Shaughnessy Omets Notes

Organometallic Chemistry of the Transition Metals: Mechanisms
and Applications to Catalysis
Kevin H. Shaughnessy
Department of Chemistry & Biochemistry
The University of Alabama, Tuscaloosa, AL
kshaughn@ua.edu
kshaughnessy.people.ua.edu
Updated fall 2019

2
These notes have been prepared by Dr. Kevin Shaughnessy, Professor of Chemistry & Biochemistry at
The University of Alabama for use in CH 409/609, Organometallic Chemistry. These notes are designed
to be stand alone, but can be supplemented with any organometallic textbook, such as those by Hartwig,
Crabtree, or Spessard. These materials may be freely used without permission provided that credit to the
author is given and they are not altered or incorporated into other materials without permission from the
author.
Updated versions of these notes can be found at: http://kshaughnessy.people.ua.edu/resources.html
Table of Contents
1. Structure and Bonding .............................................................................................................................. 3

2: Survey of Ligand Types--Part 1 (L-type ligands) .................................................................................... 21
2: Survey of Ligand Types--Part 2 (X-type ligands) .................................................................................... 37
3-Ligand Substitution .................................................................................................................................. 49
4-Oxidative Addition/Reductive Elimination ................................................................................................ 57
4-Oxidative Addition/Reductive Elimination: Part 2 ................................................................................... 69
5-Migratory Insertion and Elimination ......................................................................................................... 83
6-Metal-Ligand Multiple Bonds ................................................................................................................... 95
7-Nucleophilic and Electrophilic Attack on Ligands .................................................................................. 104
8-Catalysis General Principles ................................................................................................................. 115
9 Cross-Coupling Reactions ..................................................................................................................... 119
10-Hydrocarbon Functionalization by C-H Activation ............................................................................... 148
11-Hydrogenation of Unsaturated Compounds ........................................................................................ 163
12-Carbonylation Reactions ..................................................................................................................... 172
13-Insertion Polymerization and Oligomerization of Alkenes, Part 1: Early Transition Metals ................ 184
13-Insertion Polymerization and Oligomerization of Alkenes, Part 2: Late Transition Metals ................. 196
14-Alkene and Alkyne Metathesis ............................................................................................................ 206
Kevin Shaughnessy
The University of Alabama, 2019
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1. Structure and Bonding
Basic Picture of Metal-Ligand Bonds
As we'll discuss, there are a wide variety of metal-ligand bonding interactions. They can nearly all be
described as a Lewis acid-Lewis base interaction, however. The ligand will generally act as an electron
pair donor (Lewis base) with the metal acting as an electron pair acceptor (Lewis acid). The resulting
bond will have significant covalent character, but is unique from the covalent bonds described for main
group elements like carbon. When we think about bond dissociation of a C-H bond, for example, we
mean hemolysis to a carbon and hydrogen radical. When discussing metal-ligand bond energies, we are
referring to cleavage in which the ligand retains the electron pair.
M + L M L
Types of Ligand Coordination
Three generic classes of ligands:

L: a neutral electron pair donor (i.e., CO, PR3)
X: an anionic electron pair donor (i.e., X-, H-)
Z: electron pair acceptor (Lewis acid)
M-M: neutral 1 electron donor
Distinguishing L-type ligands from X-type ligands: To distinguish between X and L type ligands, consider
removing ligand from metal center with the ligand taking the electron pair in the M-L bond. If the ligand in
it's free state is neutral, it is an L-type ligand. If it would be anionic, it is X-type.
CH3 X-type
CH3
L-type N N Pd PMe3 PMe3 L-type
Cl
Cl— X-type
Ligands that can donate more than one pair of electrons can be classified using L and X designations:
CH3
O H3C CH3
L2 N
4 e donor R H3C CH3
LX
4 e donor L2X
6 e donor
Z-type ligands are less common, but have attracted increasing attention. In the case of a Z-type ligand,
the metal is the electron pair donor and the ligand is an electron acceptor. These can be more difficult to
recognize. Typical Z-type coordinating atoms will be typical Lewis acidic elements (B, Al, Ga, In, Si, Sn,
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Sb, etc) where location of a lone pair on the coordinating atom does not make sense. Z-type ligands are
generally weakly coordinating, so the known examples are part of chelating ligand systems. The metals
are typically low valent, late transition metals (Pd(0), Pt(0), Au(I)).
AuII Cl Au(II) rare oxidation state
M + Z M Z Cy2B Pi-Pr2
Cl
Au LX
Cy2B Pi-Pr2 Anionic B(II) unlikely
X
L L AuI Cl Au(I) common

Cl Z
Cl Cy2B Pi-Pr2
Ph2P Pd PPh2 Cl
Sb LZ
Cl B(III) as Lewis acid
N Ga N Cl
Cl N
Ph2P Au PPh2
L Cl L
Z
X
Pd(0), Ga(III) Au(I), Sb(V)
Types of ligand coordination:
Terminal: Ligand is bound to only one metal center (L-M or X-M)
Bridging (µ): Ligand is attached to two different metal centers (M-L-M’ or M-X-M’). For L-type
ligands, the lone pair is usually shared between the two metals (count 1 electron for each metal).
For X ligands, the lone pair can also be shared. If the X ligand has additional lone pairs (i.e.,
halide, alkoxide), then the additional lone pairs can be used to coordinate to the second metal
center.
Hapticity (h): Ligand attached to a metal center through more than one atom without non-
coordinating atoms in between. Most commonly seen with conjugated π-systems
M M M
η4 η5 η6
Hapticity for ligands such as Cp can be variable depending on how it is coordinated. Usually Cp
is a h5-L2X ligand, but it can also coordinate as an h3-LX, or even an h1-X. The process of going
from h5 to h3 is called ring slippage.
Chelation: Ligand attached through more than one atom usually separated by one or more
atoms. Chelating ligands are sometimes classified as being bidentate (2 points of attachment),
tridentate (three points of attachment), or tetradentate (4 points of attachment).
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Me2
N Cl Fe
S
Pt S S
N Cl P κ4P,S,S,S-coordination
Me2 tetradentate ligand
κ2N,N-coordination
bidentate ligand
Kappa convention (k): The kappa convention is sometimes used to indicate the coordinating
atoms of a polydentate ligand. If only some of the possible coordination sites are bonded to the
metal, the coordinating atoms are indicated with a kappa. Some authors use kappa to indicate
how many of the coordinating atoms are attached in a polydentate ligand.
κ3-[N,N'-di(2-aminoethyl)ethane 1,2-
NH diamine]chloroplatinum ion
or
Pt
N NH [N-(2-amino-κN-ethyl)-N'-(2-
H2 Cl NH2 aminoethyl)ethane 1,2-diamine-
κ2N,N']chloroplatinum ion
The 18-Electron Rule
Recall: Second row elements (B, C, N, O, F) have 4 valence orbitals (1 s + 3 p) so they can
accommodate up to 8 valence electrons--the octet rule.
Transition metals have 9 valence orbitals (1 s + 3 p + 5 d). Upon bonding to a ligand set, there will be a
total of 9 low lying orbitals (see MO theory discussion below). Therefore, we can expect that the low lying
MOs can accommodate up to 18 valence electrons--The 18-Electron Rule. Organometallic complexes
with 18 electrons are predicted to be particularly stable because they will have a closed shell of electrons.
Complexes with 18 electrons are often referred to as being coordinatively saturated.
Counting electrons: There are two models for counting electrons. Both give the same answer, but offer
different advantages and disadvantages.
Example: CH4
Covalent model: Since C-H bonds are covalent, assume that the electrons are shared equally between
carbon and hydrogen. To count the electrons, we dissect the molecule giving each atom 1 electron of the
bonding pair.
H
H: 4 X 1 e = 4
H C: 4e
H C H H C H Total = 8 electrons
H
H
Ionic model: Alternatively, we can treat the bonds as being ionic. This allows us to assign a formal
oxidation state to the carbon atom. This can be useful to determine whether a particular transformation is
an oxidation or a reduction. In this model, both electrons are given to the atom with the higher
electronegativity. For a C-H bond, this is the carbon.
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H
H H+: 4 X 0 e = 0
H C H H C 4-
H C(-4): 8 e
Total = 8 electrons
H
H
Similarly for a transition metal complex, the electron count is the sum of the metal valence electrons + the
ligand centered electrons.
Covalent Model: # e = # metal electrons (zero valent) + # ligand electrons - complex charge
Metal: The number of metal electrons equals its column number (i.e., Ti = 4e, Cr = 6 e, Ni = 10 e)
Ligands: In general L donates 2 electrons, X donates 1 electron. See the table below.
Ionic Model: # e = # metal electrons (dn) + # ligand electrons
Metal: Determined based on the number of valence electrons for a metal at the oxidation state
present in the complex
Ligands: In general and L and X are both 2 e donors. See the table below.
In my opinion, the ionic model is easier and gives a clearer picture of the actual chemistry, since the
formal oxidation state is part of the calculation. All discussions in this class will use the ionic model, so I
would encourage you to learn that one. You should also be aware of the covalent method, since you will
encounter it from time to time.
Metal oxidation states: The oxidation state of a metal can be simply determined by adding up the total
charge for the free ligands (each X ligand is -1). If the complex is neutral, the metal must have a positive
charge to match the total negative charge of the ligands. If the complex has an overall charge, this must
be considered.
Ti(CH3)4: The methyl groups have -1 charges, so the total ligand charge is -4. Therefore the titanium
center must match that and be +4.
[Pd(NH3)Cl3]–: There is a total -3 charge on the ligands (3XCl–), but the complex has an overall negative
charge. Therefore, the metal is Pd(+2).
d electron count: Chemists often refer the d-electron count of a metal. This indicates the number of
valence electrons. For an isolated, zero-valent transition metal the s orbitals of the next row are lower in
energy than the d orbitals. Thus, the configuration of Ni(0) could be written as [Ar]4s23e8. In reality, the
4s and 3d (or 5s/4d or 6s/5d) orbitals are very close in energy. When a metal interacts with other ligands,
the d orbitals are almost always lower in energy than the s orbitals of the next row, which is a M-L σ*
orbital. Thus, for our purposes the d electron count for a zero-valent metal will always just be its column
number. For a metal ion, it will be the column number minus the formal oxidation state. Thus Ni(0) would
be d10 and Ni(II) would be d8.
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Examples:
HMn(CO)5
Covalent Model H Ionic Model

