131, 3593-3600; (c) Casey, C. P.; Johnson, J. B.; Jiao, X. D.; Beetner, S. E.; Singer, S. W., Chem. Commun. 2010, 46, 7915-7917.

154primary amine donor (C–NH2). Douthwaite and co-workers reported the synthesis of the first

palladium complex containing such a C–NH2 ligand (Figure 6.1).30

Figure 6.1. Late transition metal complexes containing a chelating N-heterocyclic carbene

(NHC)-primary amine (C–NH2) or a chelating phosphine-primary amine (P–NH2) ligand.

We then began to explore the use of a more conveniently prepared C–NH2 ligand in metal

complexes for the catalytic hydrogenation of ketones using H2 or 2-propanol as the hydrogen

source. The complexes [M(p-cymene)(C–NH2)Cl]PF6 (13, M = Ru;31 14, M = Os,32 Figure 6.1),

were prepared by the transmetalation reaction31 of a nickel(II) complex, [Ni(C–NH2)2](PF6)2 (12,

Figure 6.1 and see Chapter 4), with the appropriate precursor complex. The hydride-amine

complex, [Ru(p-cymene)(C–NH2)H]PF6 (17, see Chapter 5), was prepared, but this failed to

transfer its proton/hydride couple to acetophenone in either stoichiometric or catalytic reactions.

Experimental and computational studies suggested that an outer sphere bifunctional mechanism

23. Guo, R.; Lough, A. J.; Morris, R. H.; Song, D., Organometallics 2004, 23, 5524-5529.24. Ito, M.; Hirakawa, M.; Osaku, A.; Ikariya, T., Organometallics 2003, 22, 4190-4192.25. Jia, W. L.; Chen, X. H.; Guo, R. W.; Sui-Seng, C.; Amoroso, D.; Lough, A. J.; Abdur-Rashid, K., Dalton Trans. 2009, 8301-8307.26. (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P., Angew. Chem. Int. Ed. 2007, 46, 7473-7476; (b) Clarke, M. L.; Diaz-Valenzuela, M. B.; Slawin, A. M. Z., Organometallics 2007, 26, 16-19; (c) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saito, T., Adv. Synth. Catal. 2010, 352, 92-96.27. (a) Ito, M.; Sakaguchi, A.; Kobayashi, C.; Ikariya, T., J. Am. Chem. Soc. 2007, 129, 290-291; (b) Ito, M.; Kobayashi, C.; Himizu, A.; Ikariya, T., J. Am. Chem. Soc. 2010, 132, 11414-11415.28. (a) Lee, H. M.; Lee, C. C.; Cheng, P. Y., Curr. Org. Chem. 2007, 11, 1491-1524; (b) Hahn, F. E.; Jahnke, M. C., Angew. Chem. Int. Ed. 2008, 47, 3122-3172; (c) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P., Chem. Rev. 2009, 109, 3612-3676.29. (a) Normand, A. T.; Cavell, K. J., Eur. J. Inorg. Chem. 2008, 2781-2800; (b) Corberan, R.; Mas-Marza, E.; Peris, E., Eur. J. Inorg. Chem. 2009, 1700-1716.30. Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R.; Houghton, J.; Kariuki, B. M.; Simonovic, S., Dalton Trans. 2004, 3528-3535.31. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2009, 28, 6755-6761.32. O, W. W. N.; Lough, A. J.; Morris, R. H., Organometallics 2011, 30, 1236-1252.

RuCl NNN

CH3

HH

NiN

NN N

NN

H3CCH3

2+

(PF6)2

H H H H

PF6

Ru

N PPh2HHH

Ru

NN

N

CH3 PF6NHH

Ikariya

12

15

N

NPh

nPr

NPd

ClClHH

Douthwaite 13

Ru

H

HN

Ph2P

CH3

Ph

H H

PPh2

Ph2P

t rans-Ru(H)2((S)-BINAP)(P-NH2)

+

+

155was not viable for this cationic hydride-amine complex, and that an inner sphere mechanism

involving the decoordination of the primary amine group was more likely to occur (Figure 6.2).32

Figure 6.2. An inner sphere mechanism involving the decoordination of the primary amine

group proposed for the H2-hydrogenation of ketones catalyzed by complex 13 in the presence of

an alkoxide base.

Although there are many metal complexes containing an amine-functionalized NHC ligand,30,

33 none were reported to be useful for ketone hydrogenation33c, 33f apart from our work.34 We have

prepared the ruthenium(II) complex, [RuCp*(C–NH2)py]PF6 (15, Cp* = pentamethyl-

cyclopentadienyl ligand; py = pyridine, Figure 6.1) and found it to be very active for the

hydrogenation of a variety of ketones, styrene oxide, an aromatic ester and a ketimine with high

substrate to catalyst loadings under very mild reaction conditions (8 bar of H2 pressure, 25°C): a

maximum turnover frequency (TOF) of 17300 h-1 is achieved with this catalyst in the H2-

hydrogenation of acetophenone in 2-propanol.34 This system has activity that is superior to the

related catalysts, RuCp*(κ2(P,N)-PPh2CH2CH2NH2)Cl (16b), and RuCp*(diamine)Cl.12e, 20b, 24

In the current study35 we show that when 15 is activated by an alkoxide base, it follows an

alcohol-assisted outer sphere bifunctional mechanism in the H2-hydrogenation of ketones

involving the action of a metal hydride and a protic amine group. To our surprise, a structurally

similar iridium(III) complex when it is activated with an excess of alkoxide base in 2-propanol,

33. (a) Arnold, P. L.; Mungur, S. A.; Blake, A. J.; Wilson, C., Angew. Chem. Int. Ed. 2003, 42, 5981-5984; (b) Douthwaite, R. E.; Houghton, J.; Kariuki, B. M., Chem. Commun. 2004, 698-699; (c) Jong, H.; Patrick, B. O.; Fryzuk, M. D., Can. J. Chem. 2008, 86, 803-810; (d) Wei, W.; Qin, Y.; Luo, M.; Xia, P.; Wong, M. S., Organometallics 2008, 27, 2268-2272; (e) Arnold, P. L.; McMaster, J.; Liddle, S. T., Chem. Commun. 2009, 818-820; (f) Dyson, G.; Frison, J. C.; Whitwood, A. C.; Douthwaite, R. E., Dalton Trans. 2009, 7141-7151; (g) Cross, W. B.; Daly, C. G.; Ackerman, R. L.; George, I. R.; Singh, K., Dalton Trans. 2011, 40, 495-505; (h) Jong, H.; Patrick, B. O.; Fryzuk, M. D., Organometallics 2011, 30, 2333-2341.34. O, W. W. N.; Lough, A. J.; Morris, R. H., Chem. Commun. 2010, 46, 8240 - 8242.35. O, W. W. N.; Lough, A. J.; Morris, R. H., Submitted 2011.

OR

HOR

H

Inner Sphere

H2

CH3NN

RuNH

H HO

R'

R

+

156likely undergoes the same mechanism involving iridium(I) intermediates (Scheme 6.1). Herein,

we will present both experimental and theoretical evidences to support the two elementary steps

in the alcohol-assisted outer sphere bifunctional mechanism: a) the heterolytic splitting of

dihydrogen at the active metal center, aided by a 2-propanol molecule acting as an proton shuttle

(Step A in Scheme 6.1); b) the transfer of an M–H/N–H couple to the ketone in the outer sphere

(Step B in Scheme 6.1). Other possible mechanisms including a hydride attack on a coordinated

ketone in the inner coordination sphere will be described briefly. Of note, diagonal relationships

between late transition metals were studied for the dihydrogen complexes [M(η2-

H2)2(H)2(PCy3)]n+ (M = Ru, n = 0; M = Ir, n = 1),36 and more recently their use in the activation

of B–H bonds.37 Also relevant to the current work is a computational study of the transfer

hydrogenation of ketones catalyzed by structurally similar ruthenium(II) and iridium(I)

systems.12d In addition, a comparison between the C–NH2 and analogous P–NH2 ligand in

ruthenium(II) and iridium(III) catalysts allows us to evaluate the relative merits of these ligands

in the homogenous hydrogenation of ketones.

Scheme 6.1. An Alcohol-assisted Outer Sphere Bifunctional Mechanism of H2-Hydrogenation of

Ketones Catalyzed by Ruthenium(II) and Iridium(I) Systems Containing a C–NH2 Ligand.

36. (a) Crabtree, R. H.; Lavin, M.; Bonneviot, L., J. Am. Chem. Soc. 1986, 108, 4032-4037; (b) Arliguie, T.; Chaudret, B.; Morris, R. H.; Sella, A., Inorg. Chem. 1988, 27, 598-599.37. Alcaraz, G.; Chaplin, A. B.; Stevens, C. J.; Clot, E.; Vendier, L.; Weller, A. S.; Sabo-Etienne, S., Organometallics 2010, 29, 5591-5595.

M NNN

CH3

H

MH NNN

CH3

HH

H2

OR'

OHH

R'

M NNN

CH3

H

HH

MH NNN

CH3

HH

O

R'

RR

R

O HH

OHH

OHH

OH

HAlcohol-Assisted Outer Sphere

Bifunctional Mechanism

M = Ru,

H

= η 5-

= η 4-M = Ir,

Step A

Step B


6.3.1 Synthesis of Ruthenium(II) and Iridium(III) Complexes Containing a C–NH2 Ligand.

The ruthenium(II) complex, [RuCp*(C–NH2)py]PF6 (15), was prepared by a transmetalation

reaction31, 34 of 12 and RuCp*(cod)Cl in refluxing acetonitrile followed by the addition of pyridine

in tetrahydrofuran (THF, Scheme 6.2). The characterization of this complex has been described

in Chapter 4.34 The structurally similar iridium(III) complex was thereby synthesized similarly

using 1231, 34 and [IrCp*Cl2]2 in refluxing acetonitrile. This afforded the complex, [IrCp*(C–

NH2)Cl]PF6 (19), as an air stable yellow powder upon isolation (Scheme 6.2). The solid state

structure of 19 has a piano-stool geometry at the iridium center with coordinated Cp*, C–NH2

and chloride ligands (Figure 6.3). The Ir–Ccarbene distance and the Ir–Ccarbene resonance in its 13C{1H} NMR spectrum are typical of most iridium(III) complexes containing an NHC ligand.38

To compare the donor strength properties of a phosphine with an N-heterocyclic carbene, the

diphenylphosphino-containing complex [IrCp*(P–NH2)Cl]PF6 (20, (P–NH2 = 2-(diphenyl-

phosphino)benzylamine herein, Scheme 6.3 and Figure 6.4) was prepared and has been

structurally characterized. The ruthenium(II) analogue (complex 16a) was previously described

in Chapter 4.34

Scheme 6.2. Synthesis of Iridium(III) and Ruthenium(II) Complexes Containing a C–NH2

Ligand.

NiN

NN N

NN

H3CCH3

2+

(PF6)2

H H H H

12

THF, rtCO (1 atm)

Ru

NN

N

CH3 PF6OCHH

23

1) 1.5 RuCp*(cod)Cl∆ , CH3CN

Ru

NN

N

CH3 PF6N

HH

15

2) pyridine, THF, rt

[IrCp*Cl2]2 ∆ , CH3CN

Ir

NN

N

CH3 PF6Cl2HH

19

1.5

1.5

Ir

NN

N

CH3 PF6H2HH

iPrOH, 50°C

6 NaOiPr

+

+

+

+

21

158Scheme 6.3. Synthesis of Iridium(III) and Ruthenium(II) Complexes Containing a P–NH2

Ligand.


counteranion and most of the hydrogens have been omitted for clarity. Selected bond distances

(Å) and bond angles (deg): Ir(1)–C(1), 2.067(7); Ir(1)–N(3), 2.127(5); Ir(1)–Cl(1), 2.424(2);

Ir(1)–C(13), 2.199(6); C(1)–Ir(1)–N(3), 90.9(2); C(1)–Ir(1)–Cl(1), 92.2(2); Cl(1)–Ir(1)–N(3),

80.7(1).

38. (a) Albrecht, M.; Miecznikowski, J. R.; Samuel, A.; Faller, J. W.; Crabtree, R. H., Organometallics 2002, 21, 3596-3604; (b) Hanasaka, F.; Fujita, K.; Yamaguchi, R., Organometallics 2005, 24, 3422-3433; (c) Hanasaka, F.; Fujita, K.-i.; Yamaguchi, R., Organometallics 2006, 25, 4643-4647; (d) Corberán, R.; Sanaú, M.; Peris, E., Organometallics 2007, 26, 3492-3498; (e) da Costa, A. P.; Viciano, M.; Sanau, M.; Merino, S.; Tejeda, J.; Peris, E.; Royo, B., Organometallics 2008, 27, 1305-1309; (f) Corberan, R.; Peris, E., Organometallics 2008, 27, 1954-1958; (g) da Costa, A. P.; Sanau, M.; Peris, E.; Royo, B., Dalton Trans. 2009, 6960-6966; (h) Gnanamgari, D.; Sauer, E. L. O.; Schley, N. D.; Butler, C.; Incarvito, C. D.; Crabtree, R. H., Organometallics 2009, 28, 321-325.

NH2 PPh2 RuPPh2N

PF6OCCH2Cl2, rt H

H

20

RuCp*(cod)Cl

2) CO (1 atm), THF, rt

1) AgPF6, CH3CN, rt

IrPPh2N

PF6Cl

CH2Cl2, rt

HH

24

0.5 [IrCp*Cl2]2

AgPF6CH3CN, rt

+

+

159



(Å) and bond angles (deg): Ir(1)–P(1), 2.307(2); Ir(1)–N(1), 2.146(8); Ir(1)–Cl(1), 2.407(2);

Ir(1)–C(24), 2.208(9); P(1)–Ir(1)–N(1), 88.9(2); P(1)–Ir(1)–Cl(1), 89.02(9); Cl(1)–Ir(1)–N(1),

82.3(2).

6.3.2 Synthesis, Observation, and Reactivity of Hydride Complexes of Ruthenium(II) and

Iridium(III). Hydride intermediates have been proposed in the catalytic cycles for the

hydrogenation of polar bonds and the racemization of chiral alcohols. The complex,

RuCp*(κ2(P,N)-PPh2CH2CH2NH2)H, which was suggested to be present during the catalytic

hydrogenolysis of epoxides, has been observed but not isolated.24 Hydride intermediates have

been observed spectroscopically in the racemization catalyst system containing Ru(η5-Cp*)

(ICy)Cl, NaOtBu and (S)-1-phenylethanol (ICy = 1,3-dicyclohexylimidazol-2-ylidene).39 The

complex, Ru(η5-C5Ph5)(CO)2H, has been isolated and this catalyzes the racemization of (S)-1-

phenylethanol40 via an inner sphere mechanism upon the dissociation of the carbonyl ligand.41

In order to provide evidence to support an alcohol-assisted outer sphere bifunctional

mechanism, we sought to observe or isolate the hydride-amine complex, [MCp*(C–NH2)H]n+ (M

= Ru, n = 0; M = Ir, n = 1), which can potentially transfer a proton/hydride couple from its M–

H/N–H group to the ketone (Step B in Scheme 6.1).3a, 6b, 6c Attempts to isolate such a complex for

the ruthenium(II) system were not successful. Reactions of excess or stoichiometric amounts of 39. Bosson, J.; Poater, A.; Cavallo, L.; Nolan, S. P., J. Am. Chem. Soc. 2010, 132, 13146-13149.

40. Martín-Matute, B.; Edin, M.; Bogár, K.; Kaynak, F. B.; Bäckvall, J. E., J. Am. Chem. Soc. 2005, 127, 8817-8825.41. Warner, M. C.; Verho, O.; Backvall, J. E., J. Am. Chem. Soc. 2011, 133, 2820-2823.

160base (potassium tert-butoxide (KOtBu), NaOiPr, NaOMe, NaBH4, KOH, KH or K-Selectride)

with complex 15 in THF under a hydrogen atmosphere (up to 8 bar) or in 2-propanol solution

gave intractable products. Nevertheless, a hydride peak was observed at -9.23 ppm in THF-d8

when the reaction was carried out under a hydrogen atmosphere in the presence of KOtBu.

Attempts to utilize such reaction mixture upon removal of excess KOtBu in the catalytic

hydrogenation of acetophenone (0.15 or 1.9 M) using 8 bar of H2 pressure at 25°C in the absence

of base gave no conversion to the product alcohol.

However, reactions of complex 15 with sodium 2-propoxide (2.6 equiv.) or potassium 1-

phenylethoxide (1.3 equiv.) in THF-d8 at 25°C under argon gave a species containing a new

hydride peak at -9.47 ppm. The relative integration of this peak against the alkoxide suggested

that 6% of the starting material was converted to this hydride. A hydride peak at -9.23 ppm was

also observed in a smaller amount in these two experiments. Acetone and acetophenone that

were produced from β-hydride elimination of the alkoxides were observed as well with 2% and

8% conversion, respectively. After leaving the solutions for 1 day in sealed NMR tubes at 25°C,

the hydride peaks disappeared and both samples contained less than 2% of the ketone. These

results suggest that the hydride-containing species at -9.47 ppm in THF-d8 may represent the true

catalytically active species, instead of the one that was observed at -9.23 ppm. These hydride

complexes, however, are difficult to identify due to the complexity of the reaction mixture and

their high reactivity.

The iridium(III) hydride-amine complex [IrCp*(C–NH2)H]PF6 (21), on the other hand, was

successfully prepared from a warm 2-propanol solution of 19 containing three equiv. of sodium

2-propoxide. The analytically pure compound can be isolated in moderate yields (Scheme 6.2).

