interaction of organic radicals with transition · pdf file!-carbonyl radicals metal-radical...

Chris Prier

MacMillan Group Meeting

March 23, 2011

Interaction of Organic Radicals with Transition Metals

IrICOPPh3Cl

Ph3P R•IrII

COPPh3Cl

Ph3PR

IrIIICOPPh3Cl

Ph3PRRX

X

R•


oxidation of alkyl radicals

CH3CH2•H2C=CH2

CH3CH2X

CuII

radical mechanism ofoxidative addition !-carbonyl radicals

metal-radical interactionsin asymmetric catalysis coenzyme vitamin B12

L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

R• MnXm

addition to the metalR Mn+1Xm

ligand transferR X Mn-1Xm-1

electron transferR± Mn±1Xm

! What are the mechanisms by which an alkyl radical can interact with a transition metal?

Kochi, J. K. Science. 1967, 27, 415-424.

Transition Metals and Organic Radicals

! Different CuII sources show divergent reactivity with respect to ethyl radical

CH3CH2•CuCl2CuSO4

CH3CH2• H2C=CH2 CH3CH2Cl

! Oxidation by CuSO4 is an electron transfer processes (outer-sphere)

Kochi, J. K. Science. 1967, 27, 415-424.

Oxidation of Alkyl Radicals by CuII

CH3CH2•+CuII CH3CH2+CuI +

Cu(OAc)2exclusive product

Cu(OAc)2

t-BuO Me

O

80% 20%

Me Cu(OAc)2 Me

20%

MeOAc

80%

CuII

55% 23% 22%thermodynamic distribution at 30 ºC: 2% 75% 20%

! Stabilities of the oxidation products do not control the selectivity of oxidative elimination

H2C=CH2 + H+

! Radicals which would give more stabilized carbocations give more substitution product

! Oxidation by CuCl2 is a ligand transfer processes (inner-sphere)

Kochi, J. K. Science. 1967, 27, 415-424.

Oxidation of Alkyl Radicals by CuII

CH3CH2•+CuII CH3CH2Cl

! Product ratios match those obtained with atom transfer reagents

CuICl Cl Cl

CuCl2Cl

Cu(OAc)2

! Oxidation of neopentyl radical gives no rearranged products with CuCl2

OAc

exclusive productcarbocation rearrangement products

ClCl

CuCl2:t-BuOCl:

70%70%

30%30%

! Analogy with Taube inorganic ligand transfer process

[CrII(H2O)5]2+

[CoIII(NH3)5Cl]2+[(H2O)5CrII–Cl–CoIII(NH3)5]4+

[CrIII(H2O)5Cl]2+

[CoII(NH3)5]2+

CuIICl ClH3CH2C

! Metal-alkyl bonds are characteristically weak, correlate with degree of steric crowding

Metal-Alkyl Bond Strengths

bond dissociation energy (kcal/mol)2

25201822241917

3741412121

53

SALOPH = N,N'-disalicylidene-o-phenylenediamine, (DH)2 = dimethylglyoxime

(py)(SALOPH)Co–CH2CH2CH3(py)(SALOPH)Co–CH(CH3)2(py)(SALOPH)Co–CH2C(CH3)3(py)(SALOPH)Co–CH2C6H5(PMe2Ph)(DH)2Co–CH(CH3)C6H5(PEtPh2)(DH)2Co–CH(CH3)C6H5(PPh3)(DH)2Co–CH(CH3)C6H5

(CO)5Mn–CH3(CO)5Mn–CF3(CO)5Mn–C6H5(CO)5Mn–CH2C6H5(CO)5Mn–COC6H5

(CO)5Re–CH3

Halpern, J. Inorg. Chim. Acta. 1985, 100, 41-48.Brown, D. L. S.; Connor, J. A.; Skinner, H. A. J. Organomet. Chem. 1974, 81, 403-409.

Connor, J. A. et al. Organometallics. 1982, 1, 1166-1174.



CH3CH2•H2C=CH2

CH3CH2X

CuII



L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

! Concerted pathway: cis insertion via a three-center, two-electron bond

Hegedus, L. S. Transition Metals in the Synthesis of Complex Molecules. 1999, 2nd ed.

