6 reaction mechanisms
TRANSCRIPT
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Reaction Mechanisms
Before 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 elimination
M(n+2)
A
B
usually low-valent (n= 0,1),"nucleophilic" metal
coordinatively unsaturated
often polarized,"electrophilic"
MA and MB bonds areusually strong, complexcoordinatively saturated
metal has beenformallyoxidized
Both associative (SN2-like) and dissociative (SN1-like) mechanisms are possible
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M
Reaction Mechanisms
III. Migratory Insertion & Elimination
IV. Nucleophilic Attack on Ligands Coordinated to Metal
M Y M Y
X
X M Y XL L
note cisrelationship
note emptycoordination site
M X Y+ X YNuc
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 "reductiveelimination" of the metal
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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 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 MR bond orcan happen , , or to the metal
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Ligand Substitution
Though we will be concerning ourselves more with the reactivity and synthetic utility of organimetalliccomplexes, 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
MY
X
Lc
Lc
LT MLT Lc
Lc Y
X
MLT Lc
Lc Y
X
X
apicalexit
Factors that influence the rate:
identity of the metal identy of incoming and outgoing ligands identy of the transligand ("trans effect")
squareplanar(16 e)
squarepyramidal
(18 e)
trigonalbipyramidal
(18 e)
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Ligand Substitution
Though we will be concerning ourselves more with the reactivity and synthetic utility of organimetalliccomplexes, 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 saturatedcomplexes; often slower that associative substitution; exemplified by M(0) metal carbonyl complexes
M L1 L2+ M L2 L1+
Ni(CO)4
(d10, 18 e)
CO
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 isparticularly 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 ()
R
OMe 107OPh 128
Ph 145o-tolyl 194
Cy 170
t-Bu 182
co (cm-1)
20792085
2069
2056
2056
co (cm-1) is determined with Ni(CO)3L and is a
measurement of the amount of backbonding. Moredonating L, more backbonding and co decreases.
Hartwig, Organotransition Metal Chemistry, 2010, pp 3738.
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M
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.
M M
3-allyl
(2 sites)
1-allyl
(2 sites)6-arene
(3 sites)
M
4-arene
(2 sites)
M
2-arene
(1 site)
Mn(CO)3Mn(CO)3
Mn(I), d6
18 eMn(I), d6
16 e
+ L
Mn(CO)3L
CO
Mn(CO)2L
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Oxidative Addition/Reductive Elimination
Reactions of this type are central to the synthetic utility of transition metals complexes and relieson the ability of metals to easily and reversably change oxidation states (compare to what is
takes to change oxidation state of C).
M(n) + A Boxidative addition
reductive elimination
M(n+2)
A
B
The terms "oxidative addition" and "reductive elimination" are generic and refer only to the process ofchanging 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 aboveprocess (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.
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Oxidative Addition/Reductive Elimination
Nonpolar Electrophiles
Common examples: H2, RH, ArH, R3SiH, R3SnH, R2BH, R3SnSnR3, R2BBR2,
Generally undergo OA by concerted, one-step "insertion" mechanism. The configuration of anystereocenters would be expected to be retained. May require dissociation of a ligand from the
initial complex.
LnMAB
LnMB
A
"agostic" interaction(2 e, 3 center bond)
cisstereochemistry(kinetic)
Examples:
LnM
A
B
LnMA
B
RC
O
H
Ph3P
IrCl
OC PPh3 H2
Ph3P
Ir
Cl
H PPh3H
COPh
3P
RhCl
Ph3P PPh3
Ph3P
Rh
BR2
Ph3P PPh3H
Cl
R2BH
Ph3PRh
Cl
Ph3P PPh3
Ph3PRh
Ph3P PPh3H
Cl
RCHO
O
R
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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 (directinsertion). 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 wouldbe 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
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Oxidative Addition/Reductive Elimination
Polar Electrophiles, cont'd
Examples:
OCIr
L
L Cl
OCIr
L
L ClCH3
I
CH3I
trans(kinetic)
TsOt-Bu
D H
H D
L2Pdt-Bu
H D
H DTsO
Pd(0)Pt-Bu2Me
L2Pd PhBr+
inversion
L2PdBr
PhHtrans
PhL2Pd
Br
trans(retention)
Fe(CO)5
d8, 18 e
PhPh
ONa
Na2[Fe(CO)4]2
Collman's reagent"supernucleophile"
R XNa[RFe(CO)4]
Further reactions possible
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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 Xh or
O2RR
R + LnMn R M(n+1)Ln
R M(n+1)Ln RX+ R M(n+2)Ln
X
R+
sequential 1e oxidations,
net 2e oxidation of metal
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Oxidative Addition/Reductive Elimination
M(n) + A Boxidative addition
reductive elimination
M(n+2)
A
BReductive Elimination (RE)
The reverse of oxidative addition. Concerted mechanism proceeds with retention of anystereochemical 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
P
Pd
P Me
Me
Ph Ph
Ph Ph
fastMe Me PPh2Ph2P Pd
Me
Me
no reaction
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Migratory Insertion & Eliminations
Migratory Insertion
M Y M Y
X
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:
LnM
R
C
O
LnM
L
C
R = aryl, alkyl, H
+ L
O
R
LnM
R LnM
L+ L
A B A H B
R
H
trans trans
LnM
R
LnM
L+ L
B
A
R
BA
cis
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Migratory Insertion & Eliminations
-Hydride Elimination (BHE)
If an alkyl metal complex has hydrogens b to the metal, then this type of elimination is likely tooccur. However, the -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.