In determining its solid state structure (Figure 6.5), the hydride position in the piano-stool

complex was not refined but instead was located approximately by use of an electron density

difference map.35 The Ir–H distance was thus determined to be 1.54 Å, which is typical of

iridium hydride complexes containing a Cp* ligand.42 The Ir–Ccarbene distance for 21 (2.015(5) Å)

is shorter than that of 19 (2.067(7) Å). The Ir–Ccarbene and Ir–H resonances of 21 in acetonitrile-d3

were observed at 157.0 and -13.59 ppm in the 13C{1H} and 1H NMR spectra, respectively. The

characteristic Ir–H stretch was observed at 2068 cm-1 in the infrared spectrum.

42. (a) Buchanan, J. M.; Stryker, J. M.; Bergman, R. G., J. Am. Chem. Soc. 1986, 108, 1537-1550; (b) Glueck, D. S.; Winslow, L. J. N.; Bergman, R. G., Organometallics 1991, 10, 1462-1479; (c) Ohki, Y.; Sakamoto, M.; Tatsumi, K., J. Am. Chem. Soc. 2008, 130, 11610-11611.

161


counteranion and most of the hydrogens have been omitted for clarity. The position of the

hydride ligand is not refined and thus not shown. Selected bond distances (Å) and bond angles

(deg): Ir(1)–C(1), 2.015(5); Ir(1)–N(3), 2.151(4); Ir(1)–C(14), 2.233(3); C(1)–Ir(1)–N(3),

89.6(2).

The bifunctional Ir–H and N–H groups of the hydride-amine complex 21 should react with a

polar double bond if it is truly an intermediate of the outer sphere mechanism that utilizes the

“NH effect”. This was tested in a stoichiometric reaction. The reaction mixture of 21 and

acetophenone in THF-d8 when heated at 50°C did not result in any product alcohol. The addition

of 1.5 to 2 equiv. of KOtBu prior to or after the addition of acetophenone to 21 in THF-d8 did not

give the reduced product. It appears that metal hydride is not hydridic enough and therefore not

reactive towards the polar double bond, in line with the properties of the cationic complex [Ru(p-

cymene)(C–NH2)H]PF6 (17) that we have isolated.32 Crabtree and co-workers have isolated an

iridium(III) complex, [Ir(η5-HOC5H4)(PPh3)2H]BF4¸which failed to react with aldehydes.43

Attempts to observe an iridium(III) dihydrogen complex [IrCp*(C–NH2)(η2-H2)]2+ similar to the

bis-NHC complex [IrCp*(C–C)(η2-H2)]2+ 44 and measure its pKa value by equilibrating known

amounts of 21, the phosphonium salts [HPCy3]BPh4 (pKαTHF

= 9.7)45 or [HPtBu3]BPh4 (pKαTHF

=

10.6)45 in THF-d8 were not successful due to the facile displacement of the coordinated

43. Li, X. W.; Chen, P.; Faller, J. W.; Crabtree, R. H., Organometallics 2005, 24, 4810-4815.44. Vogt, M.; Pons, V.; Heinekey, D. M., Organometallics 2005, 24, 1832-1836.45. Abdur-Rashid, K.; Fong, T. P.; Greaves, B.; Gusev, D. G.; Hinman, J. G.; Landau, S. E.; Lough, A. J.; Morris, R. H., J. Am. Chem. Soc. 2000, 122, 9155-9171.

162dihydrogen by the phosphine that forms. We conclude that complex 21 is unlikely to be an active

species involved in step B of the alcohol-assisted outer sphere bifunctional mechanism (Scheme

6.1).

6.3.3 Synthesis of an Iridium(III) Complex Containing a C–NMe2 Ligand. The importance of

the N–H group in the outer sphere bifunctional catalysis involving the action of M–H/N–H (Step

B in Scheme 6.1) has been demonstrated for several catalysts.20b, 20f-i, 32 However, there are active

systems for the hydrogenation of ketones that lack the N–H group; these, in most cases, operate

by an inner sphere mechanism which involves the coordination of the ketone to the metal

center.20a, 20c-e We attempted to address this issue by the preparation of an analogous iridium(III)

complex with an N-heterocyclic carbene containing a tethered tertiary amine donor (C–NMe2).

When chelated, this ligand forms a seven-membered ring including the metal center. The desired

complex was synthesized in one pot in two steps, by first the in situ generation of a silver(I)

complex containing the C–NMe2 ligand from the reaction of silver(I) oxide and 1-(N,N-

dimethylamino)propyl-3-methylimidazolium chloride hydrochloride (HC–NMe2·HCl, 1g),46 and

the C–NMe2 ligand was transmetalated from silver(I) to [IrCp*Cl2]2 in the same pot in the second

step (Scheme 6.4).32, 47 A salt metathesis reaction with AgPF6 afforded a pale yellow powder

upon isolation, which was identified as [IrCp*(C–NMe2)Cl]PF6 (22) by NMR spectroscopy and

an X-ray diffraction study (Figure 6.6). In comparison to 19, the piano-stool complex has a

shorter Ir–Ccarbene distance (19: 2.067(7)Å, 22: 2.036(4)Å), a longer Ir–N distance (19: 2.127(5)Å,

22: 2.225(4)Å) and a smaller C(1)–Ir(1)–N(3) bite angle of the chelate (19: 90.9(2)o, 22:

87.5(2)o), otherwise it has similar NMR spectroscopic properties to those of other iridium(III)

complexes containing an NHC ligand.38c

Scheme 6.4. Synthesis of an Iridium(III) Complex Containing a C–NMe2 ligand.

46. Jimenez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Gierz, V.; Lahoz, F. J.; Oro, L. A., Organometallics 2008, 27, 224-234.47. Warsink, S.; de Boer, S. Y.; Jongens, L. M.; Fu, C. F.; Liu, S. T.; Chen, J. T.; Lutz, M.; Spek, A. L.; Elsevier, C. J., Dalton Trans. 2009, 7080-7086.

0.5 [IrCp*Cl2]2DMSO:CH3CN (1:4), rt

N NCH3 N HCl1.5 Ag2O

AgPF6

CH3CN:CH2Cl2 (1:1), rt

1g

Ir

NN

N

CH3 PF6Cl

22

+

163



(Å) and bond angles (deg): Ir(1)–C(1), 2.036(4); Ir(1)–N(3), 2.225(4); Ir(1)–Cl(1), 2.426(1);

Ir(1)–C(11), 2.264(4); C(1)–Ir(1)–N(3), 87.5(2); C(1)–Ir(1)–Cl(1), 95.0(1); Cl(1)–Ir(1)–N(3),

84.4(1).

6.3.4 General Features of the H2-Hydrogenation of Ketones Catalyzed by Complexes 15, 19,

20 and 21. The ruthenium(II) complex 15 catalyzed the H2-hydrogenation of a variety of

ketones, methyl benzoate and N-(1-phenylethylidene)aniline, and the hydrogenolysis of styrene

oxide with a high substrate to catalyst loadings (catalyst to substrate (C/S) ratio up to 1/11500)

under very mild reaction conditions (8 bar of H2 pressure, 25°C) using either THF or 2-propanol

as the reaction medium, and KOtBu as the base (catalyst to base (C/B) ratio = 1/8). The solvent

2-propanol is an excellent choice for achieving a maximum turnover frequency (TOF) of 17300

h-1 in the H2-hydrogenation of acetophenone, under the same catalysis conditions as above.34 This

system is, by far, the most active ruthenium(II) catalyst containing an N-heterocyclic carbene for

the H2-hydrogenation of ketones.48

The catalytic activity of the iridium(III) complexes 19, 20, and 21 was tested as well for the

hydrogenation of ketones using H2 or 2-propanol as hydrogen source (Tables 6.1, 6.2 and 6.3).

48. (a) Chantler, V. L.; Chatwin, S. L.; Jazzar, R. F. R.; Mahon, M. F.; Saker, O.; Whittlesey, M. K., Dalton Trans. 2008, 2603-2614; (b) Lee, J. P.; Ke, Z. F.; Ramirez, M. A.; Gunnoe, T. B.; Cundari, T. R.; Boyle, P. D.; Petersen, J. L., Organometallics 2009, 28, 1758-1775; (c) Gandolfi, C.; Heckenroth, M.; Neels, A.; Laurenczy, G.; Albrecht, M., Organometallics 2009, 28, 5112-5121.

164The NHC complex 19 catalyzed the H2-hydrogenation of acetophenone in THF in the

presence of KOtBu as the base to 1-phenylethanol in 3 h at 98% conversion under 25 bar H2

pressure at 50°C, with a C/B/S ratio of 1/8/200. These are more forcing conditions than those of

catalyst 15.34 An increase in substrate loading to C/S = 1/600 requires a longer reaction time

(37% conversion in 7 h) and a threefold decrease in turnover frequency (TOF) to 26 h-1 (Table

6.1, entries 1 and 5). The hydrogenation of benzophenone with increased substrate loading led to

similar TOF values (Table 6.2, entries 1 and 2). This is consistent with the formation of an

enolate complex in the case of acetophenone which suppresses catalysis as observed

elsewhere.14b, 32 In addition, the H2-hydrogenation of benzophenone in THF is affected by the

concentrations of the catalyst and hydrogen pressure but is independent of the ketone

concentration (Table 6.2, entries 1-4 and Figure 6.7) as expected since benzophenone cannot

form an enolate.

Figure 6.7. Reaction profiles showing the effect of the concentrations of catalyst, hydrogen and

substrate to the H2-hydrogenation of benzophenone catalyzed by complex 19. (a) [19] = 0.72

mM, [benzophenone] = 0.14 M, P(H2) = 25 bar, red circles; (b) [19] = 0.72 mM, [benzophenone]

= 0.14 M, P(H2) = 15 bar, blue diamonds; (c) [19] = 0.72 mM, [benzophenone] = 0.29 M, P(H2)

= 25 bar, green squares; (d) [19] = 1.2 mM, [benzophenone] = 0.14 M, P(H2) = 25 bar, purple

crosses. All of the reactions were conducted in 25 bar H2 at 50°C in THF and KOtBu was used as

a base (5.9 mM).

165Interestingly, catalysis conducted in 2-propanol under H2 with low substrate and base loadings

(C/B/S = 1/8/200) using 19 was slow, and its activity was nearly identical to that of transfer

hydrogenation (Table 6.1, entry 6 and Table 6.3, Entry 1).

The phosphine complex 20, on the other hand, has low activity in the H2-hydrogenation and

similar activity in the transfer hydrogenation of acetophenone under identical reaction conditions

as those used for 3 (Table 6.1, entry 2 and Table 6.3, Entry 2). The structurally similar

diphenylphosphino-containing complex [RuCp*(P–NH2)py]PF6 (16a) also showed poor activity

in the catalytic H2-hydrogenation of acetophenone compared to 15.34

Table 6.1. The H2-Hydrogenation of Acetophenone Catalyzed by Iridium(III) Complexes.

IrPPh2N

PF6Cl

HH

20

Ir

NN

N

CH3 PF6Cl

22

Ir

NN

N

CH3 PF6HHH

21

Ir

NN

N

CH3 PF6Cl

HH

19

+ + + +

Entrya Complex C/B/Sb ratio Solvent Conversionc (%/hr) TOF (h-1)d

1 19 1/8/200 THF 62/1 98/3 1542 20 1/8/200 THF 6/1 15/4 -f

3 21 1/8/200 THF 9/2 - -4 22 1/8/200 THF 7/2 - -5 19 1/8/600 THF 19/3 37/7 266 19 1/8/200 iPrOH 28/3 99/20 177 19 1/16/200 iPrOH 52/0.3 99/1 4168e 19 1/16/200 iPrOH 20/0.3 98/1 1529 21 1/8/200 iPrOH 41/0.5 99/2 21310 22 1/8/200 iPrOH 3/2 - -f

aReactions were carried out in a 50 mL Parr hydrogenation reactor at 25 bar of H2 pressure at

50°C using THF or iPrOH (6 mL) as the solvent. KOtBu was used as the base. bC/B/S = catalyst

to base to substrate ratio . cConversions were determined by GC and are reported as an average

of two runs. dTOF = turnover frequency, measured from the slope of the linear portion of an

[alcohol] versus time plot. eAn equimolar amount of [2.2.2]cryptand to potassium ions was

added. fTOF not measured.

166Table 6.2. The H2-Hydrogenation of Benzophenone Catalyzed by Iridium(III) Complexes.

Entrya Complex C/B/S ratio

Solvent H2 (bar) Conversionb (%/hr) TOF (h-1)

1 19 1/8/200 THF 25 63/0.5 96/3 3642 19 1/8/400 THF 25 41/0.5 70/3 4723 19 1/8/200 THF 15 41/0.5 83/3 1724c 19 1/5/120 THF 25 61/0.15 95/2 12205 22 1/8/200 THF 25 15/1 25/3 166 22 1/16/200 iPrOH 25 4/2 - -d

aReactions were carried out in a 50 mL Parr hydrogenation reactor at the required H2 pressure at

50°C using THF or iPrOH (6 mL) as the solvent. KOtBu was used as base. bConversions were

determined by GC and are reported as an average of two runs. c[19] = 1.2 mM, the

concentrations of the ketone and base are the same as of entries 1 and 3. dTOF not measured.

Table 6.3. Transfer Hydrogenation of Acetophenone Catalyzed by Iridium(III) Complexes.

Entrya Complex Conversionb (%/hr)

1 19 28/3 69/172 20 27/3 65/203 21 23/3 44/19

aReactions were carried out in iPrOH (6 mL) at 75°C under an argon atmosphere, the C/B/S ratio

was 1/8/200. KOtBu was used as the base. bConversions were determined by GC and are reported

as an average of two runs.

Attempts at catalysis using the hydride-amine complex 21 in the absence of an alkoxide,

whether conducted as direct hydrogenation under H2 in THF or 2-propanol (25 bar H2 pressure,

50°C), or transfer hydrogenation under argon at 75°C in 2-propanol resulted in no conversion of

the starting ketone. Significantly, with an alkoxide base, 21 becomes active in 2-propanol (TOF

= 213 h-1) but less active in THF for the hydrogenation of acetophenone using H2 gas (Table 6.1,

entries 3 and 9). Under argon, 21 is somewhat active for the transfer hydrogenation of

acetophenone in basic 2-propanol solution (Table 6.3, entry 3). Such observations are similar to

those reported for the cationic ruthenium hydride-amine complex 17.32 The neutral complexes

containing a cyclometalated C–NH2 ligand, IrCp*(κ2(C,N)-2-C6H4CR2NH2)H49 and Ru(η6-C6H6)

49. Arita, S.; Koike, T.; Kayaki, Y.; Ikariya, T., Organometallics 2008, 27, 2795-2802.

167(κ2(C,N)-2-C6H4CR2NH2)H,50 are active in the transfer hydrogenation of ketones in the absence

of base at room temperature.

6.3.5 Effect of Alkoxide Base on the H2-Hydrogenation of Acetophenone Catalyzed by

Complex 19. When the ratio of the alkoxide base (KOtBu) to catalyst is increased from 8/1 to

16/1, the chloride complex 19 achieves a similar activity (99% conversion to 1-phenylethanol,

TOF = 416 h-1) to the hydride-amine complex 21 in the presence of 8 equiv. of base (Table 6.1,

entries 7 and 9). The addition of excess metal alkoxides are reported to accelerate the H2- and

transfer hydrogenation of ketones catalyzed by certain ruthenium(II) systems, where the cations

of the added base act as a Lewis acid to stabilize the transition states for the H+/H- transfer from

the catalyst to the ketone.14b, 51 Addition of [2.2.2]cryptand in an equimolar amount to the

potassium ions (C/B/S = 1/16/200) gave full conversion to 1-phenylethanol in 1 h, but with a

smaller TOF value (152 h-1, Table 6.1, entry 8). This suggests that the cations do play a minor

role.14b, 32 In fact, stoichiometric reactions of 19 with different amounts of KOtBu in 2-propanol

gave drastically different products as determined by 1H NMR (vide infra).

Some conclusions can be drawn from the catalytic results obtained by these experiments.

1. Reactions conducted in basic 2-propanol solution starting from the chloride complex 19

lead to the formation of the hydride-amine complex 21 (Scheme 6.2), which has a poor catalytic

activity if the concentration of the alkoxide base present in the beginning of the reaction is small

(for example, a C/B ratio of 1/8). This explains the similar catalytic behaviour when 19 was used

in either the H2- or transfer hydrogenation of acetophenone.

2. A critical ratio of catalyst to base (C/B = 1/8 for the hydride-amine complex 21 and C/B

= 1/16 for the chloride complex 19) is needed for comparable H2-hydrogenation activity. It

appears that 21 is the resting state in catalysis and that the alkoxide base must play a crucial role

in the activation of this hydride.

50. (a) Sortais, J. B.; Ritleng, V.; Voelklin, A.; Holuigue, A.; Smail, H.; Barloy, L.; Sirlin, C.; Verzijl, G. K. M.; Boogers, J. A. F.; de Vries, A. H. M.; de Vries, J. G.; Pfeffer, M., Org. Lett. 2005, 7, 1247-1250; (b) Sortais, J. B.; Barloy, L.; Sirlin, C.; de Vries, A. H. M.; de Vries, J. G.; Pfeffer, M., Pure Appl. Chem. 2006, 78, 457-462; (c) Pannetier, N.; Sortais, J. B.; Dieng, P. S.; Barloy, L.; Sirlin, C.; Pfeffer, M., Organometallics 2008, 27, 5852-5859.51. (a) Hartmann, R.; Chen, P., Angew. Chem. Int. Ed. 2001, 40, 3581-3585; (b) Vastila, P.; Zaitsev, A. B.; Wettergren, J.; Privalov, T.; Adolfsson, H., Chem. Eur. J. 2006, 12, 3218-3225; (c) Wettergren, J.; Buitrago, E.; Ryberg, P.; Adolfsson, H., Chem. Eur. J. 2009, 15, 5709-5718.