OC CO
•H = 1 e Mn H– = 2 e
5 X CO = 10 e OC CO 5 X CO = 10 e
Mn = 7 e Mn(I) d6 = 6 e
CO Total = 18 e
Total = 18 e
[CpFe(CO)]-
Covalent Model Ionic Model
Cp• = Cp– =
2 X CO = 2 X CO =
Fe = Fe Fe(0) d8 =
Charge (-1) = Total =
Total = OC
CO
[CpNi(µ-CO)]2
Covalent Model O Ionic Model

C
Cp• = Cp Ni Cp- =
Ni Cp
2 X 1/2 CO = 2 X 1/2 CO =
Ni-Ni = C Ni-Ni =
Ni = O Ni(I) d9 =
Total = Total =
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Ligand Name Covalent Model lonic Model
Electron
Electron Count Charge
Count
Nitrosyl (linear, NO+), terminal or bridging) 3 +1 2
Carbene (CYR, where Y = substituent with π

interaction with carbene, i.e., OR, NR2, Ph, X
2 0 2
Y
M
R
CO, CNR (bridging or terminal) 2 0 2
PR3, AsR3, SbR3, NR3, imines, nitriles, ethers,

2 0 2
sulfides, etc.
Terminal dinitrogren (N2) 2 0 2
2 0 2
h2(π)-Alkene M
2 0 2
h2(π)-Alkyne M
O
M 2 0 2
h2(π)-Carbonyl
H H
2 0 2
h2(s)-Dihydrogen M
4 0 4
µ-h2-Alkyne M M
h4-acyclic diene
4 0 4
6 0 6
h6-Arene M
Hydride (H-) 1 -1 2
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Terminal or bridging Alkyl (-CR3) 1 -1 2
O
1 -1 2
h1-Acyl M
h1-Aryl, alkenyl, or alkynyl 1 -1 2
ER3 or EX3 (E = Si, Ge, Sn) 1 -1 2
Alkoxide (-OR), thiolate (-SR), amide (-NR2), or

1 -1 2
phosphide (-PR2)
O 1 -1 2
Superoxide M O
Halide (F-, Cl-, Br-, I-) or pseudohalide (-CN, -OTs, etc) 1 -1 2
Bridging alkoxide, thiolate, amide, or phosphide 3 -1 4
Bridging Halide (µ-X)

3 -1 4
M-X-M
O
3 -1 4
h2-Acyl M
h2-Alkenyl (terminal or bridging)

M
M M 3 -1 4
Terminal Bridging
M 3 -1 4
h3-Allyl
5 -1 6
h5-Cyclopentadienyl (Cp-) M
Carbene (CR2 where R = substituent with no π

R
2 -2 4
M
interactions with the carbene carbon) R
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C 2 -2 4
M
µ-CYR or CR2 R M
Imide (M=NR) 2 -2 4
Oxide (M=O) 2 -2 4
M
2 -2 4
Peroxide (terminal or bridging) O O
Alkylidine or carbyne, terminal M C R 3 -3 6
C 3 -3 6
M
µ-Alkylidine M M
Nitride M N 3 -3 6
Application of the 18-electron rule:
The 18-electron rule can be used as predictor for the number of ligands a particular metal will coordinate.
V(CO)6 Cr(CO)6 (CO)5Mn-Mn(CO5 Fe(CO)5 (CO)3Co(µ-CO)2Co(CO)3 Ni(CO)4
d5 d6 d7 d8 d9 d10
17 e 18 e 18 e 18 e 18 e 18 e
The 18 electron rule works best for low-valent metals with small ligands that are strong s donors and/or π
acceptors (i.e., H– and CO). The types of ligands are strongly coordinating and are small enough to allow
the metal to be coordinatively saturated.
For complexes that follow the 18 electron rule, it can be used to predict reactivity as we will see
throughout the semester.
Note, that just like the octet rule, the 18-electron rule is not an absolute requirement. There are many
exceptions, particularly for metals that have fewer than 18 electrons. Exceeding the 18 electron rule is
rare and often involves changes that bring the electron count to 18 or below.
Common exceptions to the 18 electron rule:
d8 metals: The d8 metals (groups 8 - 11) have a tendency to form square-planar 16 electron
complexes. This tendency is weakest for group 8 (Fe(0), Ru(0), and Os(0)) and is very strong for
groups 10 and 11 (Pd(II), Au(III)). Square planar, 16 electron complexes of d8 metals have 4 low
lying d orbitals that can be filled by the 8 d-electrons.
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PMe 3 CO CH3
Me Pd Me Me3P Rh Cl Me3P Au CH3

PMe 3 CO CH3
d0 metals: The high-valent d0 complexes often have lower electron counts than 18. It is difficult
for these metals to coordinate enough ligands to get to 18 electrons. An exception is [ReH9]2-.
3 X Np- = 6 2 X Cp- = 12 e
Ta carbene = 4 CH3 2 X CH3- = 4 e
Ta(V) d0 = 0 Zr Zr(IV) d4 = 0 e
CH3
Total = 10 e Total = 16 e
Bulky Ligands: Sterically demanding ligands will often result in lower than expected electron
counts.
t-Bu t-Bu
t-Bu P Pd P
t-Bu
t-Bu t-Bu
> 18 electron complexes: Complexes with formally 19 or 20 electrons are known, but they are
usually unstable, or adopt alternate configurations.
-e
Co Co Ni Ni
E˚ = -.94 V
vs SCE
18 e 19 e 20 e 18 e
Formal Oxidation State and d electron configuration
Oxidation states in organometallic complexes are merely formalisms that may bear little resemblance to
the actual positive charge on the metal.
"Formalisms are convenient fictions which contain a piece of the truth--and it is so sad
that people spend a lot of time arguing about the deductions they draw, often ingeniously
and artfully, from formalisms, without worrying about their underlying assumptions."
(Roald Hoffman, JACS, 1984, 106, 2006)
Consider the range of possible formal charges on metal centers:

[Fe(CO)4]2- (Collman's reagent): Fe(-II), although the metal likely has little if any negative charge
[ReH9]2-: Re(VII), although it is made by reduction of ReO4- (also Re(VII)) with sodium in ethanol
Therefore, formal oxidations and reductions do not necessarily result in a decrease or increase in electron
density at the metal center. Conversely, reactions where the oxidation state does not change can greatly
affect the electron density of the metal center.
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H+
Fe(CO)42- HFe(CO)4- Oxidation by protonation
Fe(-II), d10 Fe(0), d8
18 e 18 e
H H H 2 H2 = 4 e
2 H- = 4 e
Cy3P H H+ Cy3P H
Ir Ir 2 PCy3 = 4 e
Ir(III) d6 = 6 e Reduction by protonation
H PCy3 H PCy3
H H Total = 18 e
H H
Ir(V), d4
18 e
For π-coordinated ligands (i.e., alkenes, dienes, etc.) a number of different formal oxidation states can be
determined. In the butadiene complex below, the ligand can either be considered an L2 ligand donating 4
electrons, an LX2 donating 6 electrons, or an X4 ligand donating 8 electrons. Therefore, the iron center
can be Fe(0), Fe(II), or Fe(IV). In each case the complex has 18 electrons. These forms can be
considered a type of resonance. All that is changing is where the electrons are formally being assigned.
Fe Fe Fe
OC CO OC CO OC CO
CO CO CO
Fe(0), d8 Fe(II), d6 Fe(IV), d4
Coordination geometry:
Metal coordination geometries can often be predicted based on the number of ligands and VSEPR
theory. Metals with d electron counts resulting in unfilled, half-filled, or fully filled d orbitals will always
follow the VSEPR rules. Metals with d8 electron counts tend to favor lower symmetry structures as we'll
discuss later.
Coordination Geometry Preferred dn Example

