reaction mechanisms - harned research group · pdf fileof the more importatn reaction...

Reaction MechanismsBefore we get into the synthetic chemistry it is a good idea to first become familiar with someof the more importatn reaction mechanisms available to transition metals. We will see these

again and again as we continue in the course.

I. Ligand Substitution

II. Oxidative Addition/Reductive Elimination

M L1 L2+ M L2 L1+

M(n) + A Boxidative addition

reductive eliminationM(n+2)A

B

usually low-valent (n = 0,1),"nucleophilic" metal

coordinatively unsaturated

often polarized,"electrophilic"

M–A and M–B bonds areusually strong, complexcoordinatively saturated

metal has beenformally oxidized

Both associative (SN2-like) and dissociative (SN1-like) mechanisms are possible

M

Reaction Mechanisms

III. Migratory Insertion & Elimination

IV. Nucleophilic Attack on Ligands Coordinated to Metal

M Y M YX

X M Y XL L

note cisrelationship

note emptycoordination site

M X Y+ X Y Nuc–

M X Y Nuc

unreactive tonucleophiles

(electron-rich)

reactive tonucleophiles

(electron-deficient)

reactivity increasedif electron-deficeint

very reactive to other electrophiles,

often this process results in "reductive elimination" of the metal

Reaction Mechanisms

V. Transmetallation

M1 R M2 X+ M2 R M1 X+

M1 = Mg, Zn, Zr, B, Hg, Si, Sn, GeM2 = transition metal

almost always the rate-limiting step,usually the culpret when catalyticprocesses fail

VI. Electrophilic Attack on Metal Coordinated Ligands

Several different reaction modes are known, will explore further later

M R E+ M R R NucENuc–

inverstion at Rreductiveelimination

E R

retention at R

attack can directly cleave M–R bond orcan happen α, β, or γ to the metal

Ligand SubstitutionThough we will be concerning ourselves more with the reactivity and synthetic utility of organimetallic

complexes, understanding the mechanisms available for ligand substitution is critical to understanding how the complexes react.

Associative Mechansim (SN2-like) – typically occurs with coordinatively unsaturated complexes; exemplified by 16-electron, square planar, d8 metals (Ni(II), Pd(II), Pt(II), Rh (I), Ir (I))

M L1 L2+ M L2 L1+

MLT Lc

Lc X + Y

apicalattack

MLT Lc

Lc XY

MYX

Lc

Lc

LT MLT Lc

Lc Y

XM

LT Lc

Lc Y

X

– X

apicalexit

Factors that influence the rate:

– identity of the metal– identy of incoming and outgoing ligands– identy of the trans ligand ("trans effect")

squareplanar(16 e–)

squarepyramidal

(18 e–)

trigonalbipyramidal

(18 e–)

Ligand SubstitutionThough we will be concerning ourselves more with the reactivity and synthetic utility of organimetallic

complexes, understanding the mechanisms available for ligand substitution is critical to understanding how the complexes react.

Dissociative Mechansim (SN1-like) – typically occurs with 18 electron coordinatively saturated complexes; often slower that associative substitution; exemplified by M(0) metal carbonyl complexes

M L1 L2+ M L2 L1+

Ni(CO)4

(d10, 18 e–)

– CONi(CO)3

(d10, 16 e–)

+ LLNi(CO)3

(d10, 18 e–)

The rate can be accelerated by bulky ligands (loss of labile ligand relieves steric strain). This is particularly noticeable with phosphines and can be measured by the "cone angle". The

electronics of the phosphine can be changed (idenpendently from sterics) by substitution.

M

PR R

R

cone angle (Θ)

R θ

OMe 107OPh 128Ph 145

o-tolyl 194Cy 170

t-Bu 182

νco (cm-1)207920852069

–20562056

νco (cm-1) is determined with Ni(CO)3L and is a measurement of the amount of backbonding. More donating L, more backbonding and νco decreases.

Hartwig, Organotransition Metal Chemistry, 2010, pp 37–38.

M

Ligand SubstitutionA "full dissociation" is not always necessary to open coordination site on an 18-electron complex.

Sometimes a polydendate ligand can "slip" and free up a coordination site.

This can explain some observations seen with ligands such as η3-allyl, η5-cyclopentadienyl, and η6-arene complexes. By slipping to a lower hapticity, a coordination site (or two) is opened.

M M

η3-allyl(2 sites)

η1-allyl(2 sites) η6-arene

(3 sites)

Mη4-arene(2 sites)

Mη2-arene(1 site)

Mn(CO)3Mn(CO)3

Mn(I), d6

18 e–Mn(I), d6

16 e–

+ L

Mn(CO)3L

– CO

Mn(CO)2L

Oxidative Addition/Reductive EliminationReactions of this type are central to the synthetic utility of transition metals complexes and relies

on the ability of metals to easily and reversably change oxidation states (compare to what is takes to change oxidation state of C).



B

The terms "oxidative addition" and "reductive elimination" are generic and refer only to the process of changing the oxidation state of the metal. The exact mechanism by which this occurs can vary.