1683. Catalysis by 21 conducted in basic 2-propanol was faster than in a basic aprotic solution

using the same concentration of the alkoxide base. This is reversed when 19 was used. The

alcohol solvent must participate in catalysis which acts as a reactant and/or as a proton shuttle.

6.3.6 The Importance of the NH2 Group in the Iridium(III) System on its Activity in the

Catalytic Hydrogenation of Ketones. Complex 22 which does not contain an N–H

functionality catalyzed the hydrogenation of acetophenone and benzophenone in THF and

KOtBu very slowly to 1-phenylethanol in 2 h to 7% conversion, and to diphenylmethanol in 3h

to 25% conversion. respectively, under 25 bar H2 and 50°C (C/B/S = 1/8/200, Table 6.1, entry 4

and Table 6.3, entry 5). Catalysis was even slower when 2-propanol was used as the solvent (C/B

= 1/16, Table 6.1, entry 10 and Table 6.3, entry 6). This is slow compared to 19 (96% conversion

in 3 h), which contains an N–H group, under identical catalysis conditions. This is in contrast to

the previously reported systems, [Ru(η6-p-cymene)(C–NH2)Cl]PF6 (13) and the N,N-dimethyl

analogue ([Ru(η6-p-cymene)(C–NMe2)Cl]PF6·1.5 DMSO (18), see Chapter 5), both of which

showed similar activities in catalyzing the hydrogenation of acetophenone.32 The N–H group of

our iridium system, therefore, must be important in catalysis, consistent with an outer sphere

bifunctional mechanism for ketone hydrogenation (Step B in Scheme 6.1).

6.3.7 Selectivity in the Hydrogenation of an α,β-unsaturated ketone Catalyzed by

Complexes 15 and 19. Under similar reaction conditions to the hydrogenation of acetophenone

(Scheme 6.5), the ruthenium(II) complex 15 catalyzed the selective reduction of the polar bond

to give trans-4-phenyl-but-3-en-2-ol (89% conversion) and 4-phenylbutan-2-ol (4% conversion)

and none of the saturated ketone, 4-phenylbutan-2-one within 1 h. The iridium(III) complex 19

also catalyzed the selective reduction of the ketone in the same substrate giving trans-4-phenyl-

but-3-en-2-ol (88% conversion) and 4-phenylbutan-2-ol (8% conversion), and the saturated

ketone, 4-phenylbutan-2-one (3% conversion) in 5 h, under 25 bar of H2 pressure at 50°C in 2-

propanol, and in the presence of an excess of alkoxide base (16 equiv. with respect to catalyst,

Scheme 6.5). The selectivity that complexes 15 and 19 exhibit is characteristic of an outer sphere

bifunctional mechanism. It is known that the reduction of the olefin can also proceed via a 1,4-

addition reaction utilizing the same mechanism.52

169Scheme 6.5. The Hydrogenation of trans-4-Phenyl-but-3-ene-2-one Catalyzed by Complexes 15

and 19.a

aReactions were carried out in a 50 mL Parr hydrogenation reactor at the required H2 pressure

and temperature in THF or iPrOH (6 mL) and KOtBu was used as base. Conversions were

determined by GC and are reported as an average of two runs.

6.3.8 Effect of Alcohol and Other Additives on the H2-Hydrogenation of Acetophenone

Catalyzed by the Ruthenium(II) Complex 15. Reactions carried out in THF gave sigmoidal-

type reaction profiles with variable induction periods (10 – 60 min). On the other hand, a

reaction that was conducted in 2-propanol did not show any sigmoidal behavior in the reaction

profile (Figure 6.8).

The effect of different additives on this induction period was then investigated. The addition

of the product alcohol, 1-phenylethanol, at the beginning of the reaction (up to 0.4 M in THF)

decreased the induction period. In addition, the induction period increased by roughly six fold if

the pressure of H2 is decreased from 8 to 2 bar. There was little effect on changing the

concentrations of acetophenone or the catalyst by two fold (Figure 6.9). The addition of pyridine

to the reaction mixture retarded catalysis (Figure 6.8). As well, the possibility of the formation of

ruthenium nanoparticles was examined and this was deemed unlikely by conducting the mercury

test in the hydrogenation of 4'-chloroacetophenone in basic THF.34

It appears that there exists a competition between H2 and pyridine to coordinate to the

catalytically active species. The presence of alcohol selectively favors the binding and

heterolytic splitting of η2-H2 by acting as a proton shuttle.6c, 12e, 19b, 20b, 22a This system will have a

different rate law reported for the amido complex RuH((S)-BINAP)(app) (app = 2-amido-2-(2-

pyridyl)-propane) which displayed autocatalysis in the presence of alcohols.19b

52. (a) Ito, M.; Kitahara, S.; Ikariya, T., J. Am. Chem. Soc. 2005, 127, 6172-6173; (b) Ikariya, T.; Gridnev, I. D., Chem. Rec. 2009, 9, 106-123.

[15] or [19] cat.

[15]: 8 bar H2, 25°C, THF

O

OH

O

OH

89% in 1 h

0%

4%

KOtBu

[15] [19]

88 % in 5 h

3%

8 %

C/B/S = 1/8/600 C/B/S = 1/16/200

[19]: 25 bar H2, 50°C, iPrOH

170

Figure 6.8. Reaction profiles showing the effect of alcohols and pyridine on the hydrogenation

of acetophenone catalyzed by complex 15 in (a) basic THF, red circles; (b) basic 2-propanol,

blue diamonds; (c) basic THF, [1-phenylethanol] = 0.2 M, green squares; (d) basic THF, [1-

phenylethanol] = 0.4 M, orange triangles; (e) basic THF, [pyridine] = 0.030 M, purple crosses.

All of the reactions were conducted with 8 bar H2 at 25°C and KOtBu was used as the base. The

C/B/S ratio was 1/8/2515.

Figure 6.9. Reaction profiles showing the effect of the concentrations of catalyst, hydrogen and

substrate on the hydrogenation of acetophenone catalyzed by complex 15, (a) [15] = 0.77 mM,

[acetophenone] = 1.9 M, P(H2) = 8 bar, red circles; (b) [15] = 1.3 mM, [acetophenone] = 1.9 M,

P(H2) = 8 bar, blue squares; (c) [15] = 0.77 mM, [acetophenone] = 0.97 M, P(H2) = 8 bar, green

triangles; (d) [15] = 0.77 mM, [acetophenone] = 1.9 M, P(H2) = 2 bar, orange crosses. All of the

reactions were conducted with 25oC in THF and KOtBu was used as the base (5.9 mM).

1716.3.9 Deuterium Labelling Studies Using the Ruthenium(II) Complex 15. In order to find

evidence for an alcohol-assisted mechanism in the hydrogenation of ketone by complex 15,

acetophenone was deuterated using D2 gas in 2-propanol (OH) and 2-propanol-d1 (OD, Table

6.4). Full conversion to the deuterated product was achieved in 30 min. Analysis of the 1H NMR

spectra of the products revealed significant deuteration at the α-carbon and the hydroxyl group of

1-phenylethanol when both D2 and 2-propanol-d1 were used, but less when D2 and 2-propanol

were used (Table 6.4). These results suggest significant H/D scrambling took place at the active

ruthenium species with participation of the alcohol solvent. Further analysis of the 2H NMR

spectra showed deuteration of the hydroxyl group of 2-propanol but not at its α-carbon.

Table 6.4. Deuteration of Acetophenone and 2-Propanol Catalyzed by Complex 15.

Deuteriuma Source Deuterium Content in 1-Phenylethanol (%)b In 2-Propanol (%)b

α-CD OD group CDnH3-n group (n = 1-3)

OD group

D2/iPrOH 42 11 - 27D2/iPrOD 80 76 71 84

aReactions were carried out in a 50 mL Parr hydrogenation reactor at 8 bar of D2 pressure at 25°C

using the appropriate solvent (6 mL). KOtBu was used as the base. The catalyst/base/

substrate/solvent ratio was 1/8/898/17060. Complete conversion to the product alcohol was

achieved in 30 min. bThe deuterium content of the 1-phenylethanol and 2-propanol were

determined by 1H and 2H NMR.

On the other hand, the hydroxyl deuterium of 2-propano1-d1 was not retained after catalysis

(lowered from 100% to 84% deuteration, Table 6.4) further supporting the idea that H/D

scrambling has taken placed. This is evidence that 2-propanol is acting as a proton shuttle.20b Of

note, deuteration of the methyl group of 1-phenylethanol was observed when D2 and 2-propanol-

d1 were used in catalysis. This is expected due to the base-catalyzed deuteration of enolizable

ketones as reported elsewhere.14b, 32 These experiments support the alcohol-assisted heterolytic

splitting of η2-H2 on the active ruthenium species starting from complex 15 when activated (Step

A in Scheme 6.1).

6.3.10 Effect of Alcohol on the H2-Hydrogenation of Acetophenone Catalyzed by

Iridium(III) Complexes 19 and 21. The effect of alcohols on the hydrogenation of

acetophenone catalyzed by the chloride complex 19 and hydride-amine complex 21 was further

172investigated (Figures 6.10 and 6.11). A sigmoidal-type reaction profile was again observed with

variable induction periods when either acetophenone or benzophenone was hydrogenated using

either 19 in THF or 21 in 2-propanol as the catalyst with KOtBu as the base. The addition of 1-

phenylethanol at the beginning of the reaction (up to 0.030 M in THF, 40 mol%) decreases the

induction period when 19 is present but increases the induction period when 21 is present

(Figures 6.10 and 6.11). The product alcohol reacts with base to form 1-phenylethoxide. This

readily reacts with 19 forming the hydride-amine complex 21 and acetophenone. (vide infra).

This has the effect of decreasing the concentration of enolate of acetophenone in the reaction

mixture, and makes it less available to coordinate to the active iridium species. The presence of

enolate molecules is believed to slow down catalysis by competing with the coordination of H2

as observed elsewhere.14b, 32 Deuterium labelling studies support the formation of enolate (see

below). On the other hand, the presence of 1-phenylethanol at the beginning of catalysis using

the hydride-amine complex 21 and KOtBu changes the basicity of the reaction mixture. This

might be important to slow down the formation of the active iridium species during catalysis.


acetophenone catalyzed by the chloride complex 19 in the presence of KOtBu, in (a) basic THF,

red circles, C/B = 1/8; (b) basic 2-propanol, blue diamonds, C/B = 1/8; (c) basic THF, [1-

phenylethanol] = 0.015 M, C/B = 1/8, green squares; (d) basic 2-propanol, C/B = 1/16, purple

triangles. All of the reactions were conducted using 25 bar H2 at 50°C. The C/S ratio was 1/200.

173


acetophenone catalyzed by the hydride-amine complex 21 in (a) basic 2-propanol, blue

diamonds; (b) basic THF, red squares; (c) basic 2-propanol, [1-phenylethanol] = 0.030 M, green

triangles. All of the reactions were conducted using 25 bar H2 at 50°C and KOtBu was used as the

base. The C/B/S ratio was 1/8/200.

The fact that the solvent alcohol and an excess of alkoxide base is required for catalysis

involving either catalyst 19 or 21 in order to achieve high and comparable activity, suggests that

they have a role to play in catalysis. The alcohol may play a similar role as in the ruthenium(II)

system to accelerate catalysis by acting as a proton shuttle in the heterolytic splitting of η2-H2 in

step A of Scheme 6.1.

6.3.11 Deuterium Labelling Studies Using the Iridium(III) Complex 19. To gain further

insight into the effect of 2-propanol and 1-phenylethanol on the hydrogenation of acetophenone

catalyzed by complex 19, acetophenone was first deuterated using D2 gas in THF in the presence

of 20 mol% 1-phenylethanol and KOtBu (Table 6.5, entry 1). Full conversion to the product

alcohol was achieved in 18 h. Analysis of the 1H NMR and 2H NMR spectra of the deuterated

product suggested 80% deuteration at the α-carbon, 14% at the hydroxyl group, and 36% at the

methyl group of 1-phenylethanol. No deuteration was observed at the phenyl ring. Base-

catalyzed deuteration of the enolizable acetophenone is responsible for such a deuterium

distribution on 1-phenylethanol.14b, 32 In contrast, when 1-phenylethanol was deuterated for 6 h

under similar reaction conditions as above, deuteration was also observed at the α-carbon,

hydroxyl and the methyl group, but to a minor extent (Table 6.5, entry 2). This supports the

174formation of acetophenone and the hydride-amine complex 21 via the formation of an alkoxide

intermediate, [IrCp*(C–NH2)(O-CHPhCH3)]+, in which the β-hydrogen of 1-phenylethoxide

ligand can eliminate.2a, 5c, 14a, 18, 39-40, 53 Acetophenone that formed was then deuterated in the

presence of an active iridium species.

Table 6.5. Deuteration of Acetophenone and 1-phenylethanol Catalyzed by Complex 19.

Entry Reaction Conditionsa Substrate Deuterium Content in 1-Phenylethanol (%)b

α-CD OD group CDnH3-n group (n = 1-3)

1 10 bar D2, THF, 18 hc Acetophenone,1-phenylethanol

80 14 36

2 10 bar D2, THF, 6 hc 1-Phenylethanold 9 42 153 8 bar D2, iPrOH, 6 he Acetophenone 30 -f 14 10 bar D2, iPrOH, 6 he 1-Phenylethanol - Negligiblef -

aReactions were carried out in a 50 mL Parr hydrogenation reactor at the required D2 pressure at

50°C using the appropriate solvent (6 mL). KOtBu was used as the base. bThe deuterium content

of the 1-phenylethanol and 2-propanol were determined by 1H and 2H NMR, no deuteration was

observed on the phenyl ring of the product alcohol. cThe C/B/S ratio was 1/8/200. d20 mol% of

1-phenylethanol was used with respect to [19]. eThe C/B/S ratio was 1/16/200. fDeuteration at the

OD group of 2-propanol was observed.

When acetophenone was deuterated using D2 gas in 2-propanol in the presence complex 19

and excess base (Table 6.5, entry 3), deuteration at the α-carbon was significantly smaller (30%

deuteration) and deuteration at the hydroxyl and the methyl group was negligible. However, 2H

NMR of the reaction mixture showed that the extent of deuteration of the hydroxyl group of 2-

propanol was much greater than that at the α-carbon of 1-phenylethanol. In fact, the effect of 2-

propanol by acting as a proton shuttle in the heterolytic splitting of D2 is more important than the

product alcohol, as evident by a reaction of 1-phenylethanol with 0.5 mol% of complex 19 in

basic 2-propanol (Table 6.5, entry 4). In this case, the hydroxyl group of 2-propanol was

deuterated but not that of 1-phenylethanol.

6.3.12 Stoichiometric Reactions Using Complex 19. In order to identify possible intermediates

in the catalytic cycle involving 19, KOtBu, acetophenone and H2, stoichiometric reactions were

53. Laxmi, Y. R. S.; Backvall, J. E., Chem. Commun. 2000, 611-612.

175monitored by 1H NMR spectroscopy. The reaction of 19 and 2 equiv. of KOtBu under 1 bar of H2

at 50°C in THF only led to 5% conversion to the hydride-amine complex 21. A reaction

conducted at higher H2 pressure (25 bar) and with more base (5 or 12 equiv.) in THF followed by

evaporation of the solvent and dissolution in acetonitrile-d3 afforded at least three species as

identified by three resonances at about 3.6 ppm in the 1H NMR spectrum for the CH3 group on

the C–NH2 ligand. These were the monohydride complex 21, a cis-dihydride complex containing

two peaks at -17.92 and -18.34 ppm with JHH = 9.83 Hz,54 and another species that does not

contain any hydride peaks. The ratio between the aforementioned hydride containing complexes

varies with the initial concentrations of 19 and base.

When 19 was reacted with KOtBu in 25 bar of H2 at 50°C in 2-propanol, the products that

were formed depended on the amount of base that was added. The addition of 8 equiv. of KOtBu

at the beginning of the reaction gave, upon evaporation of the solvent and dissolution in

acetonitrile-d3, at least three species that were observed by three resonances at around 3.6 ppm in

the 1H NMR spectrum for the CH3 group on the C–NH2 ligand associated with 21 (63%) and two

other species that did not contain any hydride peaks (37%, CH3 peak resonates at 3.69 and 3.72

ppm). When more base was added (16 equiv.), the species that has the CH3 peak at 3.69 was

observed in 67% abundance. There were two other species that were observed in equal amounts

as well, one of which gave a hydride peak at -19.72 ppm. The signals pertaining to the hydride-

amine complex 21 were lost. Although the species in this complicated mixture were not

identified further, this shows that complex 21 reacts further with excess alkoxide base.

Further, a reaction of complex 19 with potassium 1-phenylethoxide in warm THF (50°C)

under argon afforded 21 and acetophenone in 21% conversion as a result of β-hydrogen

elimination of 1-phenylethoxide. This also left behind the starting complex as identified by 1H

NMR in acetonitrile-d3. Heating such sample overnight in a sealed NMR tube afforded

conversion to 21 in 63% and acetophenone in 70%. All these results establish the formation of

complex 21 at the initial stage of catalysis, especially when the concentration of the active

catalyst is low and there exists a similar amount of alkoxide anions containing β-hydrogen in the

reaction mixture. The activation of such a complex by an alkoxide base, therefore, becomes

important at a later stage of catalysis.

