Download Reaction Mechanisms

Reaction Mechanisms
Before we get into the synthetic chemistry it is a good idea to first 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
M
L2
+
L1
Both associative (SN2-like) and dissociative (SN1-like) mechanisms are possible
II. Oxidative Addition/Reductive Elimination
often polarized,
"electrophilic"
M(n)
+
oxidative addition
A
B
metal has been
formally oxidized
A
M(n+2)
reductive elimination
usually low-valent (n = 0,1),
"nucleophilic" metal
coordinatively unsaturated
B
M–A and M–B bonds are
usually strong, complex
coordinatively saturated
Reaction Mechanisms
III. Migratory Insertion & Elimination
X
L
L
M Y
M Y
note cis
relationship
X
M Y
X
note empty
coordination site
IV. Nucleophilic Attack on Ligands Coordinated to Metal
reactive to
nucleophiles
(electron-deficient)
M
+
X
Y
X
Y
Nuc–
M
unreactive to
nucleophiles
(electron-rich)
very reactive to other electrophiles,
reactivity increased
if electron-deficeint
M X
Y
Nuc
often this process results in "reductive
elimination" of the metal
Reaction Mechanisms
V. Transmetallation
M1 R
+
M2 X
+
M2 R
M1 X
almost always the rate-limiting step,
usually the culpret when catalytic
processes fail
M1 = Mg, Zn, Zr, B, Hg, Si, Sn, Ge
M2 = transition metal
VI. Electrophilic Attack on Metal Coordinated Ligands
Several different reaction modes are known, will explore further later
M
R
+
E
E
M
R
Nuc–
reductive
elimination
E
R
Nuc
inverstion at R
R
retention at R
attack can directly cleave M–R bond or
can happen α, β, or γ to the metal
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
M
L2
+
L1
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))
Lc
LT
M
X
Lc
square
planar
(16 e–)
+Y
apical
attack
Lc
LT
Y
M
X
Lc
square
pyramidal
(18 e–)
Lc
LT
M
Lc
X
Lc
Y
LT
trigonal
bipyramidal
(18 e–)
Factors that influence the rate:
– identity of the metal
– identy of incoming and outgoing ligands
– identy of the trans ligand ("trans effect")
M
X
Y
Lc
–X
apical
exit
Lc
LT
M
X
Y
Lc
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.
+
L1
M
L2
M
L2
+
L1
Dissociative Mechansim (SN1-like) – typically occurs with 18 electron coordinatively saturated
complexes; often slower that associative substitution; exemplified by M(0) metal carbonyl complexes
– CO
+L
Ni(CO)4
Ni(CO)3
LNi(CO)3
(d10, 18 e–)
(d10, 16 e–)
(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
cone angle (Θ)
R
θ
OMe
OPh
Ph
o-tolyl
Cy
t-Bu
107
128
145
194
170
182
νco (cm-1)
2079
νco (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 νco decreases.
–
2056
2056
Hartwig, Organotransition Metal Chemistry, 2010, pp 37–38.
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 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)
M
M
M
η6-arene
(3 sites)
η4-arene
(2 sites)
η2-arene
(1 site)
+L
Mn(CO)3
Mn(I), d6
18 e–
Mn(CO)3
Mn(I), d6
16 e–
– CO
L
Mn(CO)3
Mn(CO)2L
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
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
O
Common examples: H2, R–H, Ar–H, R3Si–H, R3Sn–H, R2B–H, R3Sn–SnR3, R2B–BR2, RC
H
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.
A–B
LnM
LnM
A
A
A
LnM
B
LnM
B
B
"agostic" interaction
(2 e–, 3 center bond)
cis stereochemistry
(kinetic)
Examples:
OC
Ph3P
Ir
PPh3
Cl
H2
H
Ph3P
Ph3P
Ph3P
Rh
H
Ir
CO
PPh3
Ph3P
Cl
Ph3P
PPh3
Cl
RCHO
Ph3P
Rh
H
PPh3
Cl
PPh3
Rh
R
Ph3P
Cl
O
R2BH
Ph3P
Ph3P
H
Rh
Cl
PPh3
BR2
Oxidative Addition/Reductive Elimination
Polar 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
M
C
X
M(n+2)
C
relative rates:
Me > primary > secondary >> tertiary
I > Br ~ OTs > Cl >> F
phosphines promote with greater basicity giving faster rates
X
X
M C
Oxidative Addition/Reductive Elimination
Polar Electrophiles, cont'd
Examples:
L
OC
Ir
inversion
Cl
CH3I
L
CH3
L
Cl
Ir
L
OC
I
D
Pd(0)
Pt-Bu2Me
H
t-Bu
TsO
H
trans
(kinetic)
Br
Ph
trans
D
t-Bu
H
TsO
D
Br
L2Pd
L2Pd
H
D
L2Pd
Br
L2Pd +
H
Ph
trans
(retention)
Ph
ONa
Ph
Fe(CO)5
d8, 18 e–
Ph
Na2[Fe(CO)4]2–
Collman's reagent
"supernucleophile"
R
X
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.