Oxidative Addition (OA)

Metal must be coordinatively unsaturated and relatively electron rich (nucleophilic) and usually in low oxidation state (0, +1). σ-Donor ligands (PR3, R–, and H–) facilitate OA. π-Acceptor ligands

(CO, CN–, alkenes) suppress OA.

By the formalism used to assign oxidation state, the metal has lost two electrons during the above process (the metal has been oxidized)

Metals that most commonly undergo OA reactions (other are certainly known):

d10: Ni(0), Pd(0) → d8: Ni(II), Pd(II)d8: Rh(I), Ir(I) → d6: Rh(III), Ir(III)

Exact mechanism by which the OA occurs depends on the nature of the substrate.

Oxidative Addition/Reductive Elimination

Nonpolar Electrophiles

Common examples: H2, R–H, Ar–H, R3Si–H, R3Sn–H, R2B–H, R3Sn–SnR3, R2B–BR2,

Generally undergo OA by concerted, one-step "insertion" mechanism. The configuration of any stereocenters would be expected to be retained. May require dissociation of a ligand from the

initial complex.

LnMA–B

LnMB

A

"agostic" interaction(2 e–, 3 center bond)

cis stereochemistry(kinetic)

Examples:

LnMA

BLnM

A

B

RCO

H

Ph3PIr

ClOC PPh3 H2

Ph3PIr

Cl

H PPh3H

COPh3P

RhCl

Ph3P PPh3

Ph3PRh

BR2

Ph3P PPh3H

Cl

R2BH

Ph3PRh

ClPh3P PPh3

Ph3PRh

Ph3P PPh3H

Cl

RCHO

O

R

Oxidative Addition/Reductive EliminationPolar Electrophiles

Common examples: HX, X2, R–X, R(O)X, Ar–X,

Two mechanisms are possible. One is analagous to reactions with nonpolar electrophiles (direct insertion). The other is an ionic, two-step SN2 mechanism, where the metal functions as a

nucleophile and donates two electrons in the process. The configuration of any stereocenters would be expected to be inverted in this case. The structure of the electrophile determines which is active.

Mn C X C XM CM(n+2) CMX X

relative rates:

Me > primary > secondary >> tertiary

I > Br ~ OTs > Cl >> F

phosphines promote with greater basicity giving faster rates

Oxidative Addition/Reductive EliminationPolar Electrophiles, cont'd

Examples:

OCIr

LL Cl

OCIr

L

L ClCH3

I

CH3I

trans(kinetic)

TsOt-Bu

D H

H DL2Pd

t-BuH D

H DTsO

Pd(0)Pt-Bu2Me

L2Pd PhBr+

inversion

L2PdBr

PhHtrans

PhL2Pd

Br

trans(retention)

Fe(CO)5

d8, 18 e–

PhPhONa

Na2[Fe(CO)4]2–

Collman's reagent"supernucleophile"

R XNa[RFe(CO)4]–

Further reactions possible

Oxidative Addition/Reductive EliminationPolar Electrophiles, cont'd

There are also examples of reactions that cannot be explained by either of these mechanisms (concerted or SN2). These have been rationalized by a radical-chain mechanism.

R Xhν or

O2RR

R + LnMn R M(n+1)Ln

R M(n+1)Ln RX+ R M(n+2)Ln

XR+

sequential 1e– oxidations,net 2e– oxidation of metal

Oxidative Addition/Reductive Elimination



BReductive Elimination (RE)

The reverse of oxidative addition. Concerted mechanism proceeds with retention of any stereochemical information. Nucleophilic attack on the ligand would invert the configuration.

Factors that influence:– First row metals faster than second row, faster than third row– Electron-poor complexes react faster than electron-rich– Sterically hindered complexes reacter faster– H reacts faster than R– complexes with 1 or 3 L-type ligands faster than 2 or 4

Geometry of the complex is also quite important

PPd

P Me

Me

Ph Ph

Ph Ph

fastMe Me PPh2Ph2P Pd

Me

MeΔ

no reaction

Migratory Insertion & Eliminations

Migratory Insertion

M Y M YX

X M Y XL L

In this process an unsaturated ligand (CO, RNC, alkene, alkyne) inserts into an existing M-ligand bond. The two ligands involved must be cis to one another. These are usually reversible processes. At the end

of the reaction the metal is left with an empty coordination site.

General examples:

LnMR

CO

LnML

C

R = aryl, alkyl, H

+ L

OR

LnMR LnM

L+ L

A B A H B

RH

trans trans

LnMR

LnML+ L

B

A

R

BA

cis


β-Hydride Elimination (BHE)

If an alkyl metal complex has hydrogens b to the metal, then this type of elimination is likely to occur. However, the β-hydrogens usually must be syn coplanar to the metal. Also the metal

usually must have an open coordination site.

Eliminations are the reverse reaction of migratory insertion and can occur one after the other. The group being eliminated does not have to be the one that participated in the insertion.

There are several types of eliminations.

