M.C.

White, Chem 153 Mechanism -1- Week of September 18th, 2012

Elementary organometallic reactions can

Reaction Mechanisms usually be classified as one of the following:

e- count ox. state

1. A mechanism is a theory deduced
from the available experimental data. ligand dissociation
-2 0
The experimental results are the MLn MLn-1 + L
ligand association
facts; the mechanism is conjecture
based upon these facts.

X reductive elimination
LnM + X Y -2 2
2. A mechanism the simplest LnM
Y oxidative addition
rationalization that is consistent with all
of the available data.
bond metathesis LnM R
MLn R
0 0
X M' 4-centered reaction X M'
3. A mechanism should provide
experimentally testable
predictions and can only be L insertion
disproved, never proven. LnM LnM L R -2 0
R de-insertion

Lewis acid
activation of
electrophile
LnM E + Nu LnM E Nu 0 0
M.C. White, Chem 153 Mechanism -2- Week of September 18th, 2012

Organometallic Reaction Mechanisms

1. Ligand Association/Dissociation

ligand dissociation
MLn MLn-1 + L
ligand association

Example:

Pd(PPh3)4 Pd(PPh3)3 + PPh3 Pd(PPh3)2 + PPh3

18 e- 16 e- 14 e-

Topics Discussed

1.Associative

2.Dissociative
M.C. White, Chem 153 Mechanism -3- Week of September 18th, 2012

Ligand Exchange Mechanisms

Associative ligand substition: is often called square planar substition because16 e-, d8 square planar complexes generally undergo ligand
substitution via an associative mechanism (the M-Nu bond is formed before the M-X bond breaks). The intermediate is 18e- and therefore
provides a lower energy route to the product than a 14e- intermediate formed via dissociative substitution (the M-X bond is fully broken
before the M-Nu bond begins to form). Analogous in many ways to SN 2 reactions.

Nu empty, non-bonding pz orbital can act as an

acceptor orbital for the e- density of the
incoming nucleophile

Nu L

L L L L Nu L L L L
M M L M M M
L X L X L Nu L Nu
X
L X
16 e- 18 e- intermediates 16 e-

M = Ni(II), Pd(II),
Pt(II), Rh(I), Ir(I).

Dissociative ligand substitution is

most favored in coordinatively saturated
L L L
18e- complexes (e.g. d10 tetrahedral, d6 -
X
octahedral). In the dissociative L L L L L L
Nu:
mechanism, the M-X bond is fully M M M
broken before the M-Nu bond forms
L X L L Nu
thereby avoiding an energetically
unfavorable 20e- intermediate. L L L
Analogous in many ways to SN1
reactions. 18e- 16e- 18e-
Note that in all ligand substition M = Ru(II), Co(III),
processes, there is no oxidation Rh(III), Ir(III)
state change at the metal center.
M.C. White, Chem 153 Mechanism -4- Week of September 18th, 2012

MO Description of bonding in ML4 square planar

L
L M L
Metal ValenceOrbitals L Linear Combinations of
Ligand Donor Orbitals
a2u
16 e - Rule:
pz
The square planar geometry is favored by d8
metals (e.g. Ni (II), Pd (II), Pt(II), Ir (I), Rh(I)).
a2u a2u
eu eu A stable electronic configuration is achieved at
px py LUMO 16 e-, where all bonding and non- bonding
* orbitals are filled. Spin-paired compounds
display diamagnetic behavoir (i.e. weakly
a1g a1g
repelled by magnetic fields) and may be
When combining orbitals, the resulting
s MO's must be symmetrically dispersed readily characterized by NMR.
between bonding and antibonding.
y Thus, combining 3 orbitals (i.e. a1g's)
requires one of the orbitals to be non- L
a1g L L
x bonding. n L
dz 2 a1g HOMO
b1g
eg eg
b2g b2g
b1g n

dx 2-y2
b1g

eg In a square planar ligand field the

degenerate d orbitals split into eu
orbitals of a1g, b 1g, eg, and b2g
dxz dyz
symmetries. The degenerate p

orbitals split into orbitals of eu and a1g
b2g a2u symmetries.

dxy
M.C. White, Chem 153 Mechanism -5- Week of September 18th, 2012

Associative Substitution:the nucleophile

Nu

Rate = -d [PtCl2] = k 1[PtCl2 ] + k 2[Nu][PtCl2 ]

dt Cl N Cl N
PtII MeOH, rt PtII
k1 : first order rate constant that arises from + Cl-
N Cl N Nu
substition of leaving group by solvent.
k2 : second-order rate constant for bi-molecular 16 e- 16 e-
attack of Nu on metal complex.