Number
2 Linear Ph3P Au Cl
Pt-Bu3
3 T-Shaped d8
Ph Pd
Br
PPh3
3 Trigonal d0, d5, d10
Pd
Ph3P PPh3
PPh3
4 Tetrahedral d0, d5, d10
Pd
PPh3
Ph3P PPh3
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PPh3
4 Square Planar d8
H3C Pd Cl
PPh3
CO
5 Trigonal Bipyramidyl d8, d6 (distorted) CO
OC Fe
CO
CO
5 Square Pyramidal O
O O
V
O O
CO
6 Octahedral d 0, d 3, d 5, d 6 OC CO
Mo
OC CO
CO
Me3P PMe3
8 Dodecahedral d1 H H
Mo
H
H PMe3
Me3P
2-
H H
9 Tricapped Trigonal d0 H
H
Prism H Re
H
H HH
To explain the bonding of ligands to metals, we have to consider the molecular orbitals involved metal-
ligand bonding. Before the development of molecular orbital theory, the interaction of ligands with metals
was described using crystal field theory. We'll discuss this briefly and then consider the true orbital
interactions.
Crystal Field Theory
Assumption: Ligands act as points of negative charge surrounding the metal center
For an isolated metal ion, the 5 d orbitals are degenerate. As an octahedral set of ligands approach, the
d orbitals pointing along the x, y, and z axes (𝑑" # , 𝑑$ #%& # ) are destabilized. The other orbitals (dxy, dyz,
and dxz) are less destabilized.
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eg dz2 dx2-y2
t2g dxy dxz dyz

eg
t2g
ML6n+
Mn+
eg orbitals (ds) can form s bonds with the ligands

t2g orbitals (dp) can form π bonds with the ligands
Crystal field splitting of other common geometries:
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Square
Tetrahedral Planar
d x2-y2
d z2
d xy d yz d xz
d xy
d z2 d x2-y2
d xz d xz
dxy, dyz, dxz dx2-y2
Δ dz2
dxy
dx2-y2 and dz2 dyz and dxz

Tetrahedral Square Planar
High spin and Low spin complexes
Co(III) has the electron configuration [Ar]4s23d4 as a free atom. Upon coordination, the 3d orbitals are
stabilized relative to the 4s and the metal takes on a [Ar]3d64s0 electronic configuration. This
configuration is usually shortened to d6.
A d6 electronic configuration would be expected to strongly favor an octahedral ligand arrangement, since
this would result in the a completely filled set of the low-lying dπ (t2g) orbitals. This electronic configuration
is called the low-spin form, since all electron spins are paired.
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If D is small enough, though, a high-spin form with a t2g4eg2 configuration is possible. In this configuration
there are 4 unpaired electrons.
eg
eg
Δ
Δ
t2g t2g
Low-spin High-spin
The size of the ligand field splitting (D) is dependent on the ligands as well as the metal center.
– 2nd and 3rd row transition metals tend to have higher D
– Higher oxidation state metals have higher D
– π-acceptor and strong s-donor ligands give high D, while π-donor ligands give low D
I- < Br - < Cl- < F- < H2O < NH 3 < PPh 3 < CO, H < SnCl3-
π-donor π-acceptor/
strong σ-donor
Increasing Δ
Ligand Field Theory
Crystal Field Theory is qualitative. To get a better understanding we can turn to a MO picture of bonding
in coordination complexes.
For an octahedral complex of pure s donor ligands, the s, three p, and five d orbitals of the metal interact
with the lone pair orbitals of the ligand.
– 6 of the metal orbitals (s, three p, and 2 ds) are of the appropriate symmetry to interact with the ligand
orbital set.
– Therefore, a set of 6 bonding M-L s MO’s and 6 anti-bonding M-L s * MO’s are formed. The three dπ do
not find a symmetry match and remain as non-bonding orbitals.
– As a result, an octahedral complex can accommodate 18 electrons in the bonding and non-bonding
orbitals. We will see that this maximum is similar to the octet rule in the first row elements.
An octahedral d6 metal complex will have 18 valence electrons. The 6 ligands will each contribute 2
electrons (12 total) and the metal will contribute 6. These 18 electrons will fill all of the bonding orbitals (6
bonds) plus the three non-bonding dπ orbitals (assuming a low spin complex). Note that in a high-spin
complex the filled e2g orbitals are actually M-L antibonding orbitals.
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M-L σ* Deg
eg
t2g
dπ
Mn+
Deg
6 ligand
lone pairs
M-L σ
ML6n+
Types of Ligands
s-donors: Typical M-L bonding arrangement. Lone pair orbital of ligand interacts with metal orbitals.
s-acceptors: M-Z bonding arrangement with the metal as electron pair donor to an empty ligand orbital.
π-acceptors:
Ligands such as CO have empty MO’s of proper symmetry to overlap with the filled dπ orbitals of the
metal center. CO is an example of a π-acceptor ligand (often called a π-acid). In the case of CO, the π*
MO of CO is the orbital that interacts with the metal dπ.
In the MO description above, the CO π* orbitals will interact with the Mdπ orbitals. This interaction
stabilizes the filled Mdπ orbitals. As a result of this bonding interaction, the metal is donating electron
density back to the ligands in a process called back bonding.
– π acceptors form very strong M-L bonds due to this back bonding
– π-acceptors increase the ligand splitting by stabilizing the t2g set of orbitals increasing D
- back bonding allows electron density to be donated back to the ligand. This allows low-valent metals
with filled d orbitals to form complexes with ligands
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M-L π
dπ
π*
M C O
M-L σ
Other π-acceptor ligands: NO, N2, CN-R, PF3
π*
Δ
Δ
dπ
π-donors:
Ligands with lone pairs on the coordinating atom (i.e., -OR, -X, -NR2) can act as π-donor ligands. The
atom can rehybridize to place the lone pairs in orbitals with π symmetry that can overlap with the metal dπ
orbitals.
As a result, the number of electrons that can be donated by these ligands will depend on how electron
deficient the metal is. For example, oxygen could donate 2, 4, or 6 electrons. This concept will be further
developed in the next chapter of notes.
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M-L π
dπ p
M O R
M-L σ
For a metal with filled dπ orbitals, π-donation will result in a destabilization of these orbitals due to
repulsion between the lone pair electrons and the dπ electrons. This results in a smaller D and a weaker
M-L bond.
Δ
Δ
dπ
Ligand
lone pairs
For d0 metals, such as W6+, π-donation is a favorable interaction and leads to stronger M-L bonds.
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π-complexes:
Unsaturated molecules can donate π electrons to form M-L bonds rather than non-bonding lone pairs.
Ethylene is a classic example.
M-L π
π*
dπ
H H
H H
Cl
C
Cl Pt
M π
Cl
H H C
Zeise's Salt--1825
Organometallics, 2001, 20, 2-6
H H
M-L σ
The π orbital of ethylene acts as a s donor. The π* orbital of ethylene is of the proper symmetry to act as
a π-acceptor (back bonding). As a result, the bonding picture is very similar to that of CO. The π-
accepting alkene will lower the energy of the dπ orbitals, resulting in a larger ∆ splitting. As a result, the
complexes will typically be low spin.
Any compound with a π bond can potentially form a π complex with a metal center (alkynes, arenes,
ketones, etc.)
s-complexes:
Dihydrogen can bind to metal centers as an intact molecule. H2 has neither lone pairs nor π electrons.
The electron pair that interacts with the metal center is the s-bonding electrons of the H-H bond. The s*-
orbital can act as a π-acceptor allowing back bonding to occur in the same way as for π-complexes or CO.
M-L π
dπ
σ∗
H
M σ
M-L σ
Other s-complexes that have been identified include: C-H, Si-H, Sn-H, P-H, S-H, B-H, M-H
Kevin Shaughnessy
1. Structure and Bonding 21
2: Survey of Ligand Types--Part 1 (L-type ligands)
A. Neutral s-donor/π acceptors: CO, phosphines, and carbenes
1. Carbonyls
Bonding:
dπ
π*
M C O
M-L σ
s-Donor: The HOMO of CO is a non-bonding lone pair on the C. CO is a strong s-donor.
π-Acceptor: The LUMO of CO is polarized towards the C, as well. This orbital overlaps with the dπ
orbitals of the metal.
Depending on the metal and other ligands, the nature of the CO ligand in LnM-CO can vary.
- If L are good π acids or the complex is cationic, then s-donation will be more important while the
metal will be a weaker π-base. (A)
- If the L are s-donors or the complex is anionic, then the metal will be a strong π-donor. (C)
∂+
M C O M C O M C O
A B C
The degree of back bonding can readily be determined by IR spectroscopy.
V(CO)6 Cr(CO)6 Mn2(CO)10 Fe(CO)5 Co2(CO)8 Ni(CO)4

1976 cm-1 2000 cm-1 2013 cm-1 2023 cm-1 2044 cm-1 2057 cm-1
[Ti(CO)6]2- [V(CO)6]- Cr(CO)6 [Mn(CO)6]+ [Fe(CO)6]2+ CO