HLnM

syn coplanar

LnM HLnM H

BHE from transition metal-alkoxides and -amines are also important

OHLnM

MeMe

LnM H

OMeMe LnM H

L+ L

Me

O

Me+

M–H without using H2

β-Eliminations of alkoxides and halides are known.


α-Hydride Elimination (AHE)Elimination of an α-hydrogen from metal alkyl complexes. This forms a carbene. Much slower than β-elimination processes and usually only occur when BHE is not possible. More common

with early transition metals (d0, group 4 and 6), but can happen with later metals.

Eliminations are the reverse reaction of migratory insertion and can occur one after the other. The group being eliminated does not have to be the one that participated in the insertion.

There are several types of eliminations.

LnMH

HLnM

HH

Often induced by ligand exchange processes.

V

Cp

Me3P

t-Bu

t-Bu

PMe2Me2P+ V

Cp

PP

MeMe

MeMe

t-Bu + tBuCH3 + PMe3

MM

Nucleophilic Attack on Coordinated Ligands

Attack on Metal-Bound Carbonyl – The nucleophile is typically strong nucleophiles, like RLi

Many different kinds of examples of this. From our prespective the more important ones involve attack on M–CO complexes and M–alkene/alkyne complexes.

LnM C O

Ln is good π-acceptor(another CO)

RLi

LnM R

O

acyl "ate" complex

usually quite stable and can be further manipulated

Attack on M–C σ-Bonds – Such bonds are often intermediates in catalytic reactions. The carbon can be sp2 or sp3 hybridized. Nucleophilc reactions with η3-allyl complexes fall in this category. Can also be considered as a "reductive elimination" process.

ArPd

O

L

LX ROH

PdLn ArCO2R+ + HX

Nuc–Nuc

Nucleophilic Attack on Coordinated Ligands

Many different kinds of examples of this. From our prespective the more important ones involve attack on M–CO complexes and M–alkene/alkyne complexes.

Attack on M–C π-Bonds – By ligating the metal, alkenes and alkynes usually become electrophilic. This makes then susceptible to nucelophilic attack. Depending on how the nucleophile reacts, the addition can be syn or anti.

M

Nuc–

M

Nuc"external" addition of nucleophileproduct of anti addition(most common pathway)

M Nuc

insertion

M

"internal" addition of nucleophileproduct of syn addition

Nuc

Other nucleophilic reactions will be covered as needed

Nuc–

Transmetallation

M1 R M2 X+ M2 R M1 X+

M1 = Mg, Zn, Zr, B, Hg, Si, Sn, GeM2 = transition metal

Importance is growing as this is a key step in useful methods for constructing C–C bonds, particularly such bonds that are difficult to forge by other means. However, the exact mechanism by which

transmetallation occurs is not well understood and seems to be quite dependent on the metal species.

Generally speaking, transmetallation involves replacing the halide or pseudohalide in a transition metal (M2) complex with the organic group of a "main group" organometallic (M1) reagent. This step is almost always the rate-limiting step and is usually the culpret when cross-coupling reactions fail.

This is an equilibrium, so to ensure success both partners must gain some thermodynamic benefit. Often this can be enhanced by appropriate "activation" of the main group element.

Isomeric integrity (cis, trans) is usually maintained when R is an olefin. With alkyl metals the situation is more complicated. With polar solvents, alkylstannanes can transmetallate with inversion of

configuration (open transition state?), but in less polar solvents retention is seen (closed transition state?). However, aliphatic organoboron reagents tend to proeed with retention.

Pd

R

XL

LC SnBu3

proposed open t.s.leading to inversion

Pd

R

XL

LC

SnBu3

proposed open t.s.leading to retention

similar mechanisms could be drawn with other metals under apprpriate

activation

Fe

Electrophilic Attack on Coordinated LigandsSeveral different reactivity modes depending on the metal, ligand, and electrophile involved. More

specific examples will be discussed as needed.

Electrophilic cleavage of σ-alkyl metal bonds – Note metal is removed.

R M + E+ R E + M+ retention at R

Me Fe(CO)2Cp Me DDCl CpFe(CO)2Cl+

Attack at α-position – Forms carbenes

M CHPhH

+ M CH

PhM C R + M C

H

Ph

H+Ph3C+

OCOC CH2OH

Fe

OCOC CH2

TMSOTf

CH2Cl2–90 ºC

TfO–

+ Me3SiOH



Attack at β-position

+ + E+Ph3C+H

M M M ME

M R + E+ M CE

R

vinylidene

Mn

OCOC

Mn

OCOC C

MeOTf

CO2Me

Me

CO2Me

(OC)5W Ph

O

(OC)5W Ph

O Me3OBF4(OC)5W

Ph

OMe



Attack at γ-position

+ E+M ME

+M MA

A

BB

MA

B

SnBu3

R2

R1 + R3CHO PdCl2(PPh3)2

R3

OH

R1

R2

likely involves formation of η1-allyl intermediate

Cp(CO)3Mo

Me

ArSO2NCO+N

Me

Cp(CO)3Mo

O

SO2Ar

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