Nu relative rate Nu relative rate

MeOH 1 1549
CH3CO2- <100
CO <100 N
Basicity of the incoming ligand
F- <158 N
(nucleophile) plays only a minor
2754
role in its reactivity for soft
metal centers. In general, the 158 N
H
softest (i.e. most polarizable) N
nucleophiles react fastest with
soft metals like Pt(II) via CH3O- <250 Br- 15,000
associative substitution. Steric (Et)3N 1175 I- 2.9 x 105
hinderance at the nucleophile C6H11CN 2.2 x 106
(i.e. picoline vs pyridine) can (CH3O)3P 1.7 x 107
retard the rate of substition. 1349
PhS- 1.5 x 107
N Ph3P 8.5 x 108
H
Et3P 9.8 x 108
Cl- 1096
NH3 1175
M.C. White, Chem 153 Mechanism -6- Week of September 18th, 2012

Associative Substitution: Sterics

Sterically shielding the positions above and below the plane of the square planar complex can lead to
significant decreases in the rates of associative substition.

Et3P Et3P
PtII N , rt PtII + Cl
-
Et3P Cl Et3P Py
k2 =
100,000 M-1 sec-1

, rt
Et3P
PtII
N Et3P
PtII + Cl-
Et3P Cl k2 = Et3P Py
200 M -1 sec-1

Et3P N , rt Et3P
PtII PtII + Cl-
Et3P Cl k2 = Et3P Py
1 M -1 sec-1

Pearson J. Chem. Soc. 1961 2207.

M.C. White, Chem 153 Mechanism -7- Week of September 18th, 2012

Associative Substitution: Sterics

as the steric bulk of the imine backbone increases, the
aryl groups become more rigidly locked perpendicular
to the square plane making their ortho substituents
more effective at blocking the axial sites above and
below the plane.
associative second order rate constants for
ethylene exchange were examined by 1HNMR
in CDCl2 at -85o C
+ +

+ (BAr'4) - (BAr'4) -

N N N
(BAr'4) -
Pd Pd Pd
N CH3 N CH3 N CH3

k = too fast to measure k = 8100 L/mol/sec k = 45 L/mol/sec

even at -100o C. Brookhart JACS 1995 (117) 6414.

(BAr'4 )-
N CH3 R
= Pt
N
M.C. White, Chem 153 Mechanism -8- Week of September 18th, 2012

Brookhart Polymerization Catalysts

+ +

(BAr'4) (BAr'4)
- -
N N
Pd Pd
CH3 N CH3
N

Polymer Mw = 110,000 Polymer Mw = 390,000

+ + +
R - R (BAr'4 )-
R (BAr'4 )-
(BAr'4 )
N N CH3 N CH3
Pd High Mw
Pd Pd
CH3 insertion polymer N
polymers
N N
H propagation
R R R

-hydride
elimination

+ + + +
R (BAr'4 )- R (BAr'4 )- R R
(BAr'4 )- (BAr'4 )-
associative
N N displacement N N
Pd CH3 Pd CH3 Pd
Pd
N H N H N H N H
R R R R
Low Mw
polymers

Brookhart JACS 1995 (117) 6414.

 M.C. White, Chem 153 Mechanism -9- Week of September 18th, 2012

Ligand Exchange: Dissociative Mechanism

The rate-determining step in a dissociative
ligand substition pathway is breaking the M-L
bond. Because of the late, product-like
transition state for forming the coordinatively
O unsaturated intermediate in such a process, the
RhI RhI
14 M-L BDE is a good approximation of the
10 slower
O activation energy(EA ).
at 25oC
16 e- 18 e-

rate of ethylene exchange via rate of ethylene exchange via RhI

associative displacement at dissociative displacement at

E
25oC is ~ 10 4 sec -1 25oC is ~ 4 x 10 -10 sec-1 EA BDE
RhI
BDE = 31 kcal/mol

rxn coordinate

PPh3 (mmol) k x 104 sec -1

0.20 1.65

PPh3 RhI PPh3

RhI RhI 1.23 1.73
118oC
a 6-fold increase in the
concentration of nucleophile does
not significantly affect the rxn
18 e- 16 e- 18 e-
rate. Results are consistent with a
mechanism where the rate-
determining step is ethylene
rate = -d [LRh(C2 H4 )2] = k1 [LRh(C2H4 )2] dissociation and is not affected by
the concentration of the
Cramer JACS 1972 (94) 5681. dt
nucleophile.
M.C. White, Chem 153 Mechanism -10- Week of September 18th, 2012