Two-Electron Mechanisms of Oxidative Addition

! SN2-type substitution: highly nucleophilic metal complexes attack primary or secondary halides

L2Pd0

PhBr

L2PdBr

H

PhH

L2PdIIBr

Ph

IrICOPPh3Cl

Ph3PCH3Br

IrCOPPh3Cl

Ph3PCH3

+

Br– IrIII COPPh3Cl

Ph3PCH3

Br

! Radical pathway (two inner sphere one-electron processes)

Tsou, T. T.; Kochi, J. K. J. Am. Chem. Soc. 1979, 101, 6319-6332.

One-Electron Mechanisms of Oxidative Addition

IrI COPPh3Cl

Ph3PIn•

IrII COPPh3Cl

Ph3PIn

IrIIICOPPh3Cl

Ph3PInRX

X

R•

X

Mn

X

Mn+1 Mn+1X–

Mn+2+

X– Mn+2

X

! Electron-transfer mechanism (outer sphere one-electron process, then inner sphere one-electron process)

IrI COPPh3Cl

Ph3P R•IrII CO

PPh3ClPh3P

R

IrIIICOPPh3Cl

Ph3PRRX

X

R•

initiation:

propagation:

Labinger, J. A.; Osborn, J. A.; Coville, N. J. Inorg. Chem. 1980, 19, 3236-3243.

! Concerted pathway: requires retention of configuration

Stereochemical Consequence of Oxidative Addition Pathways

! SN2-type substitution: requires inversion of configuration

! Radical pathways: likely to proceed with loss of stereochemistry

Mn BrR1

R3

M Br

R1

R2 R3

‡

Mn+2R1

R2R3

+

Br– Mn+2R1

R2R3Br

MnBr

R1R2

R3

BrM

R1 R2

R3 Mn+2

Br

R1

R2R3

R2

Mn R1R2

R3

Mn+1

R1 R2

R3Mn+1

R1R2

R3

Br

R1R2

R3

Mn+2

R1 R2

R3Mn+2

R1R2

R3

Br

Br

‡

! Oxidative addition of alkyl halides to an IrI complex proceeds with loss of stereochemistry

Stereochemical Consequence of Oxidative Addition Pathways

IrICOPMe3Cl

Me3PIrI CO

PMe3ClMe3P

1:1 mixture

DPh

Br

FD

PhBr

F

Labinger, J. A.; Osborn, J. A. Inorg. Chem. 1980, 19, 3230-3236.

IrI COPMe3Cl

Me3P

Br

F

PhD

IrI COPMe3Cl

Me3P

Br

F

PhD

! Cross-coupling of endo- and exo-2-norbornane leads to the same exo product

González-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 5360-5361.

Br

Br

Ph

Ph

6% NiI26% trans-2-aminocyclohexanol

84%

91%NaHMDS (2 equiv.)isopropanol, 60 ºC

! Cis- and trans-1,2-dichloroethylene give the same isomeric mixture of oxidative addition product

Fitton, P.; McKeon, J. E. Chem. Commun. 1968, 4-6.

! Complete retention of configuration is observed in the oxidative addition to Pd(PPh3)4

Evidence for Radical Chain Process

Cl

Cl

Cl Cl

IrI COPMe3Cl

Me3P

IrIIICOPMe3Cl

Me3P

Cl

Cl

40:60 cis:trans

IrIIICOPMe3Cl

Me3P

Cl

Clor


Pd(PPh3)4

Cl

Cl

Pd(PPh3)4

Cl Cl

PdIIPPh3Cl

Ph3P

Cl

PdIIPPh3Cl

Ph3P

Cl

! Radical initiators promote the oxidative addition of alkyl halides to IrI complexes


! Radical inhibitors depress the oxidative addition of alkyl halides to IrI complexes


IrI COPMe3Cl

Me3PPh

Br

IrIIICOPMe3Cl

Me3P

Br

Phinitiator

5

noneAIBN

benzoyl peroxide

conversion (%)

after 100 min5

1134

after 46 h5

36100100

F

F

65 ºC

IrI COPR3Cl

R3P

PhBr

IrIIICOPR3Cl

R3P

Br

Ph inhibitor555

noneduroquinone

galvinoxyl

conversion (%)after 5 min

5

421419

F

FCO2Et EtO2C

r.t.