1747 cm-1 1860 cm-1 2000 cm-1 2090 cm-1 2204 cm-1 2143 cm-1
Bridging CO: CO is able to bridge 2 or more metals in a variety of ways. Type II CO is a 1 e donor to
each metal. Type III would donate 2/3 e to each metal. In type IV-VI complexes, the CO is an 2e
donor to one metal and a 2e donor to the second metal via a second pair of electrons.
22
O
O
C O O O M
C C C C
M CO M M M M M M
M M
M M
Type I Type II Type III Type IV Type V Type VI
Bridging carbonyls tend to have lower stretching frequencies. Type II = 1850 1700 cm-1; Type III =
1675 - 1600 cm-1.
Type II bridging carbonyls are not metalloketones. The M-C-M angle is between 77 - 90 ˚. The
bonding is delocalized and involves the s and π* MOs of CO.
O O
C C
M M M M
Other unsaturated molecules capable of binding in a similar fashion: CS, CN-R, electrophilic
carbenes, N2, linear NO (+NO)
2. Phosphines
Phosphines are probably the most important organometallic ligands because their steric and
electronic properties can be easily modified.
Bonding: Phosphines, like amines, are strong s-donors. Unlike amines, they are also π-acceptors.
Phosphines are softer Lewis bases than amines, so they tend to coordinate strongly to softer Lewis
acids, such as the later transition metals.
π acceptor ability
PR3 » P(NR2)3 < PAr3 < P(OR)3 < P(OAr)3 < PCl3 < CO » PF3
For PR3, the s* orbital of the P-R interacts with the P d orbital to give a π-acceptor orbital. (Chem.
Commun. 1985, 1810; Inorg. Chem., 1992, 31, 4391)
Kevin Shaughnessy
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Pd PR3 σ* P π acceptor MO M-P backbonding interaction
Phosphines tend to be sterically demanding, and thus steric effects dominate coordination
- Bulky phosphines will tend to bind trans to one another
- The presence of several bulky phosphines will result in deviations from ideal geometries.
Steric and electronic parameters have been developed to account for variations in ligand structure on
the reactivity of metal complexes. Chadwick Tollman, working at DuPont, developed electronic and
steric parameters for phosphines to explain ligand effects on the L4Ni-catalyzed hydrocyanation of
butadiene.
NiL4
+ HCN NC
CN
The steric parameter--q--The Cone Angle:
Tolman developed the cone angle to describe the steric demand of a phosphine ligand. (Tolman,
Chem. Rev., 1977, 77, 313, Adv. Organomet. Chem., 1994, 36, 95-158). Tolman made his
measurements using space filling models (CPK) of the ligands with a fixed M-P bond length (2.28 Å).
In cases where the ligand could have more than one conformation, he chose the conformation giving
the smallest cone angle.
R
R
R
P
2.28Å
M θ
Solid cone angles: The solid cone angle imagines that the metal is a light source. The shadow
projected by the ligands on a sphere at an arbitrary radius (outside the ligands) is then determined.
The challenge is to deal with the numerous areas of overlapping shadows. The are of the sphere that
is in shadow is then mathematically converted to an "cone angle". This method can deal more
effectively with non-symmetrical ligands than Tolman's original method. The STERIC program
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provides a method to calculate cone angles from these computed structures (Taverner, J. Comput.
Chem., 1996, 17, 1612-1623).
Exact Cone Angle: Wesley Allen has developed an approach that uses high level theory to determine
the optimal structure of a metal complex. He then uses this geometry to generate a cone angle using
the Tolman definition rather than a solid cone angle. He calls this method the exact cone angle (J.
Comput. Chem., 2013, 34, 1189-1197).
X-ray cone angles: Cone angles can also be obtained from solid-state structures using any of these
computational methods. These values show true solid state structure, but the solid state structure
may not match the solution structure. (Mingos, Transition Met. Chem., 1995, 20, 533-539)
Percent buried volume: The cone angle concept works well for symmetrical phosphine ligands, but is
less useful for other ligand types, such as non-symmetrical phosphines, N-heterocyclic carbenes, or
chelating ligands. An alternate approach is the percent buried volume (%Vbur), which uses X-ray
structures to determine how much of a hypothetical metal sphere is buried by the ligands. The larger
the %Vbur, the more sterically hindered the ligand. (Cavallo, Organometallics, 2016, 35, 2286). A
simple online tool (SambVca 2.0) can be used to calculate %Vbur from structural data (X-ray or
calculated structures). https://www.molnac.unisa.it/OMtools/sambvca2.0/index.html
Steric parameters for palladium complexes of different ligands
Method P(OMe)3 PMe3 PPh3 PCy3 Pt-Bu3 P(o-tol)3

Tolman 107 118 145 170 182 194
Solid Cone 124 172 194 214
Angle
Exact Cone 120 170 188 176
Angle
Cone Angle 111 148 160
(X-ray)
%Vbur 22% 39% 32% 27% 41%
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The electronic parameter--χ
The electron donating or withdrawing ability of phosphines can be correlated with the CO stretching
frequency of monophosphine metal carbonyls. While any metal carbonyl can be used, LNi(CO)3 is
used most commonly. (J. Organomet. Chem., 1984, 272, 29-41).
L P(t-Bu)3 PMe3 PPh3 P(p-C6H5F)3 P(OMe)3 PF3
CO ν (cm-1) 2056.1 2064.1 2068.9 2071.3 2079.5 2110.8
χ (cm-1) 0.0 8.0 12.8 15.2 23.2 54.7
It had been shown that ligand dissociation from L4Ni was the key step in the hydrocyanation process.
Therefore, Tollman compared his steric and electronic parameters with the KD of the following
reaction.
KD
NiL4 NiL3 + L
The steric parameter gave a good correlation with the dissociation rate of NL4 complexes. It also
correlated with catalyst activity for hydrocyanation of alkenes.
Ligand q KD (M)
P(OEt)3 109 <10-10
PMe3 118 <10-9
P(O-p-C6H4Cl)3 128 2 X 10-10
P(O-p-C6H4CH3)3 128 6 X 10-10
P(O-iPr)3 130 2.7 X 10-5
PEt3 132 1.2 X 10-2
PMePh2 136 5 X 10-2
PPh3 145 No NiL4 detected
It was found that the electronic parameter did not correlate well with kd of NiL4, or with the
hydrocyanation reaction that Tollman was studying.
Chelating phosphines
Chelating phosphines are widely used to control structure and reactivity. Chelating diphosphines
preferentially coordinate in cis fashion, while 2 monophosphines would adopt a trans geometry.
Natural Ligand Bite Angle (bn): The ligand preferred P-M-P angle for a chelating diphosphine. This
can be determined from x-ray structures or by molecular modeling. (Chem. Rev., 2000, 100, 2741-
2769)
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PPh2
PPh2
Me2P PMe2 Ph2P PPh2 PPh2 PPh2

dmpe diphos dppp BINAP
72 ˚ dppe 91 ˚ 92 ˚
85 ˚
PPh2 PPh2
PPh2 O PPh2
Fe
S PPh2
PPh2
dppf Thixantphos NORPHOS
96 ˚ 110 ˚ 123 ˚
3. Carbenes
There are two limiting classes of carbenes: electrophilic (Fischer) carbenes and nucleophilic (Schrock)
carbenes.
R R
M M
R R
Electrophilic (Fischer) carbene Nucleophilic (Schrock) carbene
Fischer carbenes
• Low oxidation state, late transition metals
• π-acceptor ligands on M
• π-donor substituents (R) on the carbene
Fischer carbenes can be considered as neutral 2 e ligands (L-type) derived from singlet carbenes.
Since the carbene is acting as a s-donor, it has a ∂+ charge and acts as an electrophilic center.
Schrock carbenes
• High oxidation state, early transition metals
• non-π-acceptor ligands on M
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• non-π-donor substituents (R) on the carbene
Schrock carbenes are formally considered as X2-type ligands derived from triplet carbenes.
The carbene carbon has a partial negative charge and acts as a nucleophile.
Fischer Carbenes
E. O. Fischer first reported carbene complexes in 1964. (Angew. Chem. Int. Ed., 1964, 3, 580)
Preparation
A. Nucleophilic attack on coordinated ligand
PhLi O O [(CH3)3O]+BF-4- OMe

(OC)5W CO (OC)5W (OC)5W (OC)5W
Ph Ph Ph
LDA O O [Et3O]+BF-4- OEt

(OC)5Cr CO (OC)5Cr (OC)5Cr (OC)5Cr
Ni-Pr2 Ni-Pr2 Ni-Pr2
B. From acetylides (Chugaev, J. Russ. Chem. Soc., 1915, 47, 776; Inorg. Chem. , 1971, 10, 1711)
Cp Cp Cp
H+ MeOH OMe
Fe Fe Fe
OC OC C OC
R R R
PPh3 PPh3 PPh3
C. From stable carbenes (Angew. Chem. Int. Ed. 1997, 36, 2162-2187; J. Organomet. Chem.,
2000, 600, 12-22)
Stable carbenes developed by Arduengo (Acc. Chem. Res. 1999, 32, 913) can be used as neutral 2
e ligands in place of CO or phosphines. The carbene can either be preformed or prepared in situ.
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H
NaH R N
R N N R
N R + H2 + NaCl
Cl-
Mes N Mes Mes Mes