Ligand dissociation: sterics

t-Bu
P t-Bu
P t-Bu t-Bu
P Fe
Fe Pd0 P
P Fe Pd0 Fe
P catalyst "resting state"
P
P t-Bu t-Bu

t-But-Bu
"ineffective catalyst"

+L dissociative -L
The steric bulk of the bidentate phosphine
ligand is thought to weaken the Pd-P bond, t-Bu
t-Bu
thereby favoring ligand dissociation required P
to form the catalytically active species.
catalytically active
Fe Pd0
species
P
t-Bu
t-Bu
Cl + H2N N
NaOt-Bu H

also aryl Br, I, OTs also aniline, piperidine

Hartwig JACS 1998 (120) 7369.

M.C. White, Chem 153 Mechanism -11- Week of September 18th, 2012

Ligand dissociation: or hv
coordinatively and
electronically unsaturated
complexes capable of
oxidatively adding into
unactivated C-H bonds.

hv or
RhI CO RhI RhIII H

OC CO OC OC
18 e- 16 e- 18 e-

Light-promoted ligand dissociation

M-CO M-CO H
RhI
OC
hv
proposed
intermediate

bond order = 1 bond order = 0

Bergman JACS 1994 (116) 9585.

M.C. White, Chem 153 Mechanism -12- Week of September 18th, 2012

Ligand dissociation:weakly coordinating solvents

First generation Crabtree hydrogenation catalyst +

P(Me)Ph2
Ir (PF 6- )

P(Me)Ph2
cat.

R H2, solvent (S) R

A glimpse into the catalytic cycle

+ (PF 6- ) H + (PF 6- ) H + (PF 6- )

H
dissociative
Ph 2(Me)P H displacement Ph 2(Me)P H Ph 2(Me)P H
IrIII R IrIII
IrIII
S P(Me)Ph2 S P(Me)Ph2 S P(Me)Ph2
S
S
catalytically active species R

Solvent (S) Turnover Frequency (TOF)

O
~10 0 0

CH2Cl2 5100 3800 1900

TOF = mol reduced substrate/mol catalyst/h Crabtree Acc Chem Res 1979 (12) 331.
M.C. White, Chem 153 Mechanism -13- Week of September 18th, 2012

Organometallic Reaction Mechanisms

2. Oxidative Addition / Reductive Elimination

X reductive elimination
LnM LnM + X Y
Y oxidative addition

Me
*Cp(Me3P)Ir Ir(PMe3)Cp* *Cp(Me3P)Ir
-C6H12 H
H
Ir(III), 18 e- Ir(I), 16 e- Ir(III), 18 e-

Topics Discussed

1.OA mechanism and trends

2.RE mechanism and trends

3.Mechanistic probes
M.C. White, Chem 153 Mechanism -14- Week of September 18th, 2012

Oxidative Addition/Reductive Elimination

Oxidative Addition (OA): metal mediated breaking of a substrate -bond and formation of 1or 2 new M-L bonds. OA requires removal of 2
electrons from the metal's d electron count. This is reflected in a two unit increase in the metal's oxidation state. The formation of 1 or 2 new
M-L bonds is accompanied by an increase in the metal's coordination number by 1 or 2 units respectively. The latter results in a 2 unit
increase in the electron count of the metal complex (e.g.16 e - to 18 e-). Currently, OA of low valent, electron rich metals to polar substrates is
the best way to form M-C bonds within the context of a catalytic cycle. The term oxidative addition confers no information about the
mechanism of the reaction.

R +
oxidative addition
LMn + R X L M (n+2) or L M(n+2) R X-
"Nu:" "E+" reductive elimination X

Reductive elimination (RE): microscopic reverse of oxidative addition where two M-L bonds are broken to form one substrate bond. RE
results in the addition of two electrons into the metal d electron count. This is reflected in a two unit decrease in the metal's oxidation state. The
breaking of 2 M-L bonds is accompanied by a decrease in the metal's coordination number by 2 units. The result is a 2 unit decrease in the
electron count of the metal complex (e.g. 18e- to 16 e-). The two M-L bonds undergoing reductive elimination must be oriented cis to each
other. Currently, RE is the most common way to form C-C bonds via transition metal complexes.
General OA Mechanisms:
Concerted (generally for non-polar substrates) Nucleophilic displacement (generally for polar substrates)