54. (a) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J. W.; Crabtree, R. H., J. Am. Chem. Soc. 2002, 124, 10473-10481; (b) Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grützmacher, H., Chem. Eur. J. 2006, 12, 5849-5858; (c) Dzik, W. I.; Smits, J. M. M.; Reek, J. N. H.; de Bruin, B., Organometallics 2009, 28, 1631-1643.

1766.3.13 The Conventional Non-Alcohol Assisted Outer Sphere Bifunctional Mechanism. The

catalytic cycles that involve the outer sphere bifunctional mechanism in the absence of alcohol

for the ruthenium(II) (complex 15) and iridium(III) (complexes 19 and 21) systems were

investigated by Density Functional Theory (DFT). The MPW1PW91 functional was used as this

gives better prediction of energy barriers and transition states for 4d and 5d metals.55

Simplifications were made to ease computation by replacing the Cp* ligand with Cp; acetone and

2-propanol were used to model the ketone and the product alcohol.

In the conventional outer sphere mechanism that involves the action of M–H and N–H groups

(Scheme 6.6), the addition of base to the precatalyst afforded the amido complex A, which

results from the deprotonation of the N–H group. Such a complex is responsible for activating

dihydrogen to yield a metal hydride complex D via an H2 addition step to the metal center

(TSB,C) and subsequent heterolytic splitting at the metal center (TSC,D). The activation of H2 at

the amido complex is rate-determining and this should have the largest energy barrier of the

overall catalytic cycle. The fast, low barrier step, then follows for the transfer of H+/H- from D to

the ketone in the outer sphere fashion to afford the product alcohol and A. 6c, 12e, 12k, 12m, 13a, 14a, 14b, 19b

According to calculations (Figure 6.12), the free energy barriers for the activation of H2 (the

coordination and heterolytic splitting of H2) by the neutral ruthenium(II) and cationic iridium(III)

species are 14.1 and 22.6 kcal/mol, respectively. The heterolytic splitting of H2 leads to a more

reactive ruthenium(II) hydride DRu (-8.8 kcal/mol relative to ARu and H2) but a more

thermodynamically stable iridium(III) hydride DIr (-23.5 kcal/mol relative to AIr and H2). The

free energy barriers for the transfer of H+/H- from DRu to acetone and to acetophenone are 16.9

and 12.3 kcal/mol, respectively. By contrast it is unfavourable to transfer H+/H- from DIr to

acetone (35.9 kcal/mol). In addition to a stronger Ir–H bond that is formed due to relativistic

effect on going from a 4d (Ru) to a 5d (Ir) metal, the cationic charge of the iridium may

deactivate the metal hydride as was observed for the cationic ruthenium hydride-amine complex

17.32

55. Lynch, B. J.; Truhlar, D. G., J. Phys. Chem. A 2001, 105, 2936-2941.

177Scheme 6.6. Computed Outer Sphere Bifunctional Mechanism in the Hydrogenation of Acetone

Catalyzed by Complexes of Ruthenium(II) and Iridium(III).

The computed results suggest well-balanced energy barriers for the ruthenium(II) system. The

hydride complex (DRu) which is formed upon the activation of H2 by ARu is readily consumed

when it transfers its H+/H- to the ketone in the outer sphere. On the other hand, the calculated

results show that the iridium(III) hydride complex (DIr) is the resting state of the catalytic cycle,

and the transfer of H+/H- to the ketone in the outer sphere is very difficult. This is in line with the

observation that the hydride-amine complex 21 does not react with acetophenone in either

stoichiometric or catalytic reactions in the absence of base.

Of interest, the geometric parameters for the optimized transition state structures for the

heterolytic splitting of H2 (TSC,D, Figure 6.13) and the transfer of H+/H- to acetone (TSE,F, Figure

6.14) of both systems are surprisingly similar, except for a longer O–H interaction (O–H…N

distance: 1.61 Å for ruthenium and 1.38 Å for iridium) for the ruthenium(II) system. An Intrinsic

Reaction coordinate (IRC) calculation that was performed on TS(Ru)E,F located a local minima,

M NNN

CH3

H

MH NNN

CH3

HH

H2

OOH

H

n+ n+

M NNN

CH3

H

n+

HH

MH NNN

CH3

HH

n+

OM = Ru, n = 0M = Ir, n = 1

MH NNN

CH3

HH

n+

M NNN

CH3

H

n+

HH M N

NN

CH3

H

n+

H

H

H M NNN

CH3

H

n+

H

O

M NNN

CH3

H

n+

O

H

H

A

B

TSB,C C

TSC,D

D

EF

TSE,F

Outer SphereBifunctional Mechanism

178which revealed a 2-propoxide anion that is hydrogen-bonded via oxygen to the N–H group on

the C–NH2 ligand, along with an agostic C–H interaction of the 2-propoxide anion with the

ruthenium(II) center. Subsequent geometry optimization and normal mode analysis provided that

this structure (FRu') is 0.9 kcal/mol more stable than TS(Ru)E,F (∆G = 7.2 kcal/mol relative to

ARu, H2 and acetone). This has a O–H distance of 1.39 Å, a C–H distance of 1.26 Å, and a Ru…H

distance of 1.85 Å. These geometric parameters are similar to an analogous structure reported by

Gusev and co-workers.11h A QST3 or a QST2 calculation that were performed for the protonation

of the 2-propoxide anion by the N–H group on the C–NH2 ligand giving FRu failed to locate a

transition state structure. All these suggest that the transfer of a H+/H- couple from the hydride-

amine complex to the ketone in the outer-sphere for the ruthenium(II) system might occur in a

stepwise fashion.11h, 17

Figure 6.12. The free energy profile for the outer sphere bifunctional mechanism in the H2-

hydrogenation of acetone starting from A and moving to the right. Pathway colored in blue

represents the ruthenium(II) system and the one in red represents the iridium(III) system. The gas

phase free energies (1 atm, 298 K) are reported relative to A, hydrogen and acetone in kcal/mol.

179

Figure 6.13. Computed transition state structures for the heterolytic splitting of H2 (TSC,D) of the

ruthenium(II) (left) and the iridium(III) system (right). The bond lengths (Å) are given in the

structures. The color code for the atoms are: ruthenium (orange), iridium (yellow),

nitrogen(blue), carbon (grey) and hydrogen (white).

Figure 6.14. Computed transition state structures for the transfer of a proton/hydride pair to

acetone (TSE,F) from the ruthenium(II) (above) and iridium(III) hydrides (below). The bond

lengths (Å) are given in the structures. The color code for the atoms are: ruthenium (orange),

iridium (yellow), nitrogen (blue), oxygen (blue), carbon (grey) and hydrogen (white).

1806.3.14 The Alcohol-Assisted Outer Sphere Bifunctional Mechanism for the Ruthenium(II)

System. In the presence of 2-propanol (Scheme 6.7), or when the concentration of the product

alcohol builds up, the free energy barriers for the coordination and the heterolytic splitting of H2

become lower (ΔGǂ = 11.1 and 8.5 kcal/mol respectively) starting from Aalc (Figure 6.15, Aalc

corresponds to F in Scheme 6.6).

The transition state structure of the alcohol-assisted heterolytic splitting of H2 shows that the

protons neighbouring to the alcoholic oxygen are held in close proximity by the formation of two

hydrogen-bonds via O...H interactions (H2–O: 1.74; H3–O: 1.36 Å, Figure 6.16). These results

are supportive of an alcohol-assisted mechanism where the alcoholic proton is shuttled between

the coordinated dihydrogen and the amido nitrogen via a six-membered ring transition state 6c, 12e,

12m, 13a, 14b, 19b, 20b, 22 Andersson and co-workers have specifically calculated a similar transition state

structure for the alcohol-assisted heterolytic splitting of H2 of a structurally similar

RuCp*(diamine)X system, and the effect of methanol on the free energy barriers of H2

coordination and its activation are pronounced given the level of theories of calculations.12e

Scheme 6.7. Computed Reaction Pathways of the Activation of H2 by Complex A in the

Presence of 2-Propanol.

In addition, the free energy barrier for the transfer of a proton/hydride couple to acetone is

16.2 kcal/mol if a six-membered ring transition state is assumed.19b The alcohol, therefore, has a

Ru NNN

CH3

H

RuH NNN

CH3

HH

H2

O

OH

H

Ru NNN

CH3

H

HH

Ru NNN

CH3

H

HH

H Ru NNN

CH3

H

H

Aalc

Balc TSB,C

Calc

TSC,DDalc

Alcohol-Assisted Outer SphereBifunctional Mechanism

O

H

H

O

H

H

O

H

H

Ru NNN

CH3

H

HH

O

H

H

OH HO

HH

alc

alc

Ealc → TSE,F → Falcalc

181minor effect on such a transition state as the energy barriers with and without alcohol were

similar (ΔGǂ = 16.9 kcal/mol).19b On the other hand, the induction period that was observed when

an aprotic solvent was used during catalysis can be explained by a competition between pyridine

and dihydrogen to coordinate to the amido complex RuCp*(C–NH). The energy barriers for the

coordination of pyridine and hydrogen to A are very similar (ΔGǂ = 15.7 and 14.1 kcal/mol),35

and the presence of alcohol provides a lower energy pathway to effectively convert Aalc and H2 to

the hydride complex Dalc, which will be readily consumed by transferring its H+/H- to acetone in

the outer sphere. This has the effect of driving the equilibrium between A plus pyridine and its

adduct, RuCp*(C–NH)(py), to the left.

Figure 6.15. The free energy profile for the outer sphere bifunctional mechanism in the

activation of H2 starting from A and moving to the right (blue pathway), and in the presence of 2-

propanol staring from Aalc and moving to the right (red pathway). The gas phase free energies (1

atm, 298 K) are reported relative to A, hydrogen and acetone in kcal/mol.

182

Figure 6.16. Computed transition state structure for the heterolytic splitting of H2 (TSC,Dalc) by

the ruthenium(II) system in the presence of 2-propanol. The bond lengths (Å) are given in the

structure. The color code for the atoms are: ruthenium (orange), nitrogen (blue), oxygen (red),

carbon (grey) and hydrogen (white).

6.3.15 The Alcohol-Assisted Outer Sphere Bifunctional Mechanism Involving Iridium(I)

Intermediates. As the cationic hydride-amine complex 21 must be activated during catalysis by

an alkoxide base, H2 and 2-propanol, we proposed, on the basis of computational results, the

formation of a neutral amido-hydride complex R that results from the deprotonation of the N-H

group of 21 (modeled as DIr of Scheme 6.6 in calculations) by 2-propoxide. This has a 2-

propanol molecule hydrogen-bonded to the amido nitrogen (Scheme 6.8). An alternative

structure Q can also form by the reaction of the cationic hydride complex DIr and 2-propoxide.

This has a coordinated η5-Cp, hydride and 2-propoxide and a decoordinated amine group of the

C–NH2 ligand. This structure is thermodynamically less stable than R (ΔG = 11.4 kcal/mol,

Scheme 6.8). As a coordination site is required for the activation of H2 starting from structures Q

or R, we have evaluated three feasible pathways, which included reductive elimination of 2-

propanol from Q, ring slippage of the Cp* ligand of R, and hydride migration to the Cp* ligand of

R. Bergman and co-workers proposed a similar pathways in the reductive elimination of ethanol

from IrCp*(PPh3)(H)(OEt), and subsequent coordination of a neutral ligand L forming the

iridium(I) species IrCp*(PPh3)L.42b To our surprise, the alcohol-assisted outer-sphere bifunctional

mechanism involving a hydride migration to the Cp* ligand was an energetically favourable

pathway for ketone hydrogenation: this will be presented in detail. The migration of a

coordinated ligand (hydrides,56 alkyl or aryl groups57) to the η5-Cp* ligand56b, 56c, in particular in

an endo fashion,56a, 56b, 57b, 58 is not common, but there are examples of stable iron(II) and

183ruthenium(II) complexes containing such a η4-Cp ligand as a result of an exo59 addition of the

hydride ligand to the η5-Cp ring. The two other pathways, reductive elimination of alcohol and

the ring slippage of the η5-Cp* ring, are characterized by higher free energy barriers to transfer a

hydride to acetone in the outer sphere (71.5 kcal/mol for the reductive elimination mechanism

and 34.1 kcal/mol for the ring slippage mechanism).35 The reductive elimination pathway,

however, is not feasible as this involves the decoordination of the amine throughout the catalytic

cycle, while experimental evidence supports the role of the N-H group.

Scheme 6.8. Computed Hydride Migration Pathway from the Ir–H bond to the Coordinated Cp

Ligand Starting from R.

According to the mechanism shown in Scheme 6.8, the amido-hydride complex S was formed

by the loss of a 2-propanol molecule from R. The hydride ligand from S can then add to the Cp

ligand, which is an uphill process and slightly entropically disfavoured (ΔGǂ = 35.1 kcal/mol

from S, ΔSǂ = -3.0 cal/mol·K, Scheme 6.8). Interestingly, replacing the Cp with a Cp* ligand

gave a very similar barrier to this process (ΔGǂ = 35.2 kcal/mol from S*, ΔSǂ = -1.2 cal/mol·K).

This contributes to the induction period that was observed in the H2-hydrogenation of

acetophenone in 2-propanol catalyzed by 21 in the presence of KOtBu. The analogous hydride

migration product of ruthenium(0), Ru(η4-CpH)(C–NH2) is thermodynamically less stable than D

(ΔG = 23.8 kcal/mol), although the barrier for hydride migration is similar in energy (ΔGǂ = 35.3

kcal/mol from D).

56. (a) Hirsekorn, F. J.; Rakowski, M. C.; Muetterties, E. L., J. Am. Chem. Soc. 1975, 97, 237-238; (b) McAlister, D. R.; Erwin, D. K.; Bercaw, J. E., J. Am. Chem. Soc. 1978, 100, 5966-5968; (c) Gusev, O. V.; Morozova, L. N.; Peganova, T. y. A.; Petrovskii, P. V.; Ustynyuk, N. A.; Maitlis, P. M., J. Organomet. Chem. 1994, 472, 359-363; (d) Lin, S. B.; Day, M. W.; Agapie, T., J. Am. Chem. Soc. 2011, 133, 3828-3831.57. (a) Meanwell, N. J.; Smith, A. J.; Maitlis, P. M., Dalton Trans. 1986, 1419-1424; (b) Wu, F.; Dash, A. K.; Jordan, R. F., J. Am. Chem. Soc. 2004, 126, 15360-15361.58. Cadenbach, T.; Gemel, C.; Schmid, R.; Fischer, R. A., J. Am. Chem. Soc. 2005, 127, 17068-17078.59. (a) Devies, S. G.; Hibberd, J.; Simpson, S. J.; Thomas, S. E.; Watts, O., Dalton Trans. 1984, 701-709; (b) DiBiase Cavanaugh, M.; Gregg, B. T.; Chiulli, R. J.; Cutler, A. R., J. Organomet. Chem. 1997, 547, 173-182; (c) Brown, D. A.; Deignan, J. P.; Fitzpatrick, N. J.; Fitzpatrick, G. M.; Glass, W. K., Organometallics 2001, 20, 1636-1645.

S (-0.2)

Ir NNN

CH3

HO

H

HH

R (0.0)

Ir NNN

CH3

H

H

TSS,HI (34.9)

Ir NNN

CH3

H

H

1

OHH

HI1 (3.3)

Ir NNN

CH3

H

HH

*Free energy (kcal/mol) given in parentheses.

CH3N

N

Ir

NHH

OH

H

Q (11.4)

184Scheme 6.9. Computed Alcohol-assisted Outer Sphere Bifunctional Mechanism in the H2-

Hydrogenation of Acetone Catalyzed by Complexes of Iridium(I).

Significantly, this neutral iridium(I) system, containing a η4-cyclopentadiene ligand, allows

efficient bifunctional catalysis via the outer sphere mechanism (Scheme 6.9). The square planar

amido complex HI1, can heterolytically split a coordinated H2 molecule (ΔGǂ = 28.1 kcal/mol) in

the transition state TS(HI)3,4 (Figure 6.17). The distorted square pyramidal hydride-amine

complex HI4, which has an apical hydride ligand (Ir–H distance = 1.64 Å), then completes the

cycle via the transition state TS(HI)5,6 by transferring a proton/hydride couple to acetone in the

outer sphere forming the amido complex HI1 and 2-propanol with a free energy barrier of 16.5

kcal/mol (Figure 6.18). It appears the neutral charge of the iridium(I) system is an important

factor in determining the reactivity of the bifunctional M–H/N–H pair during catalysis.

The presence of 2-propanol in the system (Scheme 6.9, Figure 6.18) effectively lowers the

free energy barrier for the heterolytic splitting of H2 by acting as a proton shuttle (ΔGǂ = 20.7

HH

HI2 TS(HI)3,4

TS(HI)5,6

O

H

H

H2

O

O

HI5

HI4

HI3Ir N

NN

CH3

H

Ir NNN

CH3

H

HH

Ir NNN

CH3

H

HH

Ir NNN

CH3

H

H

Ir NNN

CH3

H

HH

O Ir NNN

CH3

H

H

H

H

H

H

H

H

HH

H

H

H

H

H

Ir NNN

CH3

HO

H

H

HI6

HH

Ir NNN

CH3

HO

H

H

HI1

HH

O

H

H

O

H

H

HOH H

OH H

O

H

H

O

H

H

OH H

Alcohol-Assisted Outer SphereBif unctional Mechanism Involving

Iridium( I) intermediatesalc

alc

alc

alc

alc

alc

alc

alc

TS(HI)2,3

Ir NNN

CH3

H

HH

HH

O

H

H

alc

185kcal/mol). The transition state structure TS(HI)3,4alc shows that the protons neighbouring the

hydroxyl oxygen are even in closer proximity by the formation of two hydrogen-bonds via O...H

interactions (H2–O: 1.67; H3–O: 1.24 Å, Figure 6.17). On the other hand, the free energy

barriers for the coordination of H2 to HI1alc and the transfer of proton/hydride couple to acetone

in the outer sphere are less affected by the presence of a hydrogen-bonded 2-propanol molecule

in the system (ΔGǂ = 20.5 and 17.0 kcal/mol, respectively). All these provide evidence to support

an alcohol-assisted outer sphere bifunctional mechanism (Scheme 6.1), and serve to explain the

importance of 2-propanol as a solvent during catalysis.