! Rate of reactivity of alkyl halides is consistent with radical process, inconsistent with SN2


! Trapping of radical intermediates with acrylonitrile


IrI COPMe3Cl

Me3PIrIIICO

PMe3ClMe3P

R

X

RX relative reactivity2

1.0 (defined)5.46.8

RX2

n-BuBrs-BuBrt-BuBr

CN

IrICOPMe3Cl

Me3PCN

n

IrIIICOPMe3Cl

Me3Pi-Pr

I

i-PrI

10 equiv.

CN

IrICOPMe3Cl

Me3PCN

n

IrIIICOPMe3Cl

Me3PMe

I

MeI

not observed

! Alkyl iodides bearing tethered alkenes undergo radical cyclization concomitant with oxidative addition

Phapale, V. B.; Buñuel, E.; García-Iglesias, M.; Cárdenas, D. J. Angew. Chem. Int. Ed. 2007, 46, 8790-8795.

Radical Cyclizations in Oxidative Addition

O O

I

BrZn O

O

OO

H

H

O

O

79%

[Ni(py)4Cl2] (10%)(S)-(s-Bu)-Pybox (10%)

THF, 23 ºC

O O O O

H

H

NiII

NiIII I

NiIO O

I

R

R =O

O

L*

NiI*L I

O O

CH2

O O

H

H

NiII

R

L*

O O

H

H

NiIII

R

L*I

! Isopropyl iodide accelerates the Kumada cross-coupling of aryl Grignard reagents

Manolikakes, G.; Knochel, P. Angew. Chem. Int. Ed. 2009, 48, 205-209.

Alkyl Iodide Accelerated Kumada Couplings

MgCl

Br OMe

rate enhancementdue to presence

of i-PrI

conversion after 15 min

8%82%

OMe

L Pd0 L PdI I

Ar1 Br

L PdII IBr

Ar1•

L PdIII IBr

Ar1L PdIII X

Ar2

Ar1

Ar2MgX

Ar1 Ar2 L PdI X

Me Me

! Rate acceleration arises from initiation of radical pathway by isopropyl iodide

PEPPSI (2 mol%)

THF, 0 ºC

Grignard prepared from PhCl and Mg/LiClGrignard prepared from PhI and i-PrMgCl•LiCl

I

MeMe

! Aryl halides bearing an alkene tether undergo radical cyclization

Manolikakes, G.; Knochel, P. Angew. Chem. Int. Ed. 2009, 48, 205-209.

Radical Cyclizations in the Accelerated Kumada Coupling

MgCl

OMe

Br

OMeOMe

additive

nonei-PrI (1.1 equiv.)

80%34%

7%50%

time

60 min5 min

MgCl

Br

OMe

OMe

78%

PEPPSI (2 mol%)

THF, 25 ºC

! No cyclized products are observed when the alkene tether is on the Grignard reagent

PEPPSI (2 mol%)

THF, 25 ºC, 5 minI

i-PrMgCl•LiCl

THF, -20 ºC, 1h



CH3CH2•H2C=CH2

CH3CH2X

CuII



L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

! Synthesis of !-lactones by reaction of Mn(OAc)3 with olefins

Oxidative Reactions with Manganese(III) Acetate

inner-sphereoxidation

MnIII OMnII

MnIII O

OCH2

Mn(OAc)3•2H2O (2 equiv.) O

O

PhHOAc, KOAc135 ºC, 1 h

proposed intermediate:

" "O

CH2HO

Heiba, E. I.; Dessau, R. M.; Koehl, W.J. J. Am. Chem. Soc. 1968, 90, 5905-5906.Heiba, E. I.; Dessau, R. M.; Rodewald, P. G. J. Am. Chem. Soc. 1974, 96, 7977-7981.