A A
A A + -
n (n+2) +
LxM + LxM n LxM LxM n
LxMn A X LxM(n+2) A
+ + X-
B B X
B
3-centered TS cis addition

Radical (both non-polar and polar)

A
A
LxMn + LxM(n+1) A C LxM(n+2)
C
C
M.C. White, Chem 153 Mechanism -15- Week of September 18th, 2012

Oxidative Addition
Metal Complex: electron rich metals in low oxidation states, with strong donor ligands and a site of coordinative unsaturation.

d10, tetrahedral, 18 e- --> d10, ML2, 14e - --> d8 , ML4, square planar, 16e - (e.g. Ni0 , Pd0 , Pt0)

t-Bu t-Bu t-Bu

t-Bu t-Bu t-Bu
P t-Bu t-Bu P P
Cl Cl
P
Fe Pd 0 Fe Fe Pd 0 Fe Pd
P
P t-Bu t-Bu P OA P
L t-Bu
t-Bu
t-Bu t-Bu t-But-Bu

d8, ML4 , square planar, 16 e- --> d6 , ML6, octahedral, 18e- (e.g. RhI, IrI)
H
+
H
P(Cy)3
IrI (PF 6- ) IrIII
H2
P(Cy)3
N
N
16e-

18 e-
Substrates: two groups segregated into non-polar and polar. Currently, the most facile way to form C-M bonds is with polar substrates
(e.g. alkyl, aryl, and vinyl halides).
Non-polar substrates: R-H Polar substrates: R-X where X = I, Br, Cl, OTf

H O X O
H2, R3Si-H, R2 B-H, RCH2-H, R H , , , R H-X, RCH2-X, , , R
H X
H X
M.C. White, Chem 153 Mechanism -16- Week of September 18th, 2012

OA: Concerted 3-centered (non-polar substrates)

H
H -backbonding>>
-donation
M M
oxidative addition
H
H

-complex metal dihydride

-complex: intermolecular binding of a substrate via it's -bond to a metal complex. -complexes are
thought to be along the pathway for oxidative addition of non-polar substrates to low valent, e-rich metal
complexes. Analogous to the Dewar-Chatt-Duncanson model for olefin metal-bonding, -bonding is thought
to occur via a 2 way donor-acceptor mechanism that involves -donation from the bonding -electrons of the
substrate to empty -orbital of the metal and -backbonding from the metal to the * orbitals of the
substrate. These bonding principles have been applied to non-polar -bonds such as H-H, C-H, Si-H, B-H
and even C-C bonds.

H H
H H
LxM n + LxM n LxM n LxM (n+2) >1.6
H H H
0.74 0.84 H

-complex -backbonding>> metal

-donation dihydride

Concerted mechanism: -complex formation precedes an early (little -bond breaking), 3-centered
transition state where strong -backbonding results in oxidative addition of the bound substrate to the metal.
The concerted mechanism is thought to operate primarily for non-polar substrates (i.e. H-H,C-H, Si-H, B-H)
with electron rich, low valent metals. The spectroscopic identification of metal dihydrogen -complexes with
H-H bond distances stretched between the non-bonding (0.74 ) and dihydride extremes (>1.6) provides
strong support for this mechanism with H2.
M.C. White, Chem 153 Mechanism -17- Week of September 18th, 2012

sp3C-H OA via complex intermediates

H
H -backbonding>>
-donation
M M Hydrido(alkyl)metal
oxidative addition complex
C

C
-complex

regioselectivity: sp 2 C-H > 1o sp3C-H> 2o sp3 C-H >>> 3o sp3 C-H. There is both a kinetic and thermodynamic preference to
form the least sterically hindered C-M bond. Kinetic preference: activation barrier to -complex formation is lower for less
sterically hindered C-H bonds and bonds with more s character. Thermodynamic preference: stronger C-M bonds are formed
(see Structure and Bonding, pg. 32).
Evidence in support of a -complex intermediate:

CD3
D3C CD3
CD3
D
hv (flash), Kr (165K) RhIII D
RhI CO RhI [Kr] RhI
D2C CD2
OC
OC CO OC OC
CD3 D3C
CO v (1946 cm -1) CD3
18 e- D3C CD3 CD3

CO v (1947 cm -1) CO v (2008 cm -1)

-complex

Bergman JACS 1994 (116) 9585.

M.C. White, Chem 153 Mechanism -18- Week of September 18th, 2012

sp3C-H: concerted vs. radical

crossover experiment: evidence in support of a concerted mechanism.