R
X
hν or
R
O2R
R
+
LnMn
R
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)
+
A
oxidative addition
A
B
M(n+2)
reductive elimination
B
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 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
Ph
Ph
P
Me
Pd
Me
P
Ph
Ph
fast
Me
Me
Me
Ph2P
Pd
Me
Δ
PPh2
no reaction
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
L
L
M Y
M Y
X
M Y
X
General examples:
R
L
+L
LnM
R
LnM
C
C
O
+L
LnM
A
O
B
trans
LnM
A
+L
B
R
L
LnM
A
A
H
trans
cis
R
LnM
H
R
R = aryl, alkyl, H
L
R
B
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.
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.
H
LnM
LnM
LnM
H
H
syn coplanar
BHE from transition metal-alkoxides and -amines are also important
Me
O
LnM
Me
H
O
LnM
Me
+L
Me
H
O
L
LnM
H
+
M–H without using H2
β-Eliminations of alkoxides and halides are known.
Me
Me
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.
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.
H
LnM
H
H
H
LnM
Often induced by ligand exchange processes.
Cp
Me3P
V
t-Bu
t-Bu
+
Me
Me2P
PMe2
Me Cp
V
P
P
Me
Me
t-Bu
+ tBuCH3 + PMe3
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 Metal-Bound Carbonyl – The nucleophile is typically strong nucleophiles, like RLi
LnM C
O
RLi
O
LnM
Ln is good π-acceptor
(another CO)
usually quite stable and can
be further manipulated
R
acyl "ate" complex
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.
X
L
L
ROH
Pd
Ar
PdLn
O
+
ArCO2R
Nuc
Nuc–
M
M
+
HX
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.
Nuc
Nuc–
"external" addition of nucleophile
product of anti addition
(most common pathway)
M
M
Nuc–
insertion
M
Nuc
"internal" addition of nucleophile
product of syn addition
M
Nuc
Other nucleophilic reactions will be covered as needed
Transmetallation
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.
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 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.
R
R
L
Pd
L
C
SnBu3
L
Pd
C
X
SnBu3
L
X
proposed open t.s.
leading to inversion
similar mechanisms could be drawn
with other metals under apprpriate
activation
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
specific examples will be discussed as needed.
Electrophilic cleavage of σ-alkyl metal bonds – Note metal is removed.
R
+
M
E+
Fe(CO)2Cp
Me
R
M+
+
E
retention at R
DCl
D
Me
+
CpFe(CO)2Cl
Attack at α-position – Forms carbenes
Ph
M CHPh +
Ph3C+
H
M C
Ph
M C
R
+
H
H
TfO–
TMSOTf
OC
OC
Fe
CH2OH
M C
H+
CH2Cl2
–90 ºC
OC
OC
Fe
+
CH2
Me3SiOH
Electrophilic Attack on Coordinated Ligands
Several different reactivity modes depending on the metal, ligand, and electrophile involved. More
specific examples will be discussed as needed.
Attack at β-position
M
H
+ Ph3C+
M
M
E
E+
+
M
R
M
R
E+
+
M C
E
vinylidene
MeOTf
OC
Mn
OC
Mn
C
Me
OC
OC
CO2Me
O
CO2Me
O
OMe
Me3OBF4
(OC)5W
(OC)5W
Ph
(OC)5W
Ph
Ph
Electrophilic Attack on Coordinated Ligands
Several different reactivity modes depending on the metal, ligand, and electrophile involved. More
specific examples will be discussed as needed.
Attack at γ-position
M
+ E+
R2
R1
+ R3CHO
SnBu3
M
+
R2
OH
PdCl2(PPh3)2
R3
likely involves formation of
M
E
A
η1-allyl
M
B
R1
intermediate
B
A
Cp(CO)3Mo
Cp(CO)3Mo
+
ArSO2NCO
Me
Me
B
M
A
N
O
SO2Ar