Reaction Mechanisms

Before we get into the synthetic chemistry it is a good idea to rst become familiar with some of 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
M L1

L2

L2

L1

Both associative (SN2-like) and dissociative (SN1-like) mechanisms are possible II. Oxidative Addition/Reductive Elimination often polarized, "electrophilic" oxidative addition
A B

metal has been formally oxidized

A M(n+2)

M(n)

reductive elimination usually low-valent (n = 0,1), "nucleophilic" metal coordinatively unsaturated

MA and MB bonds are usually strong, complex coordinatively saturated

Reaction Mechanisms
III. Migratory Insertion & Elimination
X M Y M Y X

L M Y X

note cis relationship

note empty coordination site

IV. Nucleophilic Attack on Ligands Coordinated to Metal reactive to nucleophiles (electron-decient) Nuc
M X Y Nuc

very reactive to other electrophiles,

M unreactive to nucleophiles (electron-rich) reactivity increased if electron-deceint

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, Ge M2 = transition metal

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

VI. Electrophilic Attack on Metal Coordinated Ligands Several different reaction modes are known, will explore further later

Nuc

Nuc

reductive elimination
E R

inverstion at R

attack can directly cleave MR bond or can happen , , or to the metal

retention at R

Ligand Substitution
Though 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.
M L1

L2

L2

L1

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

Lc LT

X Lc

+Y apical attack

Lc LT

X Lc

X Y

Lc LT

M X

Y Lc

X apical exit

Lc LT

M X

Y Lc

square planar (16 e)

square pyramidal (18 e)

trigonal bipyramidal (18 e)

Factors that inuence the rate: identity of the metal identy of incoming and outgoing ligands identy of the trans ligand ("trans effect")

Ligand Substitution
Though 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.
M L1

L2

L2

L1

Dissociative Mechansim (SN1-like) typically occurs with 18 electron coordinatively saturated complexes; often slower that associative substitution; exemplied by M(0) metal carbonyl complexes CO Ni(CO)4 (d10, 18 e) Ni(CO)3 (d10, 16 e) +L LNi(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. R
R R P M R

107 128 145 194 170 182

co (cm-1)
2079 co (cm-1) is determined with Ni(CO)3L and is a 2085 measurement of the amount of backbonding. More 2069 donating L, more backbonding and co decreases. 2056 2056

cone angle ()

OMe OPh Ph o-tolyl Cy t-Bu

Hartwig, Organotransition Metal Chemistry, 2010, pp 3738.

Ligand Substitution
A "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 3-allyl, 5-cyclopentadienyl, and 6-arene complexes. By slipping to a lower hapticity, a coordination site (or two) is opened.

3-allyl (2 sites)

1-allyl (2 sites)

6-arene (3 sites)

4-arene (2 sites)

2-arene (1 site)

+L
Mn(CO)3 Mn(CO)3 L Mn(CO)3

CO
Mn(CO)2L

Mn(I), d6 18 e

Mn(I), d6 16 e

Oxidative Addition/Reductive Elimination

Reactions 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).
M(n)

oxidative addition
A B

A M(n+2)

reductive elimination

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). -Donor ligands (PR3, R, and H) facilitate OA. -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
O H

Common examples: H2, RH, ArH, R3SiH, R3SnH, R2BH, R3SnSnR3, R2BBR2, RC

Generally undergo OA by concerted, one-step "insertion" mechanism. The conguration of any stereocenters would be expected to be retained. May require dissociation of a ligand from the initial complex. LnM AB LnM
A B A A

LnM

LnM
B

"agostic" interaction (2 e, 3 center bond) Examples:

OC Ph3P PPh3 Cl

cis stereochemistry (kinetic)

Ir

H2

H Ph3P

H Ir CO

PPh3 Cl

Ph3P Ph3P

Rh

PPh3 Cl

R2BH

Ph3P Ph3P

H Rh Cl

PPh3 BR2

Ph3P Ph3P

Rh

PPh3 Cl

RCHO

Ph3P

PPh3 Rh R Ph3P Cl O

Oxidative Addition/Reductive Elimination

Polar Electrophiles Common examples: HX, X2, RX, R(O)X, ArX, 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 conguration of any stereocenters would be expected to be inverted in this case. The structure of the electrophile determines which is active.

Mn

M(n+2)

M C

relative rates: Me > primary > secondary >> tertiary I > Br ~ OTs > Cl >> F phosphines promote with greater basicity giving faster rates

Oxidative Addition/Reductive Elimination

Polar Electrophiles, cont'd Examples:
L OC Cl L

inversion CH3I
CH3 L Cl Ir L OC I D TsO H D H t-Bu

Ir

Pd(0) Pt-Bu2Me
L2Pd TsO

D t-Bu H D

trans (kinetic)

Br

Br

L2Pd +

Br

Ph

L2Pd
H Ph

L2Pd trans (retention)

Ph

trans
ONa Ph Ph

Fe(CO)5 d8, 18 e

Na2[Fe(CO)4]2 Collman's reagent "supernucleophile"

Na[RFe(CO)4] Further reactions possible

Oxidative Addition/Reductive Elimination

Polar 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.