Figure 6.17. Computed transition state structures for the non-alcohol assisted (TS(HI)3,4, left)

and the alcohol-assisted heterolytic splitting of H2 (TS(HI)3,4alc, right) by the iridium(I) system.

The bond lengths (Å) are given in the structures. The color code for the atoms are: iridium

(yellow), nitrogen (blue), oxygen (red), carbon (grey) and hydrogen (white).

6.3.16 Disfavored Inner Sphere Mechanisms Involving Cationic Iridium(III) Intermediates.

As an alternative to the outer sphere bifunctional mechanism, we investigated the possibility that

a cationic iridium(III) alkoxide complex G, [Ir(η5-Cp)(C–NH2)(OiPr)]+, is first formed instead of

the amido complex A upon activation of the precatalyst (Complex 19) by 2-propoxide. The

energy difference between A and G is 1.7 kcal/mol.12d In order to provide a vacant coordination

site for the activation of H2, ring slippage of the Cp ligand from η5 to η3 or the decoordination of

the amine group might occur.12d, 20a, 32 The energy barriers that were computed for the activation

of H2 are 55.0 kcal/mol and 35.6 kcal/mol, respectively (Scheme 6.10). Bäckvall and co-workers

have calculated a higher energy barrier for a η5 to η3 ring slip compared to the dissociation of CO

186from their racemization catalyst, Ru(η5-C5Ph5)(CO)2Cl, before the association of a ketone

molecule.60 They then proposed a dissociative mechanism based on experimental findings41 and

this is further validated by Nolan and coworkers.39 In fact, such an energy barrier difference is in

line with our previous experimentation.32

Figure 6.18. The free energy profile for the (a) alcohol-assisted outer sphere bifunctional

mechanism (blue pathway) and (b) the non alcohol-assisted outer sphere bifunctional mechanism

(red pathway) in the H2-hydrogenation of acetone starting from the amido complex HI1 and

moving to the right. The gas phase free energies are reported relative to HI1, hydrogen, acetone

and 2-propanol for the blue pathway, and to HI1, hydrogen and acetone for the red pathway, in

kcal/mol.

60. Nyhlen, J.; Privalov, T.; Backvall, J. E., Chem. Eur. J. 2009, 15, 5220-5229.61. (a) Atwood, J. D.; Brown, T. L., J. Am. Chem. Soc. 1976, 98, 3160-3166; (b) Bryndza, H. E.; Domaille, P. J.; Paciello, R. A.; Bercaw, J. E., Organometallics 1989, 8, 379-385; (c) Caulton, K. G., New J. Chem. 1994, 18, 25-41; (d) Flood, T. C.; Lim, J. K.; Deming, M. A.; Keung, W., Organometallics 2000, 19, 1166-1174.62. (a) Lunder, D. M.; Lobkovsky, E. B.; Streib, W. E.; Caulton, K. G., J. Am. Chem. Soc. 1991, 113, 1837-1838; (b) Johnson, T. J.; Folting, K.; Streib, W. E.; Martin, J. D.; Huffman, J. C.; Jackson, S. A.; Eisenstein, O.; Caulton, K. G., Inorg. Chem. 1995, 34, 488-499.

187In an inner sphere mechanism involving dissociation of the tethered-amine donor, the

alkoxide ligand in G labilizes the cis-amine ligand61 giving the 16 electron iridium(III) alkoxide

complex J with a decoordinated amine group (Scheme 6.10) The Ir–O bond length (1.91 Å) is

shorter in J in comparison to G (2.07 Å) to account for partial π-stabilization as observed

elsewhere.61-62 The free energy barrier for the labilization of the tethered amine donor by the

alkoxide ligand is 14.5 kcal/mol and it is entropically favoured (ΔS = 11.6 cal/mol·K). Complex

J then activates dihydrogen via oxidative addition to produce a dihydride63 complex (dH–H = 1.64

Å). Reductive elimination of the hydride and alkoxide releases the product alcohol. The substrate

ketone then coordinates and is attacked by the metal hydride in a four-membered ring transition

state 2a, 3a, 5c to give J again, with a free energy barrier of 20.5 kcal/mol comprised of an

unfavourable entropy change (ΔSǂ = 16.4 cal/mol·K). The transition state structure (TSM,J, Figure

6.19), was located on a very flat potential energy surface64 after numerous computational

attempts. It shows an electronegative carbon (APT charge = -0.68 ESU) of the coordinated

acetone and a charged hydride ligand (APT charge = -0.05 ESU).

Scheme 6.10. The Disfavoured Pathways Involving Either an η5 to η3 Ring Slip or a

Decoordination of the Amine Group Leading to the Activation of H2 by the Iridium(III) System.

In this mechanism, the N–H group does not play an active role in catalysis. However, a

comparison of the observed catalytic activities of 19 and 22 does not support this. The formation

of the hydride-amine complex 21 (or D) using H2 when either basic 2-propanol or THF is used as

the reaction medium could well proceed by only the outer sphere mechanism according to

63. Morris, R. H., Coord. Chem. Rev. 2008, 252, 2381-2394.64. (a) Bosch, E.; Moreno, M.; Lluch, J. M.; Bertran, J., Chem. Phys. Lett. 1989, 160, 543-548; (b) Koseki, S.; Gordon, M. S., J. Phys. Chem. 1989, 93, 118-125; (c) Espinosagarcia, J.; Corchado, J. C., J. Phys. Chem. 1995, 99, 8613-8616.

Ir NNN

CH3

H

OH

H

Decoordination ofNH2 group

+ H2

+ H2

Ring slippageof the Cp ring

∆ G‡ = 14.6 kcal/mol

∆ G‡ = 21.1 kcal/mol

NNN

CH3

H

Ir

OHH

∆ G = -1.7 kcal/mol GA

Ir

NN

N

CH3

HO

H

H

CH3NN

IrNH

H H O

J

CH3NN

IrN

OH HH

L

Ir

NN

N

CH3

HH O H

HH

N P

∆ G= 14.5 kcal/mol

∆ G= 40.4 kcal/mol

HH

+ +

+ +

++

188computations (ΔGǂ = 22.6 versus 38.3 kcal/mol relative to A, H2 and acetone for the activation

of H2 in the inner sphere mechanism).

Figure 6.19. Computed transition state structure for the attack of hydride on the coordinated

acetone (TSM,J) of the iridium(III) system for the inner sphere mechanism involving the

decoordination of the amine group. The bond lengths (Å) are given in the structure. The colour

code for the atoms are: iridium (yellow), nitrogen (blue), oxygen (red), carbon (grey) and

hydrogen (white).

6.3.17 Electronic Properties of Ruthenium(II) Complexes that Relate to their Reactivity in

Catalytic Hydrogenation. As the presence of an N-heterocyclic carbene provides enhanced

catalytic activity of the ruthenium(II) and iridium(I/III) system, we set out to prepare the

carbonyl complexes [RuCp*(C–NH2)(CO)]PF6 (23) and [RuCp*(P–NH2)(CO)]PF6 (24) in order to

compare their electronic properties. Both complexes 23 and 24 were characterized by NMR and

an X-ray diffraction study (Schemes 6.1 and 6.2, Figures 6.20 and 6.21) The carbonyl stretching

wavenumbers of 23 and 24 were observed at 1940 and 1952 cm-1, respectively.

189



(Å) and bond angles (deg): Ru(1)–C(1), 2.065(4); Ru(1)–N(3), 2.178(3); Ru(1)–C(22), 1.859(4);

Ru(1)–C(15), 2.223(4); C(22)–O(1), 1.149(5); C(1)–Ru(1)–N(3), 90.8(2); C(1)–Ru(1)–C(22),

95.1(2); C(22)–Ru(1)–N(3), 91.7(2).

A series of ruthenium(II) complexes formulated as RuCp*(D–NH2)Cl, where D is a donor

group, have been evaluated by Ikariya and co-workers by preparing the corresponding cationic

carbonyl complexes.6c, 65 The carbonyl stretching wavenumber of 23 lies in between those of the

complex [RuCp*(κ2(P,N)-PPh2CH2CH2NH2)CO]OTf, in which the D–NH2 ligand is less

donating, and complexes containing nitrogen donors, which are more electron donating (Figure

6.22). Of note, the complexes RuCp*(κ2(N,N)-N(CH3)2CH2CH2NH2)Cl and RuCp*(κ2(N,N)-(2'-

C5H4N) CH2NH2)Cl are ketones and aldehydes hydrogenation catalysts upon activation by KOH,

yet are poor catalysts for the hydrogenolysis of epoxides; the complex, RuCp*(κ2(P,N)-

PPh2CH2CH2NH2)Cl (16b), on the other hand, shows the reverse trend.20b, 24 Ikariya and co-

workers have attributed the stronger Brønsted acidity of the coordinated NH2 group of the latter

to the facile proton and hydride transfer to the polar bond.6c A counter-example to this is the

rhodium(I) amine complex, [Rh(η4-diene)(C–NHR)]BF4 (C–NHR = 1-mesityl-3-(2-

(mesitylamino)ethyl)imidazolylidene), which contains an aniline-type N–H group, is not active

towards the transfer hydrogenation of benzophenone.33c The phosphine-amine complex,

65. Ito, M., Pure Appl. Chem. 2008, 80, 1047-1053.

190[RuCp*(P–NH2)Py]PF6 (16a), is a poor catalyst for the hydrogenation of acetophenone when

activated by base.34 This P–NH2 ligand is the least donating in the series, judging from its

carbonyl stretching wavenumber in complex 24.



(Å) and bond angles (deg): Ru(1)–P(1), 2.320(1); Ru(1)–N(1), 2.166(4); Ru(1)–C(30), 1.877(6);

Ru(1)–C(24), 2.218(5); C(30)–O(1), 1.140(6); P(1)–Ru(1)–N(1), 87.3(1); P(1)–Ru(1)–C(30),

88.6(2); C(30)–Ru(1)–N(1), 90.8(2).

The chelation effect of the phosphine-amine ligand that forms a 5-membered or a 6-

membered ring including the metal may contribute to the difference in electronics at the metal

center.66 Overall, the hydricity of the hydride ligand that forms must also contribute to the

reactivity exhibited by these complexes;45, 67 and a good balance of the hydricity of the metal

hydride and the acidity of the protic amine group, which is dependent of the donor strength of the

D–NH2 ligand, is required to promote a successful transfer of H+/H- to the polar bond of interest,

and therefore, show high activity in catalysis.3a, 6b, 6c The rich substrate scope and the high

turnover frequencies of 15 as a hydrogenation catalyst (ketones, an epoxide, a ketimine and an

ester) suggests that a correct electronic balance is achieved in such a NHC-amine system in

contrast to its other counterparts.

66. Bassetti, M., Eur. J. Inorg. Chem. 2006, 4473-4482.67. Belkova, N. V.; Epstein, L. M.; Shubina, E. S., Eur. J. Inorg. Chem. 2010, 3555-3565.

191

Figure 6.22. The carbonyl stretching wavenumbers (cm-1 in KBr) of a series of ruthenium(II)

complexes, [RuCp*(D–NH2)CO]+, where D is a donor group.

6.4 Conclusion

A comparison of the activity and selectivity of two structurally similar ruthenium(II) (15) and

iridium(III) (19 and 21) catalyst systems in the H2-hydrogenation of ketones reveals that the

ruthenium system has the higher activity but with similar selectivity in comparison to the iridium

system in the hydrogenation of ketones. An alcohol-assisted outer sphere bifunctional

mechanism is proposed for both systems. There are several pieces of evidence to support this:

(a) the pronounced effect of alcohols in catalysis, and H/D scrambling that is observed when

deuterated sources are used;

(b) an N–H group is required by the chloride complex 19 for catalysis since the structurally

similar iridium(III) complex 22 with no N–H group is much less active;

(c) a low free energy barrier is calculated for the transfer of a proton/hydride couple from the

neutral ruthenium(II) hydride Ru(η5-Cp)(C–NH2)H to the ketone in the outer sphere; however,

the cationic hydride complex [Ir(η5-Cp)(C–NH2)H]+ is calculated to have a high barrier;

(d) an accessible energy barrier is calculated for the transfer a proton/hydride couple from the

neutral hydride complex Ir(η4-CpH)(C–NH2)H to acetone in the outer sphere;

(f) a significant decrease in the free energy barriers to the heterolytic splitting of the η2-H2

ligand on Ru(η5-Cp)(C–NH) and Ir(η4-CpH)(C–NH) is calculated when a 2-propanol molecule

acts a proton shuttle by participating in a six-membered ring transition state.6c, 12e, 13a, 14b, 19b, 20b, 22

Ru

NN

N

CH3PF6OC

HH

RuPPh2N

PF6OC

HH

2423

Ru

N NOTfOC

HH

RuPPh2N

OTfOC

HH

RuN

N

OTfOC

HH

CO Stretch(cm-1, KBr)

1931 1938 1940 1948 1952

+ + + + +

192 The cationic charge of the intermediates of the iridium(III) system lead to a diminished

ability of the metal hydride-amine complex 21 to react with a ketone in the absence of base. The

neutral, well-defined complexes containing a cyclometalated C–NH2 ligand and an anionic

carbon donor, IrCp*(κ2(C,N)-2-C6H4CR2NH2)H49 and Ru(η6-C6H6)(κ2(C,N)-2-C6H4CR2NH2)H,50

react with acetophenone in the absence of base. The decreased hydricity of such piano-stool

cationic metal hydrides in catalysis appears to be a general phenomenon.45, 67

The activation of the iridium(III) hydride-amine complex 21 by alkoxide base seems to be

crucial for catalysis. Our computational studies support the proposal that the base deprotonates

the amine group of the cationic hydride-amine complex 21 and this then triggers the migration of

the hydride to the η5-Cp ring producing a neutral iridium(I) amido complex. This amido complex

with an η4-cyclopentadiene (CpH) group splits η2-H2 with the assistance of alcohol to produce the

Ir–H/N–H couple required for the outer sphere hydrogenation of ketones in the bifunctional

mechanism. These steps involve novel iridium(I) intermediates and proceed with reasonable free

energy barriers. The two other possibilities, which are the reductive elimination of 2-propanol

and the ring slippage pathway, are characterized by a high energy barrier to transfer the metal

hydride to the ketone in the outer sphere within the catalytic cycle in comparison to our proposed

mechanism. As experimental evidence supports the role of the N–H group, the reductive

elimination pathway is not feasible as this involves the decoordination of the amine throughout

the catalytic cycle. Although the migration of the hydride ligand to the η5-Cp* ligand is not

common but is precedented,42b, 56b, 56c this might be favoured by the presence of the unique NHC

ligand in our catalytic system.28b, 28c It appears that the activation of the cationic hydride-amine

complex 21 is responsible for the poor activity of the iridium(III) system for catalytic ketone

hydrogenation in comparison to its ruthenium(II) counterpart.

This role of the alkoxide base in the catalysis should be considered for other systems

involving catalytic ketone hydrogenation. Although it has been suggested that the alkali metal

cations of these bases may play a crucial role to stabilize the transition state during hydride

transfer to the ketone,51 we have found that the alkoxide base reacts with the metal hydride

complex by changing the geometry and the electronics of the piano-stool complex in order to

make it reactive. It was known that certain ruthenium(II)-based catalysts required a high base

loading (C/B > 1/1000) in the hydrogenation of ketones using H2.14b, 68 The role of the alkoxide

68. Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R., Angew. Chem. Int. Ed. 1998, 37, 1703-1707.

193base remains unclear but it may play a similar role to transform the metal hydride complex to a

more reactive species which activates hydrogen and promotes H+/H- transfer to the ketone.

Finally, the donor ability of the D–NH2 type ligand (D = NHC, phosphine, amine, 2'-pyridine)

was also investigated by use of the carbonyl stretching wavenumbers of the complexes

[RuCp*(D–NH2)CO]X to help explain the poorer performance in the catalytic H2-hydrogenation

of ketones of the phosphine-amine complexes [RuCp*(P–NH2)py]PF6 (16a) and [IrCp*(P–

NH2)Cl]PF6 (20) compared to C–NH2 analogues. The C–NH2 ligand was found to be more

donating than the P–NH2 ligand.

We conclude that a fine-tuning of the Brønsted acidities of the N–H and the M–H groups by

choosing the right donor ligand, the right metal center, as well as the correct overall charge of the

catalyst is crucial to maximize the activity for the hydrogenation of polar bonds. The present

study will provide guidelines in catalyst architecture and in the rational use of alkoxide base to

maximize the potential of bifunctional catalysts in the direct hydrogenation of polar bonds.



carried out under a nitrogen or argon atmosphere using standard Schlenk-line and glovebox

techniques. Dry and oxygen-free solvents were always used. The syntheses of bis[1-(2-

aminomethylphenyl)-3-methylimidazol-2-ylidene]nickel(II) hexafluorophosphate (12) and [1-(2-

aminomethylphenyl)-3-methylimidazol-2-ylidene](η5-pentamethylcyclopentadienyl)-

(pyridine)ruthenium(II) hexafluorophosphate (15) have been reported previously.31, 34 The

syntheses of RuCp*(cod)Cl,69 [IrCp*Cl2]2,70 2-(diphenylphosphino)benzylamine (P–NH2),71 and 1-

(N,N-dimethylamino)propyl-3-methylimidazolium chloride hydrochloride (1g)46 were reported in

the literature. All other reagents and solvents were purchased from commercial sources and

were used as received. Deuterated solvents were purchased from Cambridge Isotope

Laboratories and Sigma Aldrich and degassed and dried over activated molecular sieves prior to

use. NMR spectra were recorded on a Varian 400 spectrometer operating at 400 MHz for 1H, 100

MHz for 13C, 161 MHz for 31P and 376 MHz for 19F. The 1H and 13C{1H} NMR were measured

69. Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Zhao, H. T.; Lin, Z. Y.; Jia, G. C.; Fokin, V. V., J. Am. Chem. Soc. 2008, 130, 8923-8930.70. White, C.; Yates, A.; Maitlis, P. M., Inorg. Synth. 1992, 29, 228-234.71. Cahill, J. P.; Bohnen, F. M.; Goddard, R.; Kruger, C.; Guiry, P. J., Tetrahedron: Asymmetry 1998, 9, 3831-3839.