H
IrI IrIII H
H3C OC OC

D12

hv
IrI CO IrI

OC CO OC
D
18 e-
IrI IrIII D

OC OC

D11 D11
-complexes

Less than 7% of the crossover products were observed by 1 HNMR. This may be indicative of a minor radical pathway.

H2C

D11
IrII H + IrII D IrIII H IrIII D

OC OC OC OC

Bergman JACS 1983 (105) 3929. D11

M.C. White, Chem 153 Mechanism -19- Week of September 18th, 2012

Agostic interactions: intramolecular -complex

H
R An agostic interaction is generally
defined as an intramolecular
M C -complex that forms between a
metal and a C-H bond on one of its
R ligands.

Brookhart JOMC 1983 (250) 395

CO
H PPh3
RuII
Ph3P PPh3
H
5 mol%
O Y OEt
OEt
-CO
O OEt Y O O
O O O O
O
PPh3
H Ru0(PPh 3)3 0 PPh3
H Ru OA
RuII
O O Toluene, reflux O O PPh3 H
O O PPh3
O O PPh3 PPh3
O
Si(OEt)3

The strategy of identifying substrates that can act as O

transient metal ligands has led to the only synthetically
useful examples of C-H-> C-M (C-H activation) to O OEt
O
date. Like all substrate directed reactions, the scope of
such processes is limited. Si(OEt)3
Trost JACS 1995 (117) 5371 O O
O
M.C. White, Chem 153 Mechanism -20- Week of September 18th, 2012

OA: sp3C-sp3C
C

CR3 -backbonding>>
-donation
M M
oxidative addition
C
R
R R C

-complex metal dialkyl complex

Even though BDE's of C-C bonds are lower than those of analogous C-H bonds (e.g. C6H5-CH3:100 kcal/mol vs.
C6H5-H: 110 kcal/mol), transition metal mediated OA's into C-C bonds are much more rare than those for
analogous C-H bonds. Formation of the -complex is kinetically disfavored by steric repulsion between the metal
complex and the carbon substituents and by the high directionality of the sp3C-sp3C bond that localizes the
bonding orbital deep between the carbon nuclei. Milstein and coworkers are able to overcome the kinetic barrier
by approximating the C-C bond at the metal center.

Pt-Bu Pt-Bu Pt-Bu

[(C2H4 )2RhCl]2 -50oC

RhI Cl RhIII Cl
-4
-80oC, tol k = 2 x 10 /sec

NEt2 NEt2 NEt2

stable @ -80o C only product observed

observed by 1H NMR (no C-H activation product)

Milstein JACS 2000 (122) 9848.

M.C. White, Chem 153 Mechanism -21- Week of September 18th, 2012
OA with Csp2-X bonds: aryl and vinyl halides

LxM n + oxidative addition

X LxM (n+2)
X

R
R
LxM n + X oxidative addition LxM (n+2)
X

Note: retention of stereochemistry in OA to vinyl halides

Rate of OA X = I>Br>Cl>>F

Three main mechanisms to consider for this process:

1. Concerted process with unsymmetrical, 2. SNAr-like with highly charged 3. Single-electron transfer processes with
minimally-charged, 3-centered transition state transition state oppositely-charged, radical intermediates

LxM (n+1)( )
Csp2 LxM n
LxM n
X
X X
M.C. White, Chem 153 Mechanism -22- Week of September 18th, 2012
OA: Csp3-X:alkyl, allyl, and benzyl halides

Nucleophilic displacement (generally for polar substrates)

A + -
+
LxM n + LxM n A X LxM (n+2) A + X-
X

" Stereochemistry is the single most valuable type of mechanistic evidence in reactions that make or
break bonds to tetrahedral carbon." G.M. Whitesides (JACS 1974 (96) 2814).
+
CO2Me CO2Me CO2Me
(PPh3)4Pd
5 mol% (OAc-)
inversion
MeO 2C
+
CO2Me
OAc Na
(Ph3P) 2PdII
MeO 2C CO2Me
MeO 2C
inversion
net retention
Trost Acc. Chem. Res. 1980 (13) 385.
MeO 2C

Mes +
P (OTf- )
Pd II +
Mes Ph (OTf- )
P P
2 mol%
Mes
Ph Pd II + Ph
H2N
P
OH NH2 NHPh
Mes

Ozawa JACS 2002 (124) 10968.