h or O2R

LnMn

M(n+1)Ln

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

+ R

sequential 1e oxidations, net 2e oxidation of metal

Oxidative Addition/Reductive Elimination

M(n)

oxidative addition
A B

A M(n+2)

reductive elimination

Reductive Elimination (RE) The reverse of oxidative addition. Concerted mechanism proceeds with retention of any stereochemical information. Nucleophilic attack on the ligand would invert the conguration. Factors that inuence: 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

Ph P

Ph Me Pd P Me Ph

fast

Me Me Me Ph2P Pd Me PPh2

no reaction

Ph

Migratory Insertion & Eliminations

Migratory Insertion 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.
X M Y M Y X

L M Y X

General examples:
R LnM C O R

+L
LnM

L C O LnM A

R B

+L

L LnM A H

R H B

R = aryl, alkyl, H

trans cis
R LnM A B

trans

+L
LnM A

R B

Migratory Insertion & Eliminations

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. -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 -hydrogens usually must be syn coplanar to the metal. Also the metal usually must have an open coordination site.

H LnM LnM H LnM H

syn coplanar BHE from transition metal-alkoxides and -amines are also important
Me O LnM Me O LnM Me Me H

+L

L LnM H

+
Me Me

MH without using H2 -Eliminations of alkoxides and halides are known.

Migratory Insertion & Eliminations

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. -Hydride Elimination (AHE) Elimination of an -hydrogen from metal alkyl complexes. This forms a carbene. Much slower than -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.

H LnM

H LnM

Often induced by ligand exchange processes.

Cp Me3P V t-Bu Me Cp P P Me V Me t-Bu

Me Me2P PMe2

+ tBuCH3 + PMe3

t-Bu

Nucleophilic Attack on Coordinated Ligands

Many different kinds of examples of this. From our prespective the more important ones involve attack on MCO complexes and Malkene/alkyne complexes. Attack on Metal-Bound Carbonyl The nucleophile is typically strong nucleophiles, like RLi RLi
LnM O R

LnM C

usually quite stable and can be further manipulated

Ln is good -acceptor (another CO)

acyl "ate" complex

Attack on MC -Bonds Such bonds are often intermediates in catalytic reactions. The carbon can be sp2 or sp3 hybridized. Nucleophilc reactions with 3-allyl complexes fall in this category. Can also be considered as a "reductive elimination" process.
X L L Pd O Ar

ROH

PdLn

ArCO2R
Nuc

HX

Nuc
M M

Nucleophilic Attack on Coordinated Ligands

Many different kinds of examples of this. From our prespective the more important ones involve attack on MCO complexes and Malkene/alkyne complexes. Attack on MC -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. Nuc
M M Nuc

"external" addition of nucleophile product of anti addition (most common pathway)

Nuc insertion
M Nuc M Nuc

"internal" addition of nucleophile product of syn addition

Other nucleophilic reactions will be covered as needed

Transmetallation
Importance is growing as this is a key step in useful methods for constructing CC bonds, particularly such bonds that are difcult 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.
M1 R

M2 X

M2 R

M1 X

M1 = Mg, Zn, Zr, B, Hg, Si, Sn, Ge M2 = transition metal 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 benet. Often this can be enhanced by appropriate "activation" of the main group element. Isomeric integrity (cis, trans) is usually maintained when R is an olen. With alkyl metals the situation is more complicated. With polar solvents, alkylstannanes can transmetallate with inversion of conguration (open transition state?), but in less polar solvents retention is seen (closed transition state?). However, aliphatic organoboron reagents tend to proeed with retention.
R L Pd L X C SnBu3 L X SnBu3 Pd R L C

similar mechanisms could be drawn with other metals under apprpriate activation

proposed open t.s. leading to inversion

proposed open t.s. leading to retention

Electrophilic Attack on Coordinated Ligands

Several different reactivity modes depending on the metal, ligand, and electrophile involved. More specic examples will be discussed as needed. Electrophilic cleavage of -alkyl metal bonds Note metal is removed.
R M

E+

M+

retention at R

Me

Fe(CO)2Cp

DCl
Me

CpFe(CO)2Cl

Attack at -position Forms carbenes

Ph M CHPh + Ph3C+ H M C H M C R Ph

H+

M C H

TMSOTf
OC OC Fe CH2OH

TfO
OC OC Fe

CH2Cl2 90 C

+
CH2

Me3SiOH

Electrophilic Attack on Coordinated Ligands

Several different reactivity modes depending on the metal, ligand, and electrophile involved. More specic examples will be discussed as needed. Attack at -position
M

+ Ph3C+

E+
R

E M

E+

M C E

vinylidene

MeOTf
OC OC Mn CO2Me

OC OC

Mn

Me CO2Me

O (OC)5W Ph (OC)5W

O Ph

Me3OBF4
(OC)5W

OMe Ph

Electrophilic Attack on Coordinated Ligands

Several different reactivity modes depending on the metal, ligand, and electrophile involved. More specic examples will be discussed as needed. Attack at -position
M

+ E+

E OH R3 R2

R2 R1 SnBu3

+ R3CHO

PdCl2(PPh3)2

likely involves formation of

1-allyl

intermediate

R1

A B M

B A Cp(CO)3Mo

B A SO2Ar

Cp(CO)3Mo

+
Me

ArSO2NCO
Me

N O