194relative to partially deuterated solvent peaks but are reported relative to tetramethylsilane (TMS).

All 19F chemical shifts were measured relative to trichlorofluoromethane as an external reference.

All 31P chemical shifts were measured relative to 85% phosphoric acid as an external reference.

All infrared spectra were recorded on a Nicolet 550 Magna-IR spectrometer. The elemental

analysis was performed at the Department of Chemistry, University of Toronto, on a Perkin-

Elmer 2400 CHN elemental analyzer. Samples were handled under argon where it was


diffractometer with Mo Kα radiation (λ = 0.71073 Å). The CCD data were integrated and scaled


Refinement was by full-matrix least-squares on F2 using all data.

6.5.2 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene]-chloro-(η5-penta-

methylcyclopentadienyl)iridium(III) Hexafluorophosphate ([IrCp*(C–NH2)Cl]PF6, 19). A

Schlenk flask was charged with 12 (71 mg, 0.098 mmol) and [IrCp*Cl2]2 (78 mg, 0.098 mmol).

Dry acetonitrile (12 mL) was added to the reaction mixture, and it was refluxed under an argon

atmosphere for 2.5 h until a deep green solution was obtained. The solvent was evaporated under

reduced pressure, and the residue was extracted with tetrahydrofuran (4 mL) and filtered through

a pad of Celite under a nitrogen atmosphere. Addition of diethyl ether (15 mL) to this and slow

cooling of the solution at -25°C afforded a yellow precipitate. This was collected on a glass frit,

washed with diethyl ether (1 mL) and dried in vacuo. Yield: 127 mg, 93%. Suitable crystals for

an X-ray diffraction study were obtained by slow diffusion of diethyl ether into a saturated solu-

tion of 19 in acetonitrile under a nitrogen atmosphere. 1H NMR (CD2Cl2, δ): 7.75 (dd, JHH = 1.70,

7.32 Hz, 3-CH of Ph, 1H), 7.59 (m, 4-CH and 5-CH of Ph, 2H), 7.48 (dd, JHH = 1.51, 7.55 Hz, 6-

CH of Ph, 1H), 7.34 (d, JHH = 2.06 Hz, 5-CH of imid.,1H), 7.32 (d, JHH = 2.06 Hz, 4-CH of imid.,

1H), 4.38 (br, CH2 and NH2, 3H), 4.04 (s, CH3, 3H), 3.29 (m, CH2, 1H), 1.33 (s, CH3 of Cp*,

15H). 19F NMR (CD2Cl2, δ): -72.2 (d, JPF = 712 Hz). 13C{1H} NMR (CD2Cl2, δ): 155.8 (Ir–C),

139.1 (CPh), 132.7 (CPh), 131.5 (CPh), 130.9 (CPh), 130.1 (CPh), 125.8 (CPh), 125.4 (Cimid.), 124.2

(Cimid.), 90.5 (CAr-Cp*), 47.4 (CH2), 38.9 (CH3), 8.6 (CH3 of Cp*). MS (ESI, methanol/water; m/z):

550.2 ([M]+), 514.2 ([M – Cl]+). HRMS (ESI, methanol/water; m/z): calcd for C21H28N3ClIr+ ([M]

+): 550.1595, found: 550.1566. Anal. Calcd for C21H28N3ClF6PIr: C, 36.29; H, 4.06; N, 6.05.

Found: C, 36.72; H, 3.97; N, 5.23.

6.5.3 Synthesis of [2-(Diphenylphosphino)benzylamine]-chloro-(η5-pentamethyl-cyclo-

pentadienyl)iridium(III) Hexafluorophosphate ([IrCp*(P–NH2)Cl]PF6, 20). A scintillation

195vial with a threaded screw cap was charged with [IrCp*Cl2]2 (47 mg, 0.059 mmol) in dry di-

chloromethane (6 mL) under a nitrogen atmosphere. A solution of 2-(diphenylphosphino)-ben-

zylamine (36 mg, 0.12 mmol) in dry dichloromethane (6 mL) was added to the aforementioned

yellow solution and stirred for 1 h at room temperature (25oC). Silver hexafluorophosphate (30

mg, 0.12 mmol) in dry acetonitrile (1 mL) was added to the reaction mixture, and a pale-yellow

suspension was obtained. After stirring the reaction mixture further for 0.5 h, it was filtered

through a pad of Celite under a nitrogen atmosphere. The solvent was removed at reduced pres-

sure. The yellow crude product was recrystallized with dichloromethane (2 mL) and a diethyl

ether and pentane mixture (1:8, 12 mL) to yield a yellow solid, which was filtered and dried in

vacuo. Yield: 54 mg, 57%. Suitable crystals for an X-ray diffraction study were obtained by slow

diffusion of diethyl ether into a saturated solution of 20 in dichloromethane under a nitrogen at-

mosphere. 1H NMR (CD2Cl2, δ): 7.76 (m, Ar-CH of PPh2, 2H), 7.59 (m, Ar-CH of PPh2, 8H),

7.44 (m, 3-CH of Ph, 1H), 7.38 (m, 4-CH and 5-CH of Ph, 2H), 7.22 (m, 6-CH of Ph, 1H), 5.52

(br, NH2, 1H), 4.39 (m, CH2, 1H), 3.73 (m, br, CH2 and NH2, 2H), 1.55 (s, CH3 of Cp*, 15H). 19F

NMR (CD2Cl2, δ): -72.3 (d, JPF = 712 Hz). 31P{1H} NMR (CD2Cl2, δ): 4.5 (s), -144.4 (sept, JPF =

712 Hz). 13C{1H} NMR (CD2Cl2, δ): 138.5 (d, JCP = 13.62 Hz, CPPh), 135.4 (d, JCP = 12.07 Hz,

CPPh), 134.3 (d, JCP = 9.54 Hz, CPPh), 132.8 (d, JCP = 2.54 Hz, CPPh), 132.3 (d, JCP = 2.69 Hz, CPPh),

131.8 (CPh), 131.7 (CPh), 131.6 (d, JCP = 2.42 Hz, CPh), 131.0 (d, JCP = 2.36 Hz, CPh), 130.8 (d, JCP

= 55.83 Hz, CPPh), 129.6 (d, JCP = 10.96 Hz, CPh), 129.0 (d, JCP = 11.08 Hz, CPh), 127.5 (d, JCP =

60.80 Hz, CPPh), 124.8 (d, JCP = 56.53 Hz, CPPh), 94.5 (CAr-Cp*), 48.8, (d, JCP = 11.00 Hz, CH2), 8.8

(CH3 of Cp*). MS (ESI, methanol/water; m/z): 654.2 ([M]+), 618.2 ([M – Cl]+). HRMS (ESI,

methanol/water; m/z): calcd for C29H33NPClIr+ ([M]+): 654.1663, found: 654.1638. Anal. Calcd

for C29H33NClF6P2Ir: C, 43.58; H, 4.16; N, 1.75. Found: C, 43.11; H, 4.11; N, 1.79.

6.5.4 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene]-hydrido-(η5-pen-

tamethylcyclopentadienyl)iridium(III) Hexafluorophosphate ([IrCp*(C–NH2)H]PF6, 21). A

Schlenk flask was charged with 19 (50 mg, 0.072 mmol) in 2-propanol solution (14 mL). The

solution was warmed to 50°C under an argon atmosphere. A solution of sodium 2-propoxide (18

mg, 0.22 mmol) in 2-propanol (6 mL) was added to this stirring solution during a course of 0.5 h,

whereupon the color of the reaction mixture turned from yellow to red, then to deep brown. The

solution was stirred for a further 3 h. After the reaction had gone to completion, the solvent was

removed under vacuum. The solid residue was extracted with THF (4 mL) and filtered through a

pad of Celite. The addition of pentane (16 mL) to the THF solution yielded a beige-coloured pre-

196cipitate, which was collected and dried in vacuo. Yield: 36 mg, 76%. Suitable crystals for an X-

ray diffraction study were obtained by slow diffusion of diethyl ether into a saturated solution of

21 in THF under a nitrogen atmosphere at -30°C. 1H NMR (CD3CN, δ): 7.60 (m, 3-CH and 4-CH

of Ph, 2H), 7.53 (m, 5-CH of Ph, 1H), 7.49 (m, 6-CH of Ph, 1H), 7.37 (d, JHH = 2.13 Hz, 5-CH of

imid.,1H), 7.34 (d, JHH = 2.13 Hz, 4-CH of imid., 1H), 4.80 (br, NH2, 1H), 4.01 (m, CH2, 1H),

3.73 (s, CH3, 3H), 3.55 (br, NH2, 1H), 2.85 (dt, JHH = 3.50, 12.40 Hz, CH2, 1H), 1.51 (s, CH3 of

Cp*, 15H), -13.59 (s, Ir–H, 1H). 19F NMR (CD3CN, δ): -73.0 (d, JPF = 706 Hz). 13C{1H} NMR

(CD3CN, δ): 157.0 (Ir–C), 140.8 (CPh), 133.0 (CPh), 132.5 (CPh), 130.6 (CPh), 129.4 (CPh), 126.4

(CPh), 123.8 (Cimid.), 123.5 (Cimid.), 90.6 (CAr-Cp*), 49.2 (CH2), 39.6 (CH3), 9.8 (CH3 of Cp*). IR

(KBr, cm-1): 2068 (v(Ir–H)). MS (ESI, methanol/water; m/z): 516.2 ([M]+). HRMS (ESI, meth-

anol/water; m/z): calcd for C21H29N3ClIr+ ([M]+): 516.1985, found: 516.1961. Anal. Calcd for

C21H29N3F6PIr: C, 38.18; H, 4.42; N, 6.36. Found: C, 38.02; H, 4.35; N, 6.01.

6.5.5 Synthesis of [1-(N,N-Dimethylaminopropyl)-3-methylimidazol-2-ylidene]-chloro-(η5-

pentamethylcyclopentadienyl)iridium(III) Hexafluorophosphate ([IrCp*(C–NMe2)Cl]PF6,

22). A Schlenk flask was charged with silver(I) oxide (65 mg, 0.28 mmol) and [IrCp*Cl2]2 (75

mg, 0.094 mmol) in dry acetonitrile (8 mL) under molecular sieves (3 Å). In a separate Schlenk

flask was charged with 1g (45 mg, 0.19 mmol) and anhydrous dimethyl sulfoxide (DMSO, 3

mL) under an argon atmosphere. The DMSO solution containing the dissolved imidazolium salt

was then added to the stirring solution of silver(I) oxide and [IrCp*Cl2]2 in acetonitrile. Acetoni-

trile washing (4 mL) was applied to the residual DMSO containing the imidazolium salt, and this

was also added to the reaction mixture. This was stirred under an argon atmosphere at room tem-

perature (25°C) for overnight. After the reaction has gone to completion, the reaction mixture

was filtered through a pad of Celite under an argon atmosphere. The solvent was evaporated un-

der reduced pressure. The residue that obtained was washed with toluene (6 mL) and then diethyl

ether (8 mL). It was dissolved in a dichloromethane and acetonitrile mixture (1:1, 10 mL) and

this was added silver hexafluorophosphate (47 mg, 0.19 mmol) and stirred further for 1 h. The

suspension that formed was filtered through a pad of Celite. The solvent was evaporated under

reduced pressure, and the residue that obtained was precipitated from tetrahydrofuran (3 mL) and

pentane (15 mL). This was filtered and dried in vacuo to give a bright yellow solid. Yield: 77

mg, 61%. Suitable crystals for an X-ray diffraction study were obtained by slow diffusion of di-

ethyl ether into a saturated of 22 in dichloromethane under a nitrogen atmosphere 1H NMR

(CD2Cl2, δ): 7.17 (d, JHH = 2.00 Hz, 5-CH of imid., 1H), 7.06 (d, JHH = 2.00 Hz, 4-CH of imid.,

1971H), 4.28 (m, CH2, 1H), 4.18 (m, CH2, 1H), 3.92 (s, CH3, 3H), 3.49 (t, JHH = 13.12 Hz, CH2, 1H),

3.24 (m, CH2, 1H), 2.21 (t, JHH = 13.41 Hz, CH2, 2H), 1.70 (s, CH3 of N(CH3)2, 6H), 1.56 (s, CH3

of Cp*, 15H). 19F NMR (CD2Cl2, δ): -73.1 (d, JPF = 711 Hz). 13C{1H} NMR (CD2Cl2, δ): 155.4

(Ir–C), 124.6 (Cimid.), 124.3 (Cimid.), 91.6 (CAr-Cp*), 69.8 (CH2), 49.3 (CH2), 38.7 (CH3), 26.8 (CH2),

9.9 (CH3 of Cp*), 8.8 (CH3 of N(CH3)2). MS (ESI, methanol/water; m/z): 496.2 ([M – Cl]·+),

451.2 ([M – Cl – NMe2]·+). Anal. Calcd for C19H32N3ClF6 PIr: C, 33.80; H, 4.78; N, 6.22. Found:

C, 33.96; H, 4.74; N, 6.34.

6.5.6 Synthesis of [1-(2-Aminomethylphenyl)-3-methylimidazol-2-ylidene]-carbonyl-(η5-

pentamethylcyclopentadienyl)ruthenium(II) Hexafluorophosphate ([RuCp*(C–NH2)

(CO)]PF6, 23). A Schlenk flask was charged with 15 (32 mg, 0.049 mmol). It was evacuated and

backfilled with a CO atmosphere (1 atm) for two times. A solution of tetrahydrofuran (10 mL)

saturated with Ar was injected into the Schlenk flask against a flow of CO by means of a syringe

and a needle. The colour of the solution turned immediately from orange-yellow to pale yellow

upon dissolution. The solution was stirred at room temperature (25°C) for 3 h. The volume of the

solvent was reduced (2 mL). Addition of diethyl ether or hexanes (12 mL) to this and slow cool-

ing of the solution at -25°C afforded a pale yellow crystalline solid, which was filtered on a glass

frit and dried in vacuo. Yield: 22 mg, 75%. Suitable crystals for an X-ray diffraction study were

obtained by slow diffusion of hexanes into a saturated solution of 23 in THF under a nitrogen at-

mosphere. 1H NMR (CD2Cl2, δ): 7.62 (m, 3-CH and 5-CH of Ph, 2H), 7.51 (m, 4-CH and 6-CH

of Ph, 2H), 7.35 (d, JHH = 2.07 Hz, 5-CH of imid.,1H), 7.29 (d, JHH = 2.07 Hz, 4-CH of imid.,

1H), 4.21 (td, JHH = 2.69, 11.53 Hz, CH2, 1H), 3.89 (s, CH3, 3H), 3.84 (br, NH2, 1H), 2.98 (m,

CH2, 1H), 2.17 (m, br, NH2, 1H), 1.40 (s, CH3 of Cp*, 15H). 19F NMR (CD2Cl2, δ): -72.5 (d, JPF =

712 Hz). 13C{1H} NMR (CD2Cl2, δ): 207.1 (Ru–CCO), 181.8 (Ru–C), 139.5 (CPh), 132.6 (CPh),

131.8 (CPh), 130.5 (CPh), 129.7 (CPh), 126.2 (CPh), 125.0 (Cimid.), 124.7 (Cimid.), 94.6 (CAr-Cp*), 48.9

(CH2), 39.4 (CH3), 9.5 (CH3 of Cp*). IR (KBr, cm-1): 1940 (v(CO)). MS (ESI, methanol/water;

m/z): 452.1 ([M]+). HRMS (ESI, methanol/water; m/z): calcd for C22H28N3ORu+ ([M]+): 452.1270,

found: 452.1269. Attempts at elemental analyses failed to give an acceptable carbon content,

while hydrogen and nitrogen content are in the acceptable range. Typical results: Anal. Calcd for

C22H38F6N3OPRu: C, 44.30; H, 4.73; N, 7.04. Found: C, 42.99; H, 4.64; N, 7.35.

6.5.7 Synthesis of [2-(Diphenylphosphino)benzylamine]-carbonyl-(η5-pentamethyl-cyclo-

pentadienyl)ruthenium(II) Hexafluorophosphate ([RuCp*(P–NH2)(CO)]PF6, 24). A scintilla-

tion vial with a threaded screw cap was charged with RuCp*(cod)Cl (50 mg, 0.13 mmol) in dry

198dichloromethane (5 mL) under a nitrogen atmosphere. A solution of 2-(diphenyl-phosphino)ben-

zylamine (40 mg, 0.13 mmol) in dry dichloromethane (5 mL) was added to the aforementioned

yellow solution and stirred for 1 h at room temperature (25°C), whereupon the reaction mixture

turned into orange in colour. Silver hexafluorophosphate (33 mg, 0.13 mmol) in dry acetonitrile

(1 mL) was added to the reaction mixture, and a yellow-brown suspension was obtained. After

stirring the reaction mixture for 0.5 h, it was filtered through a pad of Celite, and the solvent was

collected into a Schlenk flask under a nitrogen atmosphere. The solvent was then removed under

reduced pressure. The Schlenk flask containing the residue was evacuated and backfilled with a

CO atmosphere (1 atm) for two times. A solution of tetrahydrofuran (10 mL) saturated with Ar

was injected into the Schlenk flask against a flow of CO by means of a syringe and needle. The

colour of the solution turned immediately from orange-yellow to pale yellow upon dissolution.