60%

MnIII OMnIII

OO

MnIII O

O

OO

Me

Me

Me MnIII OMnII

MnIII O

OR

! Key mechanistic question: Is the species that adds to the olefin a free or metal-complexed radical?

O

CH2HO

O

HO

styrene

Ph

outer-sphereoxidation

styrene

! No polymerization of styrene observed

Fristad, W. E.; Peterson, J. R.; Ernst, A. B.; Urbi, G. B. Tetrahedron. 1986, 42, 3429-3442.

Evidence Against Intermediacy of Discrete Radicals

no polymerization observed

O

OEtClH2Cno rxn OEt

O

Cl

C6H13C6H13

73%

(Ot-Bu)2

155 ºC

Mn(OAc)3•2H2O

HOAc, Ac2Oreflux

Mn(OAc)3•2H2O

HOAc, Ac2Oreflux

Bush, J. B., Jr.; Finkbeiner, H. J. J. Am. Chem. Soc. 1968, 90, 5903-5905.Allen, J. C.; Cadogan, J. I. G.; Hey, D. H. J. Chem. Soc. 1965, 1918-1932.

! Acetate esters add to olefins upon initiation with (Ot-Bu)2, but not Mn(OAc)3•2H2O

! No dimerization of acetic acid radicals observed

H3C OH

O Mn(OAc)3•2H2O

Ac2O, refluxno alkene

HO

OOH

O

succinic acid not observed

Bush, J. B., Jr.; Finkbeiner, H. J. J. Am. Chem. Soc. 1968, 90, 5903-5905.

! H/D exchange experiments show no rate dependence on the metal


Evidence for Metal-Complexed Radical

H3C

O

OH+

D3C

O

OD DH2C

O

OD

! !-lactone formation exceeds total solution H/D exchange

! Results are only consistent with rate-determining enolization of complexed acetate

rateA = rateB

KOAc, reflux

A: 0.25 M Mn(OAc)3•2H2OB: no metal

HOAc-d2

! Rate-determining enolization followed by single-electron oxidation generates metal-bound radical


Consensus Mechanism of Manganese(III) Acetate Oxidation

inner-sphereoxidation

MnIII OMnII

MnIII O

OCH2MnIII O

MnIIIO

O

MnIII O

O

OO

Me

Me

Me

MnIII OMnII

MnIII O

OPh

styrene

-H+

enolizationMnIII O

MnII

MnIII O

OCH2

oxidative lactonization

MnIII OMnII

MnIIO

O

Ph

! Mn(OAc)3 initiates radical cyclizations of !-keto esters and 1,3-diketones

Kates, S. A.; Dombroski, M. A.; Snider, B. B. J. Org. Chem. 1990, 55, 2427-2436.

Oxidative Cyclization of !-Dicarbonyls

O

OMe

O

Me

Mn(OAc)3•2H2O (2 equiv.)Cu(OAc)2•H2O (1 equiv.)

HOAc, 50 ºC, 1 h

O

OMe

OO

OMe

O

Cu(OAc)2

! Cu(OAc)2 is used to oxidize the alkyl radical to the alkene

O

OMe

O!-hydride

elimination O

OMe

O

Cu(OAc)

O

OMe

O

Me

71% (mixture of tautomers)

Me

OO

Mn(OAc)3•2H2O (2 equiv.)Cu(OAc)2•H2O (1 equiv.)

HOAc, 25 ºCO

O

Me

48%

O O

OMeMe

O O

OMeMe

Me

OCO2Me

Me

OCO2Me

Me

OCO2Me

(OAc)2CuMe

OCO2Me !-hydride

elimination

! Mn(OAc)3 can initiate radical cascade cyclizations

Zoretic, P. A.; Shen, Z.; Wang, M.; Riberio, A. A. Tetrahedron Lett. 1995, 36, 2925-2928.

Oxidative Radical Cascade Cyclizations

86%

(14% without Cu(OAc)2)

MnIIMn(OAc)3•2H2O (2 equiv.)Cu(OAc)2•H2O (1 equiv.)