M.C. White, Chem 153 Mechanism -23- Week of September 18th, 2012
Reductive Elimination

Reductive elimination is a key transformation in transition metal mediated catalysis, often representing the product
forming step in a catalytic cycle.
General trend for reductive elimination from d 8 square planar complexes:

H H H H C(sp3)
M > M > M > M > M
2 3
H C(sp) C(sp ) C(sp ) C(sp3)

Orbitals with more s character are less directional and lead to better overlap in the transition
state for reductive elimination (RE). Note: cis orientation of the ligands is required for RE
to occur.
Best overlap Worst overlap

1.51 1.55 1.52 1.55 CH3

H H H H CH3 2.25
1.96

Pd 73o 1.73 Pd 51o 1.33

80o 2.39 Pd 51o 1.57
Pd Pd 56o 2.11
92o 2.82
Pd
H H
1.95 1.99 CH3
CH3 CH3
metal dihydride Transition state (TS)
1.96
Calculated E = 1.55 kcal/mol CH3
Transition state (TS)
hydrido(alkyl)metal Transition state (TS) Calculated E = 22.6 kcal/mol
Pd-H bond is stretched complex Calculated E = 10.4 kcal/mol
only 2% in TS metal dimethyl Pd-H bond is stretched
~10% in TS

Computational studies suggest that

the spherical symmetry of the s
Goddard JACS 1984 (106) 8321. orbitals of H allows the simultaneous
Dedieu Chem. Rev. 2000 543. breaking of the M-L bonds while
making the new bond of the product.
M.C. White, Chem 153 Mechanism -24- Week of September 18th, 2012
RE: Bite Angle Effects

RE can be promoted by:

Increasing the bite angle of the ligand

Increasing electrophilicity of metal center e.g.
( -acids)
Ligand dissociation

TMS

P CH2TMS P CH2TMS
P
C
Pd II 80oC Pd II Pd II
N
P CN k P C P
N

Ph 2 Ph 2
Ph 2 P P
O
P CH2TMS CH2TMS CH2TMS
Pd II Pd II Pd II
CN
P CN P CN O P
bite angle Ph 2 Ph 2 Ph 2

bite angle: 85o bite angle: 90o bite angle: 100o

k = 2.1 x 10-6 k = 5.0 x 10-5 k = 1.0 x 10-2

Large bite angles of diphosphines have been shown to enhance the rates of reductive elimination from
square planar complexes presumably by bringing the two departing ligands closer together.

Moloy JACS 1998 (120) 8527.

M.C. White, Chem 153 Mechanism -25- Week of September 18th, 2012
RE: -Acid Effects

RE can be promoted by:

Increasing the bite angle of the ligand

Increasing electrophilicity of metal center (e.g. -acids)
Ligand dissociation

O O F3C
NiII
O O O O
10 mol% O
I
Bu NiII O Bu
O
Pent2Zn Pent
50 mol% Bu
F3C 70% yield, 1h
possible intermediate
w/out -acid: 20%, 15h

Knochel ACIEE 1998 (37) 2387.

M.C. White, Chem 153 Mechanism -26- Week of September 18th, 2012

Organometallic Reaction Mechanisms

3. Transmetallation

LnM X + M'R LnM R + M'-X

X = leaving group (halide, triflate)

M' = usually main group metal (boron, tin, zinc)

Example:

Ph PPh3 Ph PHPh3
Pd + Pd + Bu3SnBr
Bu3Sn
Ph3P Br Ph3P

Topics Discussed

1.What is it? (sigma bond metathesis)

2.Mechanism

3.Complex examples
M.C. White, Chem 153 Mechanism -27- Week of September 18th, 2012

Transmetalation: Definition and Utility

Definition: the transfer of an organic group from one metal

center to another. The process involves no formal change in
oxidation state for either metal. Commonly used transmetalation reagents and their associated
cross-coupling reaction

L'n M' R' + LnM X L'n M' X + LnM R

Transmetalation
R-M1 + X-M2 X-M1 + R-M2
Transmetalation is often a reversible process, with the M2 is typically group 10
equilibrium favoring the more ionic M-X bond. Subsequent
reactivity of one LnM-R species can drive the equilibrium in Reagent R X-coupling reaction
one direction. This is often exploited in cross-coupling LiR, MgXR vinyl, aryl, allyl, alkyl Kumada
reactions, where a transmetalated intermediate undergoes a
RZrClCp2 vinyl, alkyl
reductive elimination to generate a new organic product.
Subsequent oxidative additions generates a new substrate for RZnCl vinyl, aryl, alkyl Negishi
transmetalation
RCuLn alkynyl, aryl e.g. Sonagashira
RSnR'3 vinyl, aryl, alkynl Stille
R
reductive RB(OR')2 vinyl, aryl Suzuki
elimination Ln M (n+2) L'rM' X R-9BBN alkyl Suzuki-Miyaura
R'
transmetalation RSiR'3 aryl, vinyl ,alkyl Hiyama
R R'
L'rM' R' AlR2, AlX2 alkyl