The solution was stirred at room temperature for 3 h. The volume of the solvent was reduced (2

mL). Addition of diethyl ether (15 mL) afforded a yellow precipitate, which was filtered and

dried in vacuo to give a pale-yellow solid. Yield: 72 mg, 78%. Suitable crystals for an X-ray dif-

fraction study were obtained by slow diffusion of diethyl ether into a saturated solution of 24 in

dichloromethane under a nitrogen atmosphere. 1H NMR (CD2Cl2, δ): 7.56-7.49 (m, Ar-CH of Ph-

PPh2, 6H), 7.47 (m, Ar-CH of Ph-PPh2, 1H), 7.45-7.36 (m, Ar-CH of Ph-PPh2, 5H), 7.32-7.25 (m,

Ar-CH of Ph-PPh2, 2H), 4.00 (m, CH2, 1H), 3.71 (br, NH2, 1H), 3.58 (m, CH2, 1H), 3.05 (br,

NH2, 1H), 1.67 (s, CH3 of Cp*, 15H). 19F NMR (CD2Cl2, δ): -72.6 (d, JPF = 712 Hz). 31P{1H}

NMR (CD2Cl2, δ): 42.1 (s), -144.5 (sept, JPF = 712 Hz). 13C{1H} NMR (CD2Cl2, δ): 203.9 (d, JCP

= 16.83 Hz, Ru–Cco), 140.7 (d, JCP = 15.08 Hz, CPh-PPh), 134.1 (d, JCP = 12.48 Hz, CPh-PPh), 133.4 (d,

JCP = 10.93 Hz, CPh-PPh), 132.5 (d, JCP = 22.03 Hz, CPh-PPh), 132.3 (d, JCP = 31.09 Hz, CPh-PPh), 131.8

(d, JCP = 2.20 Hz, CPh-PPh), 131.6 (d, JCP = 2.11 Hz, CPh-PPh), 131.4 (d, JCP = 2.51 Hz, CPh-PPh), 131.3

(CPh-PPh), 130.9 (d, JCP = 1.95 Hz, CPh-PPh), 129.7 (CPh-PPh), 129.4 (d, JCP = 10.38 Hz, CPh-PPh), 129.3

(d, JCP = 10.51 Hz, CPh-PPh), 129.1 (d, JCP = 7.11 Hz, CPh-PPh), 96.8 (d, JCP = 1.91 Hz, CAr-Cp*), 50.4,

(d, JCP = 9.41 Hz, CH2), 9.7 (CH3 of Cp*). IR (KBr, cm-1): 1952 (v(CO)). MS (ESI, methanol/wa-

ter; m/z): 556.1 ([M]+). HRMS (ESI, methanol/water; m/z): calcd for C30H33NOPRu+ ([M]+):

556.1337, found: 556.1355. Anal. Calcd for C30H33NF6OP2Ru: C, 51.43; H, 4.75; N, 2.00. Found:

C, 51.10; H, 4.70; N, 1.91.

6.5.8 Representative Stoichiometric Reaction Using High Pressure of H2. Complex 19 (5 mg,

7.2 µmol) and potassium tert-butoxide (10 mg, 0.089 mmol) were dissolved separately in THF (4

mL and 2 mL, respectively) under a nitrogen atmosphere. These solutions were taken up by

199means of two separate syringes and needles in a glovebox. The needles were stoppered and the

syringes were taken to the reactor. The solutions were then injected into the reactor against a

flow of hydrogen gas. The hydrogen gas was adjusted to 25 bar and the reaction mixture was

stirred at 50°C. After 3 h of reaction, the reactor was detached from the hydrogen source and a H2

pressure of 2-4 bar was maintained. The reactor was attached to a Schlenk-line and backfilled

with argon gas using standard Schlenk-line techniques. The reaction mixture was then

transferred to an empty Schlenk flask filled with argon by syringe and a needle and the solvent

was removed in vacuum. The residue was taken up in acetonitrile-d3 and filtered through a pad of

Celite, and a 1H NMR spectrum was measured.

6.5.9 Stoichiometric Reaction Using 19 and 1-Phenylethoxide. A solution of complex 19 (15

mg, 0.022 mmol) in THF (6 mL) was added potassium 1-phenylethoxide (5 mg, 0.031 mmol) in

THF (4 mL) under an argon atmosphere at 50°C. The reaction was stirred for 3 h and the solvent

was removed in vacuum. The residue was taken up in acetonitrile-d3 and filtered through a pad of

Celite, and a 1H NMR spectrum was measured. The 1H NMR spectrum was compared to

authentic samples of 19, 21 and acetophenone in acetonitrile-d3 and the conversion was

measured by comparing the integration of the methyl groups of each.

6.5.10 Catalysis. Oxygen-free tetrahydrofuran (THF) used for all of the catalytic runs was stirred

over sodium for 2-3 days under argon, and freshly distilled from sodium benzophenone ketyl

prior to use. Oxygen-free 2-propanol used for all catalytic runs was stirred over magnesium

turnings and a single chip of iodine for several hours under argon, and freshly distilled prior to

use. Acetophenone was vacuum distilled over phosphorus pentoxide (P2O5) and stored under

nitrogen prior to use. 2-Propanol-d1 (purchased from Cambridge Isotope Laboratories) and 1-

phenylethanol were vacuum-distilled, dried over activated molecular sieves, and stored under

nitrogen prior to use. D2 gas was purchased from Cambridge Isotope Laboratories. All of the

hydrogenation reactions were performed at constant pressures using a stainless steel 50 mL Parr

hydrogenation reactor. The temperature was maintained at 25 or 50°C using a constant

temperature water bath. The reactor was flushed several times with hydrogen gas at 2-4 bar prior

to the addition of catalyst and substrate, and base solutions.

In a typical run (Table 6.1, entry 1), catalyst 19 (3 mg, 4.3 µmol) and acetophenone (104 mg,

0.87 mmol), and potassium tert-butoxide (4 mg, 0.036 mmol) were dissolved in THF (4 mL and

2 mL, respectively) under a nitrogen atmosphere. The catalyst/substrate and base solutions were

200taken up by means of two separate syringes and needles in a glovebox. The needles were

stoppered and the syringes were taken to the reactor. The solutions were then injected into the

reactor against a flow of hydrogen gas. The hydrogen gas was adjusted to 25 bar. Small aliquots

of the reaction mixture were quickly withdrawn with a syringe and a needle under a flow of

hydrogen at timed intervals by venting the Parr reactor at reduced pressure. Alternatively, small

aliquots of the reaction mixture were sampled from a stainless steel sampling dip tube attached to

a modified Parr reactor. The dip tube was 30 cm in length with an inner diameter of 0.01 inches,

and a swing valve was attached to the end of the sampling tube. Other technical details were

previously reported.12l Two small aliquots of samples were thereby withdrawn quickly at timed

intervals by opening the swing valve, and the first two aliquots were discarded. All samples for

gas chromatography (GC) analyses were diluted to a total volume of approximately 0.75 mL

using oxygenated THF.

A Perkin–Elmer Clarus 400 chromatograph equipped with a chiral column (CP chirasil-Dex

CB 25 m x 2.5 mm) with an auto-sampling capability was used for GC analyses. Hydrogen was

used as the mobile phase at a column pressure of 5 psi with a split flow rate of 50 mL/min. The

injector temperature was 250°C, the FID temperature was 275°C and the oven temperature was

130°C. Retention times (tR/min) for acetophenone: 4.56; (R)-1-phenylethanol: 7.58; (S)-1-

phenylethanol: 8.03; benzophenone: 7.94; diphenylmethanol: 12.57. All of the conversions were

reported as an average of two GC runs. The reported conversions were reproducible.

2016.5.11 Computational Details. All density functional theory (DFT) calculations were performed

using the Gaussian 0372 and 0973 packages with the restricted hybrid mPW1PW91 functional.74

Ruthenium and iridium were treated with the SDD75 basis relativistic effective core potential and

an associated basis set. All other atoms were treated with the double-ζ basis set 6-31++G**

which includes diffuse functionals76 and additional p-orbitals on hydrogen as well as additional

d-orbitals on carbon, nitrogen and oxygen.77 All geometry optimization were conducted in the

gas phase, and the stationary points were characterized by normal mode analysis. Reported free

energies were obtained at 1 atm and 298 K using unscaled vibrational frequencies. All transition

states reported were found to have a single imaginary frequency. The calculated Atomic Polar

Tensor (APT) charges were used to reflect more accurately the charge distribution on each atom

under the derivative of dipole moments with respect to an applied external electric field.78

72. Frisch, M. J., et al., Gaussian 03, Revision C.02 ed; Gaussian Inc.: Wallingford, CT 2004. Full citation is given in the Appendix.73. Frisch, M. J., et al., Gaussian 09, Revision A.1; Gaussian Inc.: Wallingford, CT 2009. Full citation is given in the Appendix.74. (a) Burke, K.; Perdew, J. P.; Wang, Y., Electronic Density Functional Theory: Recent Progress and New Directions; Plenum: New York, 1997; (b) Adamo, C.; Barone, V., J. Chem. Phys. 1998, 108, 664-675.75. (a) Andrae, D.; Haussermann, U.; Dolg, M.; Stoll, H.; Preuss, H., Theor. Chim. Acta 1990, 77, 123-141; (b) Leininger, T.; Nicklass, A.; Stoll, H.; Dolg, M.; Schwerdtfeger, P., J. Chem. Phys. 1996, 105, 1052-1059.76. (a) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. V., J. Comput. Chem. 1983, 4, 294-301; (b) Lynch, B. J.; Zhao, Y.; Truhlar, D. G., J. Phys. Chem. A 2003, 107, 1384-1388.77. Frisch, M. J.; Pople, J. A.; Binkley, J. S., J. Chem. Phys. 1984, 80, 3265-3269.78. Cioslowski, J., J. Am. Chem. Soc. 1989, 111, 8333-8336.

202Chapter 7: Conclusions and Future Work

7.1 Conclusions

A library of unsymmetrical nitrile-functionalized imidazolium salts (1a-1f) were synthesized

starting from 2-cyanophenylimidazole. The reactions of these imidazolium salts with silver(I)

oxide yielded silver(I) carbene complexes containing nitrile-functionalized N-heterocyclic

carbenes (C–CN). The use of these N-heterocyclic carbene (NHC) complexes of silver(I) as a

carbene transfer reagent was demonstrated by the reaction of the fully characterized complex,

[Ag(C–CN)2]BF4 (2a), with [Rh(cod)Cl]2 and [Ru(p-cymene)Cl2]2 leading to the rhodium(I)

complex ([Rh(C–CN)(cod)]2(BF4)2 (3) and the ruthenium(II) complex [Ru(p-cymene)

(C–CN)Cl]2(BF4)2 (4). An X-ray diffraction study and the infrared spectra of these complexes

established that the nitrile nitrogen and the carbene carbon of such a C–CN ligand are bridged to

two different metal centers.

The nitrile functional group on these C–CN ligands is prone to hydrolysis under basic

conditions. For instance, we showed that hydrolysis of the cyanomethyl group of a C–CN ligand

occurred during the preparation of a silver(I) carbene complex starting from the imidazolium salt

1b, which has cyanomethyl and cyanophenyl groups. This leads to the first N-heterocyclic

carbene complex of silver(I) with a primary-amido donor. The selectivity in hydrolysis of

cyanomethyl group over the cyanophenyl group suggests the process must be mediated by silver

centers. In addition, we have observed hindered rotation about the C–N bond of the amide by

means of 1H NMR. This suggested that an interaction between the silver(I) center and the oxygen

of the amido-group was indeed present.

When the silver(I) carbene complex 2a was reacted with trans-PdCl2(CH3CN)2, this led to the

dimeric complex [(C–CN)2Pd(μ-Cl)2Pd(CH3CN)2](BF4)2 (5a), along with the trimetallic complex

5b as a side product when wet diethyl ether and acetonitrile were used as recrystallization

solvents. Interestingly, the solid state structure of 5b ([{Pd(CH3CN)2}3(C–N–N–C)](BF4)4)

reveals the presence of a novel C–N–N–C donor ligand providing two bridging imido nitrogens

to adjacent palladium(II) centers. This C–N–N–C ligand comprised of a central –N=C–O–C=N–

linkage, which was formed from the partial hydrolysis and condensation of the two nitrile groups

of two adjacent C–CN ligands.

203To further explore the coordination chemistry of the C–CN ligand on group 10 metals, the

Platinum(II) complex with 1,5-cyclooctadiene, chloro and the C–CN ligands ([Pt(C–CN)

(cod)Cl]BF4, 7) was prepared in a transmetalation reaction of the silver(I) complex 2a with

Pt(cod)Cl2. The reaction of methoxide with the coordinated diolefin ligand on 7 afforded the

neutral complex 8 (Pt(C–CN)(η1:η2-coe-OMe)Cl) and complex 9 ([Pt(C–CN)(η1:η2-coe-

OMe)CH3CN]BF4) upon removal of the chloro ligand. For comparison, the palladium(II)

analogue, complex 6, was independently prepared by direct transmetalation of 2a and [Pd(η1:η2-

coe-OMe(μ-Cl)]2. These complexes bearing the C–CN and 2-methoxycyclooct-5-enyl ligands

([M(C–CN)(η1:η2-coe-OMe)]+: 6, M = Pd; 9, M = Pt) exists in both monomeric and dimeric

forms depending the choice of recrystallization solvents. Bridging C–CN ligands were observed

in the dimeric form by 1H NMR and infrared spectroscopy. On the other hand, different amounts

of rotamers were observed, owing to the orientation of C–CN ligand relative to the 2-

methoxycyclooct-5-enyl ligand, and restricted rotation about the M–CCarbene bond caused by the

steric crowding of the 2-methoxycyclooct-5-enyl ligand by the C–CN ligand,.

We have developed a facile synthetic route to access a primary amino-functionalized N-

heterocyclic carbene (C–NH2). This was achieved by the reduction of a nitrile-functionalized

imidazolium salt in the presence of nickel(II) chloride under mild conditions. The resulting

nickel(II) complex, [Ni(C–NH2)2](PF6)2 (12), is an axially chiral square-planar complex, and the

use of enantiopure Δ-TRISPHAT anions as an NMR chiral shift reagent is particularly useful to

observe the diastereotopic ion pairs by 1H NMR in acetonitrile-d3. A novel transmetalation

reaction moved the chelating C–NH2 ligand from complex 12 to a variety of platinum group

metal precursor complexes, including those of ruthenium(II), osmium(II), and iridium(III),

yielding important catalysts for the hydrogenation of polar double bonds. The ruthenium(II) and

osmium(II) complexes, [M(p-cymene)(C–NH2)Cl]PF6 (13, M = Ru; 14, M = Os), upon activation

by potassium tert-butoxide (KOtBu) as the base are transfer hydrogenation catalysts for the

hydrogenation of acetophenone in basic 2-propanol at 75°C to give 1-phenylethanol. A maximum

turnover frequency (TOF) of up to 880 h-1 was achieved with the ruthenium(II) complex 13,

giving a conversion of 96% to 1-phenylethanol in 3 h.

In addition, this ruthenium(II) complex (13), upon activation by an excess KOtBu (up to 8

equiv with respect to 13), catalyzes the H2-hydrogenation of ketones in tetrahydrofuran (THF)

under 25 bar of H2 pressure at 50°C with a TOF of up to 461 h-1 and a maximum conversion of

99%. The mechanism of action was thereby investigated by kinetic studies using acetophenone

204as the model substrate, including the studies of kinetic isotope effects using D2 gas and

acetophenone-d3. The rate law is determined to be rate = kH[Ru]tot[H2]/(1 + Keq[ketone]). Our

kinetic studies results are consistent with the heterolytic splitting of dihydrogen at the active

ruthenium species as the rate-determining step. In competition with this reaction is the reversible

addition of acetophenone to the active species to give an enolate complex. The transfer to the

ketone of a hydride and proton equivalent that are produced in the heterolytic splitting reaction

yields the product in a fast, low activation barrier step.

The bifunctional ruthenium hydride-amine complex [Ru(p-cymene)(C–NH2)H]PF6 (17)

containing the Ru–H/N–H couple was prepared. This complex, however, showed no activity

under catalytic conditions unless when activated by a base. This hydride-amine complex is

believed to be the resting state in the transfer hydrogenation mechanism. In fact, this is a rare

example of a catalyst with an M–H and N–H grouping that fails to undergo bifunctional catalysis

using the “NH effect”. The outer-sphere mechanism involving bifunctional catalysis of ketone

reduction is thus disfavored according to experimental studies. This was further confirmed by

showing that an analogous complex with a tethered tertiary amine group (C–CMe2), [Ru(p-

cymene)(C–NMe2)Cl]PF6⋅1.5 DMSO (18, DMSO = dimethyl sulfoxide), has comparable activity

for the H2-hydrogenation of acetophenone. Computational studies also suggest a high energy

barrier for the concerted transfer of a H+/H- pair to the ketone compared to dihydrogen addition

and subsequent heterolytic splitting if an outer-sphere bifunctional mechanism is operative.