HOAc, r.t., 26 h

OCO2Et

Me

MeMe

H

HO

43%

Me MeMn(OAc)3•2H2O (2 equiv.)Cu(OAc)2•H2O (1 equiv.)

HOAc, r.t., 24 hCO2EtH

Dombroski, M. A.; Kates, S. A.; Snider, B. B. J. Am. Chem. Soc. 1990, 112, 2759-2767.

! Baran's Cu(II)-mediated indole-carbonyl coupling

Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126, 7450-7451.Baran, P. S.; Richter, J. M.; Lin, D. W. Angew. Chem. Int. Ed. 2005, 44, 609-612.

Richter, J. M.; Whitefield, B. W.; Maimone, T. J.; Lin, D. W.; Castroviejo, M. P.; Baran, P. S. J. Am. Chem. Soc. 2007, 129, 12857-12869.

Indole Coupling via !-Carbonyl Radicals

O

NH

ONH

2 equiv.

ONH

43%

O

N

O

OMe

NH

Bn

54%, 5:1 d.r.

OH NH

Me

53%, single diastereomer(5 equiv. indole: 77%)

Me

Ph

O

Me

NH

30%

O

O Me

NH

51%

THF-78 ºC to r.t.

LHMDS (3.3 equiv.)Cu(II)2-ethylhexanoate (1.5 equiv.)

! Oxidation of enolate to !-ketoradical enables coupling with copper-coordinated indole


Proposed Mechanism of Indole-Carbonyl Coupling

O

NH

OCuII

N

OCuI

NOCuI

N

Cu0

O NH

THF-78 ºC to r.t.

LHMDS (3.3 equiv.)Cu(II)2-ethylhexanoate (1.5 equiv.)

! Free N-H is required for reactivity under copper conditions


Evidence for Electron Transfer via Copper Enolate

! Reaction proceeds with a known outer-sphere oxidant

no reaction

Fe+

discrete !-carbonyl radical

Me Me

N

SO O

O

N

Me Me

N

SO O

O

N

implicates inner-sphere oxidation via indole-bound copper enolate:

LHMDSCu(II)2-ethylhexanoate

-78 ºC to r.t.

PF6-

LHMDS, NEt3

Me Me

N

SO O

O

N

Me Me

N

SO O

O

N

11%, 4.5:1 d.r.(after benzoylation)

OCuI

NOCuII

N

! Enables the synthesis of 1,4-dicarbonyl compounds via !-carbonyl radicals

Oxidative Enolate Coupling

! Reaction does not proceed via formation of the !-bromoester

O

t-BuOOt-Bu

O

Rathke, M. W.; Lindert, A. J. J. Am. Chem. Soc. 1971, 93, 4605-4606.

t-BuO

OBr

t-BuO

OLi

t-BuO

O

Me

85%

O

t-BuOOt-Bu

O10%

! Proposed to proceed via single-electron oxidation of enolate to !-carbonyl radical

lithium amide baseCuBr2 (2 equiv.)

t-BuO

O

Me t-BuO

OCuII

t-BuO

OCuI

! Heterocoupling can be achieved in the coupling of imides or amides with ketones or esters

Oxidative Enolate Coupling

R1

O

R2 R3

R4

O

R1

O

R2 O

R4

R3

O

O N

O

PhBn

Me

O

Ph

Fe(III): 57%, 1.8:1 d.r.Cu(II): 55%, 1:1.6 d.r.

Fe(acac)3 (2.0 equiv.) orCu(2-ethylhexanoate)2 (2.0 equiv.)

LDA (2.1 equiv.)

THF, -78 ºC to r.t.

O

O N

O

PhBn

O

O

Fe(III): 60%, 2.6:1 d.r.

NMOM

O

1 equiv. 1 equiv.

Me

Me

OO

Fe(III): 73%, 2:1 d.r.

O

O N

O

CO2t-Bu

Phi-Pr

Cu(II): 62%, 1.2:1 d.r.(1.75 equiv. ester)

OBn

Baran, P. S.; DeMartino, M. P. Angew. Chem. Int. Ed. 2006, 45, 7083-7086.DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 11546-11560.