N Mes Mes N N Mes
N N N
Pd(Po-tol3)2 Pd P(o-tol)3 Pd
-P(o-tol)3 N - P(o-tol)3 N N
Mes = mesitylene Mes Mes Mes
Et R
O Cl
N (COD)Rh Mes
(COD)Rh Rh(COD) H 2 N
N Cl- -EtOH
O N
Et R Mes
Unlike the Fischer-type carbenes, imidazolylidenes (N-heterocyclic carbenes, NHCs) tend be strong
sigma donors, but weak π-acids. Originally it was thought that backbonding played little or no role in
the bonding of NHCs to metals. More recent analysis show that backbonding does contribute to the
M-L bond. Nolan determined that backbonding accounted for 13% of the bonding in Pt-NHC
complexes (Orgnaometallics, 2007, 26, 5880).
Schrock Carbenes
Synthesis
The first nucleophilic carbenes were prepared by Schrock in an effort to prepare a homoleptic
tantalum(V) alkyl. (Acc. Chem. Res., 1979, 12, 98)
Np2Zn NpLi t-Bu

TaCl3 Np3TaCl2 [Np5Ta] Np3Ta + Me4C
NpM = M t-Bu t-Bu
Np3Ta H
t-Bu
Sterically crowded early transition metal alkyls undergo a-elimination readily to give nucleophilic
carbenes and alkanes. Carbene formation can be promoted by increasing the steric strain in a metal
complex.
CpTl
Np2TaCl3 + CMe4
Ta
Cl t-Bu
Cl
Structure
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Schrock carbenes tend to have strong a-agostic interactions that result in significant distortions from
idealized bond angles. In some cases, the carbene complex will be in equilibrium with a tautomeric
carbyne-hydride.
84.8 ˚
H
113.7˚
(Me3P)Cl3Ta
t-Bu
161/2˚
H H
(dmpe)2Ta (dmpe)2Ta t-Bu
t-Bu
J. Am. Chem. Soc., 1982, 104, 1710
Carbynes and Carbides
Compounds with formal metal-carbon triple bonds are also known. Like carbenes, electrophilic (Fischer)
and nucleophilic (Schrock) extremes can be envisioned for the bonding model. The electrophilic carbyne
complex is derived from a doublet carbine (4e LX-type ligand), while the nucleophilic complex is derived
from a quartet carbine (6e X3-type ligand). The distinction between Fischer and Schrock carbynes is not
nearly as distinct as in the case of carbenes.
R M R M
Electrophilic (Fischer) carbyne Nucleophilic (Schrock) carbyne
Synthesis of Fischer carbynes:
Fisher carbynes can be made by Lewis acid abstraction of alkoxide from alkoxy carbene complexes.
OMe BBr3
(OC)5Cr Br(OC)4Cr CH3 + BBr2OMe
CH3
Synthesis of Schrock carbynes
Schrock carbynes can be prepared by deprotonation or a-elimination of Schrock carbenes.
1) PMe3
2) Ph3PCH2
Cl Ta H Cl Ta
+ Ph3PCH3 Cl
Cl Me3P t-Bu
t-Bu
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Group VI complexes of tetradentate nitrogen ligands undergo double dehydrogenation to give carbynes
starting from metal alkyl complexes.
H 3C H
H 3C
XC6F 5 CH2 C F C H
C6F 5 C6F 5 6 5 C6F 5 C6F 5
N CH 3CH2Li
N W C6F 5 N W N C6F 5 N W N C6F 5
N N N
N N N
CH 3
C C6F 5
-H2 C6F 5
N W N C6F 5
N Schrock, et al, Organometallics, 1998, 17 , 1058.
N
Like alkynes, terminal carbynes can be deprotonated. For example, Cummins showed that the Mo
carbyne complex below could be deprotonated with benzyl potassium. The initial product is a dimer with
the potassium ions bridging two carbide anions. Treatment with cryptands or crown ethers gave the free
carbide complex. (Chem. Commun., 1997, 1995-1996)
CH C
t-Bu 1) KCH2Ph t-Bu K+(Bz-15-c-5)2
t-Bu Mo N t-Bu Mo N
N t-Bu N t-Bu
N Ar 2) benzo-15-c-5 N Ar
Ar Ar
Ar Ar
B. π-electron donor ligands
1. alkenes, alkynes, polyenes, and arenes
A. Alkene complexes: π-bonds can act as s-donor/π-acceptor ligands similar to CO.
As the metal becomes more π-basic, the π* orbital of the ligand becomes more populated.
Therefore, the unsaturated C-C bond is weakened.
Increasing
back bonding
M M
L-Type X2-type
H H H
H
Cl Ph3P
Cl Pt 1.37 Å Pt 1.43 Å
Cl Ph3P
H
H H
H
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Factors favoring X2-type binding

- strong donor ligands
- a net negative charge on the complex
- low-oxidation state metals
Reactivity difference between the bonding types:

L-type: the alkene is electron deficient and prone to attack by nucleophiles
X2-type: the carbons are carbanion-like and prone to attack by electrophiles
Olefin binding strengths:
- Olefin coordination is very sensitive to steric changes: ethylene > propylene > cis-2-butene >
trans-2-butene
- Chelating dienes form more stable complexes than simple alkenes.
Cl
Cl
Pd Rh Rh
Cl Cl
(η4-cyclooctadiene)palladium dichloride (η4-norbornadiene)rhodium(I) chloride dimer

(COD)PdCl2 [(nbd)RhCl]2
- Due to the shift to sp3 hybridization upon binding, strained olefins bind more strongly than
unstrained ones
Cr(CO)5 + Cr(CO)5 +
(coe)
B. Alkyne complexes: Alkynes can bind to metal centers in the same way as alkenes
Alkynes are more electronegative, therefore are better π-acceptors
30 - 40 ˚
R R R R
M M
Metals can stabilize alkynes that cannot be observed as free compounds
1) MeLi
2) heat
Cp2Zr Cp2Zr + CH4
Cl
Chem. Rev., 1988, 88, 1047-1058
Alkynes can bridge M-M bonds. The alkyne acts as a 2e donor to each metal center
Kevin Shaughnessy
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Ph
Ph Ph
Ph
(OC)3Co Co(CO)3 (OC)3Co Co(CO)3
C. h4-Diene Complexes: 1,3-Dienes can act as L2-type (4 e) or LX2-type (6 e) ligands
1.46 Å 1.46 Å
PMe3
1.46 Å 1.46 Å H H Cl
H H Hf
H H
H H M
Fe M Cl
OC CO 1.40 Å
CO PMe3
J. Chem. Soc., Dalton, 1992,
2641
Although cis-diene coordination is much more common, trans-diene coordination is observed

occasionally. (J. Am. Chem. Soc., 1980, 102, 6344)
Cp2 Cp2
Zr Zr Thermodynamic: 1:1 cis:trans
Photochemical: all trans
D. Arene complexes: Arenes usually will bind h6-fashion, but h4- and h2-complexes are known in
cases where h6-coordination would exceed 18 electrons at the metal
CH3
H3C CH3
2+
CH3
H3C RuCH3
Cr H3N NH3
Ru Os
Ph3P Cl H3N NH3
Cl NH3
η6-arene η4-arene η2-arene
Prof. Dean Harman (UVa) has developed very rich chemistry based on the h2-coordination of
Os(NH3)52+ to arenes. (Chem. Rev., 1997, 97, 1953-1978)
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Crystal structure of (h2-naphthalene)Os(NH3)52+: Organometallics, 1997, 16, 3672-3678
2. s-Complexes: Dihydrogen, Silanes, Boranes, Alkanes, etc. (Review: Crabtree, Angew. Chem.
Int. Ed., 1993, 32, 789)
A. Dihydrogen complexes: First reported in 1984 by Kubas (JACS, 1984, 96, 480)
L CO
H2 H
(i-Pr3P)2W(CO)3 OC W
H
OC L
Transient dihydrogen complexes are believed to be intermediates in the oxidative addition of H2 to

give metal dihydride complexes.
B. Alkane complexes:
1. Agostic C-H complexes: Coordination of a C-H bond that is present in a bound ligand.
(Original description: Brookhart and Green, J. Organomet. Chem., 1983, 350, 395-408)
PPh3
Me2 Cl H2 Ph3P
Ru
Cl
P C CH2 Ar N N Ar
Ti Cl PPh2
H H Pd
P
Me2 Cl Cl H
2.59Å
-8.0 ppm
Characterization of agostic complexes
Crystallography: Characterized by close M-H contacts. C-H bonds are lengthened. M-H
distance is longer than for a metal-hydride
NMR: Both 1H and 13C appear upfield compared to normal alkyl chemical shifts. J(13C-1H) is
typically lower than for a non-bridged species (75 - 120 Hz vs. 100 - 150 Hz). Agostic
interactions are often fluxional.
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IR: Lower C-H stretching frequencies are sometimes observed (2700 - 2350 cm-1)
Agostic interactions are often fluctional, so they can be hard to observe.
Agostic interactions help to stabilize metal alkyls. They also can be considered as "stable
intermediates" of migratory insertion/ß-hydride elimination. Agostic complexes play important
roles in olefin polymerization catalysts.
2. Alkane complexes: Alkanes can act as ligands to metal centers, but bind very weakly. Direct
observation of alkane complexes is difficult. Alkane complexes are thought to be key
intermediates in oxidative addition/reductive elimination of alkanes. Review: Young, Chem—Eur.
J. 2014, 20, 12704-12718
Alkane bonding modes:
H H H H H
H M M
M H C M C H C H C C H
H H H M
H H H H H H
κ1 -H κ2-H,H κ3-H,H,H κ2-H,C agostic
Observation by time resolved IR: Many examples of 16 e metal carbonyls coordinating to