An alternative to the outer-sphere bifunctional mechanism is therefore proposed on the basis

of experimental and theoretical findings. First, complex 13, when activated, leads to a

ruthenium-alkoxide complex. The alkoxide ligand labilizes the cis-amine ligand which leads to

the decoordination of the amine group of the C–NH2 ligand. This provides a vacant site for the

coordination of dihydrogen. Catalysis then proceeds with the heterolytic splitting of dihydrogen

by the internal alkoxide base, and then hydride attacks the coordinated ketone in the inner

sphere. The computed energy barriers for the heterolytic splitting of H2 and the attack of a ketone

by a metal hydride in the inner coordination sphere are consistent with our experimental

findings.

The ruthenium(II) ([RuCp*(C–NH2)py]PF6, 15, Cp* = pentamethylcyclopentadienyl ligand, py

= pyridine) and iridium(III) ([IrCp*(C–NH2)Cl]PF6, 19) complexes were prepared from the

transmetalation reaction of the nickel(II) complex 12 with RuCp*(cod)Cl and [IrCp*Cl2]2,

205respectively. A comparison to the activity in H2-hydrogenation of ketones reveals that the

ruthenium system has the higher activity and selectivity than the iridium system. The

ruthenium(II) complex 15 has a rich substrate scope in the H2-hydrogenation of ketones, and this

also catalyzes the hydrogenation of an aromatic ester, a ketimine, and the hydrogenolysis of

styrene oxide. A high substrate to catalyst loadings (catalyst to substrate ratio up to 1/11500) can

be used in ketone hydrogenation, under very mild reaction conditions (8 bar of H2 pressure at

25°C) in basic THF or 2-propanol. A maximum TOF of 17300 h-1 was achieved in the

hydrogenation of acetophenone in 2-propanol. On the other hand, the iridium(III) complex 19

catalyzes the H2-hydrogenation of acetophenone and benzophenone at a higher temperature

(50°C) and H2 pressure (25 bar) in basic THF with a lower substrate to catalyst loading. The use

of an excess alkoxide base (KOtBu, up to 16 equiv with respect to complex 19) is required to

achieve complete reduction of acetophenone to 1-phenylethanol by H2 in 2-propanol at a higher

rate. The phosphine-amine (P–NH2) complexes, [RuCp*(P–NH2)py]PF6 (16a) and [IrCp*(P–

NH2)Cl]PF6 (20), are poorer catalysts in the H2-hydrogenation of ketones compared to their C–

NH2 analogues.

On the basis of experimental findings and theoretical calculations, we propose an alcohol-

assisted outer sphere bifunctional mechanism for both the ruthenium(II) and iridium(III) systems.

First, H/D scrambling in acetophenone and the product alcohol was observed in both systems

when deuterated sources (D2 and 2-propanol-d1) were used. Significantly, we found that an N-H

group is required by complex 19 for catalysis since the structurally similar iridium(III) complex

22 containing a C–NMe2 ligand with no N–H group is much less active. We have computed the

outer-sphere bifunctional mechanism using DFT methods for both ruthenium(II) and iridium(III)

systems. A significant decrease in the free energy barrier to the heterolytic splitting of the η2-H2

ligand on the model complex, Ru(η5-Cp)(C–NH), is calculated when a 2-propanol molecule acts

a proton shuttle by participating in a six-membered ring transition state. On the other hand, a low

free energy barrier is found for the transfer of a proton/hydride couple from the neural hydride-

amine complex, Ru(η5-Cp)(C–NH2)H to the ketone in the outer sphere; however, the cationic

hydride-amine complex [Ir(η5-Cp)(C–NH2)H]+ is calculated to have a high barrier. In fact, we

have prepared the iridium(III) hydride-amine complex, [IrCp*(C–NH2)H]PF6 (21), and this failed

to react with a ketone in the absence of base. The decreased hydricity of such piano-stool

cationic metal hydrides in catalysis appears to be a general phenomenon based on our findings.

206We also showed that the activation of the iridium(III) hydride-amine complex 21 by alkoxide

base is crucial for catalysis. Our computational studies support the proposal that the base

deprotonates the amine group of the cationic hydride-amine complex 21. This triggers the

migration of the hydride to the η5-Cp ring producing a neutral iridium(I) amido complex. This

amido complex with an η4-cyclopentadiene (CpH) group splits η2-H2 with the assistance of

alcohol to produce the model complex, Ir(η4-CpH)(C–NH2)H, which contains a Ir–H/N–H couple

required for the outer sphere hydrogenation of ketones in the bifunctional mechanism. These

steps involve novel iridium(I) intermediates and proceed with accessible free energy barriers.

We also studied the donor ability of the D–NH2 type ligand (D = NHC, phosphine, amine, 2'-

pyridine) by use of the carbonyl stretches of the complexes [RuCp*(D–NH2)CO]X to help

explain the poorer performance in the catalytic H2-hydrogenation of ketones of the phosphine-

amine (P–NH2) complexes of ruthenium(II) (16a) and iridium(III) (20) compared to their C–NH2

analogues. The C–NH2 ligand was found to be more donating than the P–NH2 ligand.

We conclude, based on our present work using a primary-amino functionalized N-

heterocyclic carbene ligand, a right balance of the Brønsted acidities of the N–H and the M–H

groups is crucial to maximize the activity for the hydrogenation of polar bonds. This is achieved

by choosing the right donor ligand, the right metal center, as well as the correct overall charge of

the catalyst system.

7.2 Future Work

The discovery of late transition metal catalyst systems containing primary-amino

functionalized N-heterocyclic carbene ligand (C–NH2) for ketone hydrogenation is proven to be

important in order to understand the “NH effect” in bifunctional catalysis. We showed that the

correct choice of ligand sets and the metal center can provide highly active catalysts. There are

several future research directions that can stem from this work. The effect of the steric properties

of the ligand on catalysis has not been studied in this work. A series of C–NH2 ligands that

contains different substituents on the imidazolylidene ring is worth exploring, and analogous

ruthenium(II) and iridium(III) complexes can be synthesized based on a similar transmetalation

reaction of the corresponding nickel(II) complex with the appropriate precursor complex. This

1. Satoh, T.; Suzuki, S.; Suzuki, Y.; Miyaji, Y.; Imai, Z., Tetrahedron Lett. 1969, 4555-4558.

207will require the expansion of the family of nitrile-functionalized imidazolium salts, including the

search for new synthetic routes leading to these imidazolium salts, and to extend the scope of the

nitrile-reduction reaction based on the use of nickel(II) chloride. In fact, the use of other first row

metals such as iron(II) and cobalt(III) halides should be of target as their utility as reducing

agents have been demonstrated in the reduction of aromatic nitriles to amines.1

The emergence of pincer-type ligands, in particular their use to introduce metal-ligand

cooperativity upon activation, has become a new direction of research. Milstein and co-workers

have showed that ruthenium(II)2 and iron(II)3 based systems containing P–N–P pincer type

ligands are useful in the hydrogenation of esters2 and organic carbonates,4 the synthesis of amides

from esters and amines,5 and the photochemical splitting of water.6 Some of our group members

have began to explore these areas. The reduction of the imidazolium salt 1b, which contains

cyanomethyl and cyanophenyl groups, and 1c, which contains a methylpyridine and cyanophenyl

groups, could lead to interesting pincer type ligands. This will provide a novel NHC based N–C–

N ligand containing primary amine donors when coordinated to late transition metals. The metal

complexes of these could be important for the aforementioned processes by demonstrating metal-

ligand cooperativity.

During the course of our study to the ketone hydrogenation mechanisms, we found that the

decoordination of the amine group of the C–NH2 ligand could be facile under catalytic

conditions. Further research could be directed to study the effect on catalysis of changing the

metal-chelate (-M–C–NH2-) ring size from a seven-membered ring to a six-membered ring.

Results using the ruthenium(II) based complex, [Ru(p-cymene)(C–6–NH2)Cl]PF6, show that this

is a more active transfer hydrogenation catalyst of ketones upon activation by an alkoxide base in

comparison to its seven-membered ring analogue (Figure 7.1, left).7 The ruthenium(II) complex

containing the pentamethylcyclopentadienyl ligand could be important and useful for the

hydrogenation of polar double bonds such as those of esters and amides (Figure 7.1, right). This

system can be used for dehydrogenative coupling reactions8 as well as in the activation of other

2. Milstein, D., Top. Catal. 2010, 53, 915-923.3. Langer, R.; Leitus, G.; Ben-David, Y.; Milstein, D., Angew. Chem. Int. Ed. 2011, 50, 2120-2124.4. Balaraman, E.; Gunanathan, C.; Zhang, J.; Shimon, L. J. W.; Milstein, D., Nat. Chem. 2011, 3, 609-614.5. Gnanaprakasam, B.; Milstein, D., J. Am Chem Soc. 2011, 133, 1682-1685.6. Kohl, S. W.; Weiner, L.; Schwartsburd, L.; Konstantinovski, L.; Shimon, L. J. W.; Ben-David, Y.; Iron, M. A.; Milstein, D., Science 2009, 324, 74-77.7. Ohara, H.; O, W. W. N.; Morris, R. H.; Lough, A. J., Mansucript in preparation.8. Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J., Dalton Trans. 2009, 753-762.9. Ikariya, T., Bull. Chem. Soc. Jpn. 2011, 84, 1-16.

208small molecules.9 As a well-defined synthetic route that is developed for this new class of amino-

functionalized imidazolium salts based on our study,7 chiral catalyst systems can be designed and

this will be important for the asymmetric hydrogenation of ketones and imines, which can

potentially utilize the bifunctional mechanism. Williams and Roland have reported the synthesis

of some chiral imidazolium salts with a primary10 or a secondary11 amine group, respectively.

The silver(I) complexes of secondary-amine functionalized NHC were isolated.11

Figure 7.1. The structures of ruthenium(II) complexes containing the C–NH2 ligand forming a

six-membered ring metal-chelate (-M–C–NH2-).

Our research results have showed that the ruthenium(II)12 and iron(II)13 based complexes

containing an amine- or imine-based tetradentate P–N–N–P ligands provide highly active

catalysts for the hydrogenation of ketones and nitriles. The N-heterocyclic cyclic carbene based

ligand containing such a C–N–N–C type donor ligand should be of target and this might even

exhibit higher activity in these hydrogenation reactions based on our findings (Figure 7.2). One

approach to access this class of ligand is a reaction of a 1,2-alkyl-dibromide with the nickel(II)

complex, [Ni(C–NH2)2](PF6)2, which could yield the amine-based tetradentate ligand of

nickel(II), [Ni(C–N–N–C)](PF6)2. The transmetalation reaction of this complex with the

appropriate ruthenium(II) and iron(II) sources should yield the desired complex. This class of

tetradentate ligands containing a chiral diamine backbone should be pursued as well as this will

lead to highly active asymmetric hydrogenation catalysts.

10. Moore, T.; Merzouk, M.; Williams, N., Synlett 2008, 21-24.11. (a) Alexandre, F.; Baltaze, J. P.; Roland, S.; Mangeney, P., J. Organomet. Chem. 2006, 691, 3498-3508; (b) Flahaut, A.; Roland, S.; Mangeney, P., Tetrahedron: Asymmetry 2007, 18, 229-236.12. (a) Li, T.; Bergner, I.; Haque, F. N.; Iuliis, M. Z.-D.; Song, D.; Morris, R. H., Organometallics 2007, 26, 5940-5949; (b) Li, T.; Churlaud, R.; Lough, A. J.; Abdur-Rashid, K.; Morris, R. H., Organometallics 2004, 23, 6239-6247.13. Morris, R. H., Chem. Soc. Rev. 2009, 38, 2282-2291.

PF6Ru

NN

N

CH3XHH

+

X = halides

Ru

NN

N

CH3ClHH

209

Figure 7.2. Proposed structure of an iron(II) complex containing a C–N–N–C type donor ligand.

We succeeded to replace a phosphine-amine ligand (P–NH2) with a C–NH2 ligand in second

and third row transition metals-based ketone hydrogenation catalysts to achieve green catalysis.

New research directions for an even greener catalyst system should be sought by using first row

transition metal ions including those of iron(II), cobalt(II) and cobalt(III). These closely

resembles those of their ruthenium(II) and iridium(III) analogues, and could be beneficial for

catalysis. These systems will open new reaction opportunities other than the hydrogenation of

polar double bonds, and studies to the mechanism of actions of these systems could lead to

unexplored metal-ligand cooperativity.

FeNN

N

R

NN

N

R

n n

Ph PhBr

CO

2+

n = 0, 1

210Appendix

Table A.1. The oven temperatures, retention times (tR, tp, /min) for all of the substrates and

alcohol products reported from GC analyses.

Substrates/Alcohol Products Oven Temperature

(°C)

tR(min) tP(min)

130 4.56 7.58, 8.03

145 4.63 10.34, 12.16

140 6.46 14.81, 16.05

145 5.96 11.03, 12.09

155 7.02 12.79, 13.72

140 10.61 13.50, 14.28

140 5.19 10.06 (rac)

140 5.67 13.15, 13.78

170 9.67 14.43, 14.76

180 7.94 12.57

60 5.62 17.64, 18.79

130 3.53 7.31

130 4.81, 4.95 8.15, 8.65; 9.47

140 3.83 5.70, 5.93(tridecane)

O

O

O

O

O

Cl

Cl

Cl

Br

OOCH3

HO

HOCl

HOCl

HOCl

HOBr

HOOCH3

O

O

HO

HO

HO

HO

O

H

O

O

HO

O

O

O HO

O

HOHO

HO

211Derivation of the Rate Law (eq 5.1, Chapter 5)

Note that:

2 2 -2[alcohol]rate [Ru-H ][ketone] - [Ru-A][alcohol]d k k

dt= = ;

eq[Ru-B]=

[Ru-A][ketone]K ;

tot 2[Ru] = [Ru-A] + [Ru-B] + [Ru(H )]

RuCl NNN

CH3

HH

PF6

13

+

[Ru](H+)

O

H H

O

O

-[Ru]

+

Keq

k1 + H2 [Ru](H+)

H

KOtBu+

(Ru-B)

(Ru-A)

O+

k-1

[Ru]

(Ru-A)

k2

k-2 OH+

H

(Ru(H2))

k1k-1

Ru-A + H2 Ru(H2)

k2k -2

Ru(H2) + ketone Ru-A + alcohol

K eqRu-A + ketone Ru-B

212By steady state approximation:

21 2 -1 2 -2 2 2

1 2 -2 2 -1 2

-1 22

1 2 -2

[Ru(H )] [Ru-A][H ] - [Ru(H )] + [Ru-A][alcohol] - [Ru(H )][ketone] 0

[Ru-A]( [H ]+ [alcohol]) - [Ru(H )]( + [ketone]) 0

+ [ketone][Ru-A] = [Ru(H )][H ]+ [alcohol]

d k k k kdt

k k k k

k kk k

= ≈

=

As well,

tot eq 2

eq 2

[Ru] = [Ru-A] + [Ru-A][ketone] + [Ru(H )]

= [Ru-A](1 + [ketone]) + [Ru(H )]

KK

Hence,

tot 1 2 -22

-1 2 eq 1 2 -2

[Ru] ( [H ]+ [alcohol])[Ru(H )] = ( + [ketone])(1 + [ketone]) + [H ]+ [alcohol]

k kk k K k k

tot -1 2

-1 2 eq 1 2 -2

[Ru] ( + [ketone])[Ru-A] = ( + [ketone])(1 + [ketone]) + [H ]+ [alcohol]

k kk k K k k

The rate law, expressed in terms of [Ru]tot, will be:

2 tot 1 2 -2 -2 tot -1 2

-1 2 eq 1 2 -2

tot 1 2 2 -1 -2

-1

[Ru] [ketone]( [H ]+ [alcohol])- [Ru] [alcohol]( + [ketone])[alcohol]rate( + [ketone])(1 + [ketone]) + [H ]+ [alcohol]

[Ru] ( [H ][ketone]- [alcohol])+

k k k k k kddt k k K k k

k k k kk

= =

=1 2 -2 2 -1 eq 2 eq

[H ] + [alcohol] + [ketone]( + [ketone]) k k k k K k K+

For initial rates measurement, [alcohol] ~ 0, then:

1 2 tot 2

-1 1 2 2 -1 eq 2 eq

[Ru] [H ][ketone]rate + [H ] + [ketone]( + [ketone])

k kk k k k K k K

=+

213

If -1 1 2 2 -1 eq 2 eq 2+ [H ] << [ketone]( + [ketone]), as [H ] << [ketone]k k k k K k K+ , then:

1 2 tot 2

2 -1 eq 2 eq

1 tot 2

-1eq

2

[Ru] [H ][ketone] rate [ketone]( + [ketone])

[Ru] [H ]

1+ [ketone] eq

k kk k K k K

kk K

Kk

=+

=+

If -1 eq

2

0k K

k: when -1 eq 2k K k= , in which k2 is the rate constant that represents the fastest step

during catalysis, i.e. not rate determining, this gives:

H tot 2

eq

[Ru] [H ] rate (5.1) 1 [ketone]

kK

=+

214Complete Citation for Gaussian 03 and 09 Packages

Gaussian 03:

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;

Zakrzewski, V. G.; Montgomery, J. A. J.; E., S. R.; Burant, J.; C.; Dapprich, S.; Millam, J. M.;

Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.;

Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.;

Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;

Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;

Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;

Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.;

Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03,

Revision C.02 ed; Gaussian Inc.: Wallingford, CT, 2004.

Gaussian 09:

Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;

Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.;

Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.;

Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.;

Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.;

Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;

Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene,

M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.

E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;

Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.;

Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J., Gaussian 09,

Revision A.1; Gaussian Inc.: Wallingford, CT, 2009.

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