! Formation of ketone-iron enolate followed by single-electron oxidation furnishes !-carbonyl radical

Proposed Mechanism of Oxidative Enolate Coupling

O

O N

O

BnPh

MePh

O

O

O N

O

Bn

Ph

Ph

O

Li

LDAFe(III)

Me

FeIII

Ph

OMe

FeII

O

O N

O

Bn

Li

Ph

Me

O

Ph

O

O N

O

BnPh

Me

O

Ph

FeIII FeII

Baran, P. S.; DeMartino, M. P. Angew. Chem. Int. Ed. 2006, 45, 7083-7086.DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 11546-11560.

! Fe(III) and Cu(II) show divergent reactivity in cyclopropane radical clock studies

DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 11546-11560.

Mechanism of Oxidative Enolate Coupling

O

O N

O

Bn PhPh

MePh

OFe(III) or Cu(II)

LDA (2.1 equiv.)


O

O N

O

Bn

PhPh

Fe(III): traceCu(II): 20% (mixture

of ring-opened products)

O

O N

O

BnPh

Ph

O

Ph

Ph

Fe(III) or Cu(II)LDA (2.1 equiv.)


O

Ph

Ph Ph

Fe(III): traceCu(II): 14%

O

O N

O

Bn

MeMe Fe(III) or Cu(II)LDA (2.1 equiv.)


O

O N

O

Bn

MeMe

Fe(III): 27%Cu(II): 28%

! Fe(III) and Cu(II) promote cyclization with tethered olefins


Mechanism of Oxidative Enolate Coupling

! Extent to which metal enolate behaves like an !-carbonyl radical depends on the identity of the metal

X

O

Y

Mn

X

O

Y

Mn-1•R

•R

X

O

Y

R

X

O

Y

R




CH3CH2•H2C=CH2

CH3CH2X

CuII



L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

! Racemic starting material is converted to single enantiomer product via radical intermediate

Asymmetric Negishi Coupling of !-Bromoamides

O

Br

EtN

Bn

Ph

n-Hex ZnBr

O

n-Hex

EtN

Bn

Ph

90%, 95% eeracemic !-bromoamide

OEt

NBn

Ph

achiral radical intermediate

Fischer, C. F.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 4594-4595.

NiIO

EtN

Bn

Ph NiII

OEt

NBn

Ph NiIII

X

10% NiCl2•glyme13% (R)-(i-Pr)-Pybox

DMI/THF (7:1)0 ºC, 12 h

X

XX

OEt

NBn

Ph NiIII

Xn-Hex

n-Hex ZnBr

1.3 equiv.

NiII

NiIII Br

! Wide range of asymmetric cross couplings of racemic secondary alkyl halides has been developed

Asymmetric Cross Coupling of Alkyl Halides

Ph

O

Ph

Me

!-bromoketones

J. Am. Chem. Soc. 2005, 127, 10482-10483.

n-HexMe

89%, 96% ee81%, 92%

Angew. Chem. Int. Ed. 2009, 48, 154-156.J. Am. Chem. Soc. 2010, 132, 1264-1266.

Phn-Bu

Ph

84%, 94% ee

homobenzylic halides

J. Am. Chem. Soc. 2008, 130, 6694-6695.

secondary allylic chlorides

Me Me

n-Hex

95%, 87% ee

J. Am. Chem. Soc. 2008, 130, 2756-2757.

OMe

n-Hex

acylated halohydrins

N

OBn

Ph

80%, 94% ee

J. Am. Chem. Soc. 2010, 132, 11908-11909.

BHTO

OEt

Ph

!-bromoesters

80%, 99% ee

J. Am. Chem. Soc. 2008, 130, 3302-3303.

secondary benzylic halides

! A copper/chiral diamine catalyst controls the dimerization of 2-naphthol derivatives

Enantioselective Oxidative Biaryl Coupling

OH

CO2Me

N

N HCuIOMeO

O

N

N HCuIOMeO

O

OMe

OOH

H

OH

CO2Me

OH

CO2MeN

N HH

10 mol%

CuI (10 mol%), O2MeCN, 48 h, 40 ºC

enolization and catalyst release

HH

85%, 93% ee

N

N H

H

CuIIHO I

Li, X.; Yang, J.; Kozlowski, M. C. Org. Lett. 2001, 3, 1137-1140.Hewgley, J. B.; Stahl, S. S.; Kozlowski, M. C. J. Am. Chem. Soc. 2008, 130, 12232-12233.