alkanes have been observed, although lifetimes of these complexes are very short (300 ns -
200 µs)
hν 266 nm
CpRe(CO) 3 CpRe(CO)2(heptane) + CO CpRe(CO) 3 + heptane
heptane k = 2.1 X 10 3 l/mol s
IR: 2032, 1940 IR:1951, 1866
JACS, 1997, 119 , 7521-7525; JACS, 2012, 133 , 2303
Kevin Shaughnessy
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Observation by NMR: JACS, 1998, 120, 9953-9954; Chem. Commun. 2009, 1401-1403
hν
CpRe(CO) 3 1H NMR: ∂ 4.92, ∂ -2.32 (5:2)
H
1H NMR: ∂5.32
cyclopentane OC Re 1J
CH = 112.9 Hz
1J
CH = 129.4 Hz OC H
A methane adduct of a Rh(I) pincer complex has been characterized by NMR. The methane ligand is
fluxional at -110 °C, so that all 4 H's are equivalent. Science, 2009, 326, 553-556
O Pt-Bu2 O Pt-Bu2
13 CH HB(C 6F 5)3•OEt2 H
N Rh 3 N Rh 13 C NMR: -41.7 ppm (pentet)
CDCl2F, -110 °C 13 CH
3 1J = 124 Hz
C-H
O Pt-Bu2 O Pt-Bu2 (free CH 4 = 125 Hz)
Crystallographic characterization: Alkane complexes are generally not stable enough to be characterized
crystallographically. The first example of an unambiguous examples of an alkane complex was reported
by Macgregor. (Science, 2012, 337, 1648-1651). To avoid loss of the alkane, the alkane complex was
generated by reduction of a coordinated norbornadiene ligand in a single crystal, solid-state reaction.
+ + +
R2 R2 R2
P H2 P H2 H
Rh Rh P
P Rh H
P solid state solid state P
R2 R2 H H R2 H
R = i-Bu H
Rh1-C1, 2.214(13) Å; Rh1-C2, 2.169(12) Å
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Macgregor has extended this to a linear alkane complex by solid-state reduction of a Rh 1,3-pentadiene
complex to a Rh pentane complex with a chelating interaction with the two methylene units. Angew.
Chem. Int. Ed. 2016, 55, 3677
+ +
R2 R2 H
P H2 P H
Rh Rh H
P solid state P
R2 R2 H
R = cyclohexyl
2. Silanes and boranes
PEt2
Et2P CO
PhSiH3 Mo H
Mo(CO)(Et2PC2H4PEt2)2 Et2P
PEt2 Si
JACS, 1995, 117, 10312 Ph
H
H
-5.5 ppm
broad
O O
H O H O
B PhSiH3 B O
Cp Cp + HB
Ti Ti
Cp Cp H O
B
O
H O H Si
H Ph
JACS, 1999, 121, 5033-5046
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2: Survey of Ligand Types--Part 2 (X-type ligands)
1. Hydrides
History
1931: H2Fe(CO)4 prepared by Hieber, although the hydride structure was not accepted initially
1955-1964: Cp2ReH, (PR3)2PtHCl, and K2[ReH9] prepared showing that M-H bonds do exist
1984: Dihydrogen complexes discovered (M-H2)
Bond strength
M-H BDE energies are typically between 60 and 70 kJ/mol. M-H bond strengths increase moving
down columns (1st row < 2nd row < 3rd row)
Structure of hydride complexes:
Terminal Hydrides
Hydrides are stereochemically active: the hydride generally occupies a normal coordination site in
the complex. Due to its small size, the complex's geometry can be perturbed if there are other large
ligands present.
95 ˚
CO
OC CO
Mn
OC CO
H
1.5 Å
Inorg. Chem. 1969, 8, 1928
PPh3
104.6 ˚
Rh
PPh3
Ph3P
H PPh3 113.4 ˚
Inorg. Chim. Acta., 1989, 166 , 173
Organometallics, 1996, 15, 1721
Bridging Hydrides
Bridging hydrides always adopt a bent M-H-M conformation. The bonding is similar to the 3 center/2
electron bonding B-H-B bridge in boranes.
The bonding can be thought of as a s-bond complex of an M-H bond to the other metal center.
Thus, there would be two resonance structures for a bridging hydride. Often this is drawn showing a
M-M bond as well as the M-H bonds.
Kevin Shaughnessy
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H H H
M M' M M' = M M'
In the ionic model, the hydride is a 1 electron donor to each metal. The M-M' bond donates 1
electron to each metal as well.
Synthesis of metal hydrides:
1) Protonation
-Mn(CO) CF3SO3H
5 HMn(CO)5
THF
HClO4
Os(CO)3(PPh3)2 [HOs(CO)3(PPh3)2]+ ClO4-
2) Hydride donors
Cp2ZrCl2 HAl(i-Bu)2
Cp2ZrHCl
CH3
CH3 H
TaCl5 + LiAlH4 + Ta H
H
3) From H2
CH3
Ph2 H2 (1 atm) Ph2 H
P Cl P Cl
Ir Ir
P CO P H
Ph2 Ph2 CO
4) Elimination
RuCl2(PPh3)3 2 KOi-Pr H2Ru(PPh3)4 + 2 Me2C=O + 2 KCl

PPh3
Cp2ZrCl2 t-BuMgCl Cp2ZrHCl +
Characterization
NMR: Hydrides usually appear very far upfield (0 - -60 ppm). For example:
HCo(CO)4 (-10.7 ppm) HMn(CO)5 (-7.5 ppm) (Cy3P)2Pt(H)OPh (-17.5 ppm)
These upfield shifts do not necessarily imply strong hydridic character. The upfield chemical shift is
largely due to mixing of low-lying excited states with the ground state when the magnetic field is
applied. (J. Chem. Soc. 1964, 2747 and 4583). This tendency is strongest for d1 - d9 metals, while
d0 and d10 metals, which do not have low lying excited states, generally give hydride shifts downfield
of TMS.
Cp2ZrH2 (7.46 ppm) [HCuP(p-tol)3]6 (3.5 ppm)
Kevin Shaughnessy
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IR: Terminal M-H stretching frequency are usually between 1500 - 2200 cm-1. Bridging hydrides
generally have lower energy vibrations (800 - 1600 cm-1). The intensities are usually weak for metal
hydrides. Raman often gives more intense absorptions.
Crystallography: The hydrogenhas little electron density and does not scatter X-rays well, so
hydride ligands can be difficult to find. Since X-rays are scattered by electron density, which is
between the M and H nuclei, M-H bond distances are usually underestimated by 0.1 Å.
Neutrons diffraction detects the hydrogen nucleus, so these experiments tend to give more accurate
M-H distances. Neutron structures usually require very large crystals and synchrotron neutron
sources.
Acidity
Many hydrides are appreciably acidic.
General trends:
- pKa generally increases as you move down a column—stronger M-H bond
- electron donating ligands increase pKa values
Hydride pKa (CH3CN)
HMn(CO)5 14.1
HMn(CO)5PPh3 20.4
HRe(CO)5 21
HFe(CO)2Cp 19.4
HFe(CO)2Cp* 26.3
CpCr(CO)3H 13.3
CpMo(CO)3H 13.9
CpW(CO)3H 16.1
From Hartwig, Organotransition Metal Chemistry, University Science Books, 2010, pg. 129.
• Alkyls, Vinyls, and Aryls
Metal alkyls: stabilized carbanions

- As the metal electronegativity increases, the nucleophilic reactivity of the M-C bond decreases.
- Nucleophilic reactivity decreases with more stable carbanions (i.e. -CH3 < -C6H5 < -CCR).
- M-C bond strength increases moving down columns. M-C BDE typically are weaker than M-H
bonds. Most fall in the range of 30-60 kcal/mol
Early transition metal alkyls are very sensitive to water and oxygen.
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Late transition metal alkyls are more stable to water and oxygen.
Stability of Transition metal alkyls: Originally it was thought that the transition metal-carbon bond
was too weak to give stable products.
Actually lack of kinetic stability rather than thermodynamic stability was the problem
Decomposition pathways:
– ß-hydride elimination:
H2C
H2 H2 CH2
C C LnM LnM-H + CH2=CH2
LnM H H
ß-Hydride elimination occurs for nearly all transition metal-alkyls that meet the following
requirements:
1. The b carbon must have hydrogen substituents