H
LnM
syn coplanar
LnM HLnM H
BHE from transition metal-alkoxides and -amines are also important
O
HLnM
Me
Me
LnM H
O MeMe
LnM H
L+ L
Me
O
Me
+
MH without using H2
-Eliminations of alkoxides and halides are known.
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Migratory Insertion & 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.
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 H
LnMHH
Often induced by ligand exchange processes.
V
Cp
Me3P
t-Bu
t-Bu
PMe2Me2P+ V
Cp
P
PMe
Me
MeMe
t-Bu + tBuCH3 + PMe3
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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 onesinvolve attack on MCO complexes and Malkene/alkyne complexes.
LnM C O
Ln is good -acceptor(another CO)
RLi
LnM R
O
acyl "ate" complex
usually quite stable and canbe further manipulated
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.
ArPd
O
L
L
X ROHPdLn ArCO2R+ + HX
Nuc
Nuc
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Nucleophilic Attack on Coordinated Ligands
Many different kinds of examples of this. From our prespective the more important onesinvolve 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, theaddition can be synor anti.
M
Nuc
M
Nuc"external" addition of nucleophileproduct of antiaddition(most common pathway)
M Nuc
insertion
M
"internal" addition of nucleophileproduct of synaddition
Nuc
Other nucleophilic reactions will be covered as needed
Nuc
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Transmetallation
M1 R M2 X+ M2 R M1 X+
M1 = Mg, Zn, Zr, B, Hg, Si, Sn, Ge
M2 = transition metal
Importance is growing as this is a key step in useful methods for constructing CC bonds, particularlysuch 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. Oftenthis 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 situationis more complicated. With polar solvents, alkylstannanes can transmetallate with inversionof
configuration (open transition state?), but in less polar solvents retentionis seen (closed transitionstate?). However, aliphatic organoboron reagents tend to proeed with retention.
Pd
R
XL
L
C SnBu3
proposed open t.s.leading to inversion
Pd
R
XL
L
C
SnBu3
proposed open t.s.leading to retention
similar mechanisms could be drawnwith other metals under apprpriate
activation
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Fe
Electrophilic Attack on Coordinated Ligands
Several different reactivity modes depending on the metal, ligand, and electrophile involved. Morespecific examples will be discussed as needed.
Electrophilic cleavage of -alkyl metal bonds Note metal is removed.
R M + E+ R E + M+ retention at R
MeFe(CO)2Cp Me
DDCl
CpFe(CO)2Cl+
Attack at -position Forms carbenes
M CHPh
H
+ M C
H
Ph
M C R + M C
H
Ph
H+Ph3C+
OC
OCCH2OH
Fe
OC
OCCH2
TMSOTf
CH2Cl290 C
TfO
+ Me3SiOH
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Electrophilic Attack on Coordinated Ligands
Several different reactivity modes depending on the metal, ligand, and electrophile involved. Morespecific examples will be discussed as needed.
Attack at -position
+ + E+Ph3C+
HM M M M
E
M R + E+ M C
E
R
vinylidene
Mn
OC
OCMn
OC
OCC
MeOTf
CO2Me
Me
CO2Me
(OC)5W Ph
O
(OC)5W Ph
O Me3OBF4(OC)5W
Ph
OMe
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Electrophilic Attack on Coordinated Ligands
Several different reactivity modes depending on the metal, ligand, and electrophile involved. Morespecific examples will be discussed as needed.
Attack at -position
+ E+M ME
+M MA
A
B
BM
A
B
SnBu3
R2
R1+ R3CHO
PdCl2(PPh3)2
R3
OH
R1
R2
likely involves formation of 1-allyl intermediate
Cp(CO)3Mo
Me
ArSO2NCO+N
Me
Cp(CO)3Mo
O
SO2Ar