! Iron(salan)-catalyzed process enables oxidative biaryl heterocoupling

Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu, T.; Katsuki, T. J. Am. Chem. Soc. 2010, 132, 13633-13635.

Enantioselective Oxidative Biaryl Coupling

(salan)FeIII

HO

FeIII(salan)OH

HO

O(salan)FeIII

O2

O2•–

O(salan)FeIV

+

O(salan)FeIII

HO+

HO

HOHO

X = H, Y = Br: 52%, 89% eeX = Ph, Y = CO2Me: 70%, 90%eeX = Ph, Y = Ac: 65%, 88%ee

X

X

X

X

Y

Y Y

HO

XO2

•–

H2O2



CH3CH2•H2C=CH2

CH3CH2X

CuII



L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

! Homolysis of cobalt-carbon bond generates carbon-centered radical capable of performing catalysis

Buckel, W.; Golding, B. T. Annu. Rev. Microbiol. 2006, 60, 27-49.

Coenzyme Vitamin B12 is a Source of Radicals

N N

NN

Me

Co

Me

H2NO

H

MeMe

H2N

O

H

H2N

OH

NH

O

OP

OOO

MeO

N

N

Me

Me

H

OHHH

Me

HOH

MeNH2

OH

NH2

O

O

NH2

H

MeMe

O

OH

OH

N

N

N

N

NH2

CoIII

CH2R

CoII

CH2R

BDE = 30 kcal/mol

5'-deoxyadenosyl radical

"latent radical reservoir"

! Glutamate mutase converts (S)-glutamate to (2S,3S)-3-methylaspartate

Buckel, W.; Golding, B. T. Annu. Rev. Microbiol. 2006, 60, 27-49.

Catalysis by Coenzyme Vitamin B12

CO2--O2C

NH4+

CO2-

-O2C

NH4+

CH2

CoIII

CH2

Ado

CoII

CH2

Ado

CH3

AdoCO2

--O2C

NH4+

CO2-

-O2C

NH4+

CH3

-O2C

NH3+

CO2-

glycyl radical

(S)-glutamate(2S,3S)-3-methylaspartate

! Methylmalonyl CoA mutase converts L-methylmalonyl CoA to succinyl CoA

Banerjee, R.; Ragsdale, S. W. Annu. Rev. Biochem. 2003, 72, 209-247.


CoIII

CH2

Ado

CoII

S

OCoA

O

O

HHH

S

OCoA

O

O

H H

O

OS

OCoA

O

OS

OCoA

succinyl CoAL-methylmalonyl CoA

CH2

Ado

CH3

Ado

O

O O

SCoA

! D-ornithine aminomutase converts D-ornithine to (2R,4S)-2,4-diaminopentanoic acid


CoIII

CH2

Ado

CoII

2,4-diaminopentanoic acidD-ornithine

CH2

Ado

CH3

Ado

CO2-

NH2

NCO2

-

NH2

Me

N

CO2-

NH2

N

R

CO2-

NH2N

R

R = pyridoxal phosphate

CO2-

NH2

H2C

N

R

R

R

Banerjee, R.; Ragsdale, S. W. Annu. Rev. Biochem. 2003, 72, 209-247.Chen, H.-P.; Wu, S.-H.; Lin, Y.-L.; Chen, C.-M. J. Biol. Chem. 2001, 276, 44744-44750.



CH3CH2•H2C=CH2

CH3CH2X

CuII



L PdII IBr

Ar1•

L PdIII IBr

Ar1 Ph

OMe

FeII

O

Br

EtN

Bn

Ph

O

n-Hex

EtN

Bn

PhCoII

CH2R

interaction of organic radicals with transition · pdf file!-carbonyl radicals metal-radical...

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