R
M Lr (n)
Lr M (n+2)
X
In generalthe rates of transmetalation of R follow the
order :alkynyl> aryl,vinyl>alkyl
oxidative addition
M= Ni, Pd R X
M.C. White, Chem 153 Mechanism -28- Week of September 18th, 2012
Transmetalation: Mechanism

The mechanism for transmetalation is the least-studied of the basic reaction steps. In a simple picture, the metal
accepting the R group is the electrophile and the M-R bond being transferred is the nucleophile. M-R bond formation
may or may not be simultaneous with M-X bond formation, depending on the nature of X and the actual complexes
involved.

+
M R M R

X M' M' X

With this model, increasing the nucleophilicity of R by altering the ligands on M and increasing the electrophilicity of M
through its ligands will facilitate the transmetalation step. For weakly nucleophilic transmetalation reagents, an added
nucleophile or base often facilitates the transmetalation.

-
R' R' R R
Transmetalation with the -
OR
Suzuki coupling often B B + LnPd II
LnPd
requires added base
OR
RO OR RO
OR X R'
Suzuki Chem. Rev. 1995 (95) 2457.

R R
F- is thought to activate the -
organosilicon reagent for TBAF
R' SiRnF3-n R' SiRnF4-n + LnPd LnPd
transmetalation via
formation of a nucleophilic X R'
pentavalent silicate in a
Hiyama coupling

Hiyama Tet. Lett. 1990 (31) 2719.

M.C. White, Chem 153 Mechanism -29- Week of September 18th, 2012

Transmetalation with advanced intermediates

Suzuki-Miyaura

OBn OBn
H H
O O
9BBN
BnO BnO
OTBS THF, rt
O O O O OTBS
H H H H
BnO H H 9BBN
BnO

OBn
OBn H
H O OBn
O O
OTBS
BnO O OBn
O O H H H
TfO H
H O O
O
BnO H
3M aq. Cs 2CO3, DMF
Pd(Ph3)4, 0C
OBn
71%
Synthetic studies on Ciguatoxin

Takakura ACIEE, 2001 (40) 1090

M.C. White, Chem 153 Mechanism -30- Week of September 18th, 2012

Organometallic Reaction Mechanisms

4. Migratory Insertion / De-insertion

insertion insertion
CO
LnM COR R
LnM LnM
R de-insertion R de-insertion LnM

Example:

CO
Cp2*Nb Cp2 *Nb
Me Cp2*Nb Me
H CO
Nb(III), 18 e- Nb(III), 16 e- Nb(III), 18 e-

Topics Discussed

1.What is it?

2.Mechanism

3.Beta-hydride elimination
 M.C. White, Chem 153 Mechanism -31- Week of September 18th, 2012
Migratory Insertion/De-insertion: Alkyl, H

Cossee-Arlman Mechanism for alkyl migration to a coordinated olefin

CH3
Zr Zr
Zr
CH3 C H
H3

Brintzinger catalyst for Ziegler Natta no oxidation state change at M

polymerizations -2e from the electron count

The -bonding electrons of the olefin are used in -bond formation with a M-alkyl *. Formation of the new C-C and M-C
bonds are thought to occur simultaneously with breaking of the -bond and alkyl-M bond through a 4-centered concerted transition
state. Migratory insertion of a hydride into a coordinated olefin (the microscopic reverse of -hydride elimination) is thought to
procede via the same mechanism. For metal alkyls, the equilibrium lies to the right, whereas for metal hydrides it lies to the left.

Early TS Late TS
Grubbs and Coates Acc. Chem Res. 1996 (29) 85.
M.C. White, Chem 153 Mechanism -32- Week of September 18th, 2012

-Hydride Elimination

A significant decomposition pathway for metal alkyls is -hydride elimination which converts a metal alkyl into a
hydrido metal alkene complex.

+ (BAr '4)- + (BAr '4)-
R R
+ (BAr '4)-
R
N CH3 hydride N CH3 N
Pd II elimination Pd II Pd CH3
N N N H
H H
R R R
donative agostic interaction concerted transition state

-hydride elimination can occur when:

cis to the alkyl group there exists is a site of coordinative unsaturation on the metal which
corresponds to a site of electronic unsaturation (empty metal orbital).
the M-C-C-H unit can take up a coplanar conformation which brings the-hydrogen in close enough
proximity to the metal to form an agostic interaction.
the metal is electrophilic resulting in an agostic interaction that is primarily electron donative in
nature (i.e. -donation>>-backbonding).

H
-donation >>
M
-backbonding
C

-complex
M.C. White, Chem 153 Mechanism -33- Week of September 18th, 2012
Wacker Oxidation

R Binding specificity: terminal olefins

R
Regioselectivity: o2 carbon
H2 O
PdCl2 Remote functionality tolerated
PdCl2
1/2 O2
+ 2 HCl 2 CuCl +
- OH2 OH
Cl 2Pd protonolysis
*
H2 O 2 CuCl2 R *
R
Pd(0)

HCl

H OH
Pd ClPd R
Cl
OH H

R -hydride elimination
O OH HClPd

R R

Commericial production of acetaldehyde

M.C. White, Chem 153 Mechanism -34- Week of September 18th, 2012
-Hydride Elimination

Computational studies suggest that the higher energy of the Ni(II) vacant d orbital (0.1069 hartree) with respect to that of the
analogous Pd(II) complex (0.0505 hartree) results in a weaker donative agostic interaction with the CH bond. The energetically
optimized geometries of the agostic complexes show a greater lengthening of the C-H bond in the Pd(II) complex than in the Ni(II)
complex, indicative of greater -donation in the former. These computational results are consistent the experimentally observed
greater stability of Ni alkyls towards -hydride elimination that Pd alkyls and can be rationalized based on the greater
electronegativity of Pd(II) vs Ni(II) as reflected in their respective second ionization potentials.

1.10 1.13
H H
NiII PH3 Pd II PH3

H H
second ionization potential
Ni(II): 18.15 eV second ionization potential
Pd(II): 19.9 eV
Morokuma JACS 1985 (107) 7109.
recall: sp3 C-H is 1.09
M.C. White, Chem 153 Mechanism -35- Week of September 18th, 2012
Migratory Insertion/De-insertion: CO

Mechanism for CO insertion : via alkyl migration to coordinated CO

O
H3C O
C C
CO
88.2 o H3C 101.3 o
H3C Pd II H Pd II H Pd II H
119.6 o
88.8 o
PH3 PH3 PH3

alkyl groups migrate Computational studies suggest that in the no oxidation state change at M
preferentially over TS, the methyl group has moved up half
hydrides -2e from the electron count
way towards the carbonyl.

Morokuma JACS 1986 (108) 6136.

Experimental evidence also suggests that carbonyl insertion occurs via alkyl migration (not CO migration)

-hydride reductive +
CO
R3P CO R3P insertion R3P elimination R3P elimination O
Pd II Pd II O Pd II O Pd II
R3P -PR3 OC C H C H
H

cis-diethyl complex

CO reductive O
R3P CO R3P R3P
insertion elimination
Pd II Pd II PdII
PR3 -PR3 CO C

O
trans-diethyl complex

Yamamoto Chem. Lett. 1981 289.

M.C. White, Chem 153 Mechanism -36- Week of September 18th, 2012
Migratory Insertion/De-insertion: CO

R3P Cl R3P Cl Cl

PtII PtII PtII

OC R ROC Cl COR

monomer dimer

(no dimer Ph < Me < CH2 Ph < Me < Ph < Et

observed)
Anderson Acc. Chem. Res. 1984 (17) 67.
Electron donating substituents on aryl R groups promote migrations
whereas electron withdrawing substituents inhibit them.

R Monomer Dimer

N 0% 100%

MeO 12% 88%

Me 24% 76%

46% 54%

Cl 73% 27%

NC 100% 0%
Cross J. Chem. Soc., Dalton Trans. 1981, 2317.
M.C. White, Chem 153 Mechanism -37- Week of September 18th, 2012
Heck Arylation

OMe oxidative addition OMe I

OMe OMe
I Pd(L)2
Pd(PPh 3)4 cat.
MeO O NCO2Me NEt3 , CH3CN MeO O NCO2Me
N 80o C N
O O

PPh3 associative displacement

I
PPh3 PPh3
Pd I
MeO
MeO Pd
H migratory insertion OMe
OMe

MeO O NCO2Me
MeO O NCO2Me N
N
reasonable intermediates O
O

-hydride
elimination

OCONH2
MeO
MeO OMe
OMe

MeO O NCO2Me
MeO O NCO2Me N
N
O
O
()-FR-900482
93% yield
Danishefsky JACS 1993 (115) 6094.