2. The M-C-C-H unit can adopt a roughly syn-coplanar conformation that brings the ß-hydrogen
close to the metal center.
3. There is a vacant coordination site (orbital) cis to the alkyl substituent
Metal-alkyls that are stable to b-hydride elimination
1. Alkyls that do not have b-hydrogens
2. Alkyls for which the ß-hydrogen cannot approach the metal center
3. Alkyls in which the M-C-C-H unit cannot become coplanar
4. 18-electron species that cannot dissociate a ligand
5. Some d0- alkyls
– a-hydride elimination:
For early transition metal alkyls, a-hydride elimination can be an important decomposition
pathway.
Kevin Shaughnessy
41
L2Cl2Ta L2Cl2Ta
Zn 2 Li
TaCl5 Ta(Np)3Cl2 + (CH3)4C
Np2Zn Np3Ta
J. Am. Chem. Soc. 1978, 100, 3359
– Reductive Elimination:
R reductive
LnM elimination LnM + R-H
H 16 e
18 e M(N-2)
M(N)
Kevin Shaughnessy
42
Synthesis of Transition Metal Alkyls
1) Alkylation with a nucleophilic organometallic species
MgCl
ZrCl4
ZrBz4
2) Nucleophilic addition to an electrophilic alkyl
CH 3CH2I Fe CH2
Fe + I-
OC OC CH 3
CO CO
3) Oxidative Addition
CH 3
Cl PPh 3 CH 3I Cl PPh 3
Ir Ir
Ph 3P CO Ph 3P CO
I
4) Insertion
H
Zr Zr
Cl Cl
3. LnX carbon ligands
A. π-Allyl complexes: The allyl group (C3H6-) can act as an h1-X or h3-LX ligand.
CO CO
OC CO heat or hν
Mn OC
Mn + CO
OC OC
CO CO
η1-allyl η3-allyl
Kevin Shaughnessy
43
Orbital interactions
Increasing Energy
M M M
pz (s, dz2) dyz (py) dxz (px)
B. Cyclopentadienyl (Cp) complexes
Cp complexes of all transition metals are known. The Cp ligand binds strongly and is resistant to
attacks by nucleophiles and electrophiles, so it makes a good spectator ligand in many cases.
Types of Cp complexes:
L
M M L M
L L L
L
Metallocenes Bent Metallocenes Half-Sandwich
i. Metallocenes
Ferrocene
Fe
Original structure reported:
T. J. Kealy, P. L. Pauson, Nature, 1951,168, 1039
MgCl + FeCl3
X
J. A. Tebboth, J. F. Tremaine, J. Chem. Soc., 1952 , 632-635 (by another route)
Correct structure originally proposed in 1952:

G. Wilkinson, R.B. Woodward, et al, J. Am. Chem. Soc., 1952, 74, 2125-2126
Fe E. O. Fischer, W. Pfab, Z. Naturforsch. B, 1952, 7, 377-379
Crystal structure:
P. F. eilan, R. Pepinsky, J. Am. Chem. Soc., 1952, 74, 4971
L. E. Orgel, J. D. Dumitz, Nature, 1953, 171, 121-122
Kevin Shaughnessy
44
V Cr Mn Fe Fe Co Co Ni
d3 d4 d5 d6 d5 d7 d6 d8
15 e 16 e 17 e 18 e 17 e 19 e 18 e 20 e
MO diagram for metal-Cp bonding
Cp and Cp2 π-molecular orbitals: The Cp molecular orbitals have three energy levels. One that his
fully symmetric, two degenerate orbitals with a single node (p-symmetry), and two degenerate orbitals
with two nodes (d-symmetry). These can be combined to give a set of orbitals for the Cp2
environmental of a metallocene.
Cp MO diagram
Cp2 MO diagram
Combining the Cp2 orbitals with the metal orbitals give the following interactions.
Kevin Shaughnessy
45
e2u
e2g e1u
a2u
a1g
e1g
e2g
a1g
e1g
e1u
a2u
a1g
Kevin Shaughnessy
46
ii. Bent Metallocenes: Metals of group 4 and the 2nd and 3rd rows of groups 5-7 do not form stable
Cp2M complexes. However they do form stable metallocenes with additional ligands attached to the
metal center.
L L
M L M M L
L L
d4, d 2 d0, d1 , d 2 d0
Cl H
Zr Ta H
Mo CO
Cl H
iii. Half-Sandwich Complexes (Piano Stool Complexes): Metallocenes have limited reactivity
because they are typically coordinatively saturated. Bent-metallocenes offer more interesting
chemistry (olefin polymerization), but half-sandwich complexes offer the most diverse reactivity.
Some examples:
OC
OC CO
V Fe Ni Cu Mn Mn
OC CO CO I
Cl OC OC CO
OC CO CO CO CO
iv. Other important Cp-type ligands:
CH3
H3C CH3
Cl Ti Cl
H3C CH3
Indenyl Fluorenyl
Cp*
bis(indenyl)
4. Halides, Alkoxides, Amides, etc.
This class of ligands contain additional lone pairs that can be donated to the same metal (π-donors) or to
another metal center (bridging species).
A. π-donors: amide, alkoxide, and fluoride are strong π-donors.
In late, 18 e transition metal complexes, π donation weakens the M-X bond due to repulsion between
filled orbitals.
Kevin Shaughnessy
47
In early transition metals π-donation is a favorable interaction between the filled ligand orbital and
empty dπ orbitals on the metal center. Early transition metals are often referred to as being oxophilic
or fluorophilic.
Alkoxides: Alkoxides commonly act as bridging ligands for electropositive metals. To avoid formation
of bridges, bulky alkoxides must be used. With high valent transition metals, π-donation becomes
important. M-O-C angles approaching 120 ˚ or even 180 ˚ are common.
t-BuH2C 169 ˚
CH2t-Bu
t-BuH2C
O O O t-Bu
O t-Bu
CH2t-Bu
Ru Ru Mo Mo t-Bu
O Li(OEt2)2
O O O O O O ZrCl3
Me Me 135˚
t-Bu O
J. Am. Chem. Soc, 1989
111, 4712-4718 t-Bu
Inorg. Chem., 1984, 5, 613-618 t-Bu
An angle near 120 ˚ suggests that the O is sp2 hybridized and acting as a 4 electron donor (LX).
An angle near 180 ˚ suggests that the O is sp hybridized and acting as a 6 electron donor (LX2). In
this case the alkoxide can be considered to be isoelectronic with the Cp ligand.
Tp
O
Zr
CH3
CH3 TpO-
CH3 Zr
CH3
O
O
Tp
Dialkylamido ligands (-NR2) often act as 4 electron LX donors to high valent metals. The nitrogen
adopts a planar configuration suggesting sp2 hybridization.
B. Bridging:
Halides other than fluoride, non-bulky alkoxides, thiolates and phosphides have a strong tendency to
act as bridging ligands.
X
M M'
Coordinatively unsaturated metal halides often dimerize to give halide bridged species. These
species can be cleaved by reaction with an additional coordinating ligand.
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48
(o-tol)3P Br (o-tol)3P Br
2 PhNH 2
Pd Pd 2 Pd
Br P(o-tol)3 NH 2Ph
o-tol = 2-methylphenyl (2-tolyl)
Kevin Shaughnessy
49
3-Ligand Substitution
Limiting mechanisms for ligand substitution:
Associative Mechanism (A): Bond making occurs before bond breaking.
Dissociative Mechanism (B): Bond breaking occurs before bond making.
Mechanisms between these two extremes are called Interchange (I) mechanisms. These can be
associatively activated (Ia) or dissociatively activated (Id).
Associative Mechanism: This is the most common mechanism for coordinatively unsaturated metal
complexes. The d8 square planar complexes are prototypical examples. Square planar complexes of
Pt(II), Pd(II), Ir(I), and Rh(I) have been extensively studied.
Y Lc
Lc X Lc X Y
Pt + Y Pt Lt Pt
Lt Lc Lt Lc X
Lc
Lc Y Lc Y
Pt Pt + X
Lt Lc Lt Lc
X
Characteristics of this reaction:
1. Stereochemistry at the metal center is usually retained
2. Kinetics are second order, although the rate law usually has two terms: rate = k1[Pt] + k2[Pt][Y]
3. Negative entropy of activation (DS‡ = -40 to - 60 J/mol•K)
4. The reaction rate is dependent on:
5. the incoming ligand: PR3 > pyridine > NH3, Cl- > H2O > -OH--range = 105
6. the leaving ligand: NO3- > H2O > Cl- > Br- > I- > N3- > CN-
7. the metal: M2+ = Ni > Pd >> Pt--range = 106
8. ligands cis and trans to the leaving ligand
Kinetics of Associative Ligand Substitution:
The simple associative substitution follows a second order rate law: rate = k2[M][Nu]. Kinetics
studies of associative substitution, however, often give more complex rate laws. Ligand substitution
of square planar Pt(II) complexes are a classic example.
Kevin Shaughnessy
50
Br Br -
k2
Et3P Pt NH3 + Br- Et3P Pt Br + NH3
Br Br
Inorg. Chem. 1970, 9, 258-261
Pseudo-first order rate constants (k0bs) were determined at various [Br-] values. A plot of kobs vs. [Br-]
will give the k2 second order rate constant for the reaction. If the reaction followed clean second
order kinetics, the y-intercept would be zero. In fact, the y-intercept is not zero.
kobs
m = k2
y-intercept = k1
[Br-]
The nonzero y-intercept indicates that there is a second process that is not dependent on [Br-].
Rate = (𝑘. + 𝑘0 [Br – ])[(Et 8 P)PtBr0 (NH8 )]
The [Br-] independent term is due to a mechanism where ligand substitution by solvent occurs,
followed by displacement of solvent by the nucleophile in a fast step.
Br
Et3P Pt OH2 k3 (fast)

k1 = 5.8 X 10-5 1/s
Br Br-
H2O
Br Br -
k2 = 2.3 X 10-2 1/M•s
Et3P Pt NH3 Et3P Pt Br
Br-
Br Br
The trans-effect and -influence:

Trans-influence: Extent to which a ligand weakens the bond trans to itself.
Trans-effect: The effect of a ligand upon the rate of ligand replacement of the group trans to itself.
Et3P Cl Et3P py
EtOH Pt
Pt N
Lt PEt3 Cl-
Lt PEt3
Kevin Shaughnessy
51
Lt H CH3 C 6H 5 Cl
Rel. Rate 104 1.7 X 103 400 1
J. Chem. Soc. 1961, 2207.
Trans effect/influence series:
H- , CH3-, olefins, CO > PR3, I- > Br- > Cl- > NH3 > OH- > H2O
Why??:
s-donors: Strong s-donors increase the electron density of the orbital that points towards the
trans ligand
π-acceptors: Strong π acids stabilize the trigonal bipyramidal intermediate (withdraws electron
density away from ligands Y and X in the intermediate.
The trans influence/effect can be used to predict substitution stereochemistry.
2-
Cl NH3
2 eq. NH3
Cl Pt Cl Cl Pt NH3
Cl Cl
2+
NH3 NH3
2eq Cl-
H3N Pt NH3 Cl Pt Cl
NH3 NH3
For a more extensive listing of the trans influence of ligands see, Coord. Chem. Rev. 1973, 10, 335.
Cis influence/effect
Cis ligands also affect substitution rates, but to a much smaller extent.
Et3P py
Et3P Cl EtOH Pt
Pt N
Et3P Lc Cl-
Et3P Lc
Lt CH3 C 6H 5 Cl
Rel. Rate 3.6 2.3 1
J. Chem. Soc. 1961, 2207.
Dissociative Substitution
Dissociative substitution is normally the preferred mechanism for coordinatively saturated 18 e

complexes, since they can more readily form a 16 electron complex than one with 20 electrons. The
Kevin Shaughnessy
52
rates of ligand substitution for coordinatively saturated complexes are usually significantly slower than
those for coordinatively unsaturated complexes.
O O
Rh + Rh + 104/sec
O assoc. O
Rh + Rh + 10-10/sec
dissoc.
CO L
-CO. k1 L
Ni (CO)3Ni(solvent) Ni
CO k2 CO
OC CO +CO, k-1 OC CO
fast
<= <# [>][?@(AB)C ]

6. rate= If k2 >> k-1 then the rate law is simplified to rate = k1[Ni(CO)4]
<D= [AB]E<# [>]
7. DH‡ = 105 kJ/mol, which is close to the Ni-CO BDE
8. DS‡ = 33 J/mol•K
Stereochemistry of Substitution: Both retention and inversion are observed for dissociative ligand
substitutions.
square trigonal distorted

pyramidal bipyramidal trigonal
bipyramidal
L L LL L
L L
L
L' M L L' M L' M L' M
L -L L L L L
L L L
L" L" L"
L L" L
L L L
L' M L" L' M L L' M L
L L L
L L L"
Dissociation of a ligand from an octahedral complex gives a square pyramidal ML5 complex. If L' is a
strong trans effect ligand, this geometry is stable and substitution will occur with retention. For d6
metals, the trigonal bipyramidal structure is not stable and retention is preferred. A distorted trigonal
bipyramid is preferred when L' is a π-donor ligand, which can result in a mixture of stereoisomers.
Kevin Shaughnessy
53
Pseudo-four-coordinate, 18 electron metal complexes can be chiral at the metal center. In many
cases these complexes can be resolved. Racemization of these complexes occurs by a dissociative
mechanism. Loss of phosphine gives a fluxional intermediate. Recoordination of phosphine can give
either enantiomer of the metal complex. Substitution with a large excess of a phosphite gives
substitution with retention of stereochemistry.
25 ˚C, toluene
O O O
Mn Mn Mn
PPh3 t1/2 = 21 min
ON rate ∝ 1/[PPh3] PPh3 Ph3P
ON NO
Ph Ph Ph
-PPh3 PPh3 PPh3
P(OC6H4OMe)3
large excess
O O
Mn Mn
ON NO
Ph Ph
O
Mn
P
ON O OMe
Ph
3
Dependence of Dissociative Substitution on the Metal Center:
Electronic configuration: d8 > d10 >> d6

d6 metals are often referred to as being substitutionally inert.
17 electron complexes:
17 electron complexes undergo ligand dissociation much faster than 18 electron complexes (103 to
107 times faster).
PPh3
V(CO)6 (PPh3)V(CO)5 + CO
-70 °C
90 minutes
molten
PPh3
[V(CO)6]- No reaction
Do 17 electron complexes undergo associative or dissociative ligand substitution?
≤ 25 °C
V(CO)6 + L (PPh3)V(CO)5 + CO
J. Am. Chem. Soc., 1984, 106, 71
Kevin Shaughnessy
54
• rate µ [L]
• rate is unaffected by [CO]
• ∆S‡ = -118 J/mol•K (L = PPh3)
The rate of the reaction was largely unaffected by the size of the incoming ligand. Only P(i-Pr)3
showed a significantly slower rate than less sterically demanding ligands.
Do 18 electron complexes ever undergo ligand substitution by an associative mechanism?
Yes, but usually only when a poly-hapto ligand or chelating ligand can adopt a lower hapticity
coordination. This is necessary to avoid a 20 e intermediate.
Rh + PPh 3 Rh + CO
OC CO Rh OC PPh 3
OC PPh 3
CO
JCS, Chem. Commun. 1983, 1208
Catalyzed or Assisted Ligand Substitution
Electron-Transfer Catalysis:
Odd number (17 or 19 e) species typically undergo ligand substitution at much higher rates than 18 e
complexes. This fact can be used to accelerate ligand substitution reactions.
Catalysis by oxidation:
Oxidation of 18 e electron complexes will give substitutionally labile 17 e complexes. Rapid

ligand substitution follows the oxidation. In many cases these reactions are electrocatalytic. For
this reaction to be catalytic, it is necessary that the oxidation potential of the product be more
positive than that of the starting complex. In the case below the oxidation potential of the starting
complex is 0.22 V (vs. ferrocene/ferrocenium) and the E° of the product is 0.55 V.
Kevin Shaughnessy
55
-e- PPh3
Mn Mn Mn
CO CO CO
H3CCN H3CCN CO -CH3CN Ph3P
CO CO
J. Am. Chem. Soc. 1982, 104, 3034

J. Am. Chem. Soc. 1983, 105, 61
Mn Mn
CO CO
Ph3P H3CCN CO
CO
Catalysis by reduction: Reduction to 19 e species can also accelerate ligand substitution. This is
commonly used for metal carbonyls.
Na+(O-CPh2) -CO PPh3

Fe(CO)5 [Fe(CO)5] [Fe(CO)4] [(PPh3)Fe(CO)4]
(PPh3)Fe(CO)4 Fe(CO)5
Photochemical Ligand Substitution:
Photolysis of metal complexes can lead to ligand dissociation, which will accelerate ligand
substitution.
CO THF
OC CO hν OC CO
W W + CO
OC CO THF OC CO
CO CO
L'
L hν (400 nm) OC CO
Chem. Rev.,1974, 74, 401 L = pyridine W
L' OC CO
CO
L
OC CO
W
OC CO L
CO
OC L'
hν (250 nm) W
L = pyridine OC CO
L' CO
Kevin Shaughnessy
56
Carbonyls: Substitution of substitutionally inert octahedral metal complexes can be accelerated

by UV or in some cases visible light. Absorption of light by an octahedral results in promotion of
an electron from the t2g (dπ) to the eg (ds), which is an anti-bonding M-L orbital.
M-M bonds: Weak M-M bonds can be homolyzed photochemically. Homolysis of Mn2(CO)5
gives the 17 electron Mn(CO)5 species that undergoes rapid substitution. Recombination of the
17 electron species gives Mn2(CO)9PPh3.
hν
(OC)5Mn Mn(CO)5 2 Mn(CO)5
Mn(CO)5 + PPh3 Mn(CO)4PPh3 + CO
Mn(CO)4PPh3 + Mn(CO)5 (OC)5Mn Mn(CO)4PPh3
Nucleophile Assisted Substitution: Oxygen transfer reagents (i.e., R3NO, R3PO, DMSO) can induce
decarbonylation of metal carbonyls by an oxidative mechanism. (Coord. Chem. Rev., 1984, 53, 227-
259)
Fe(CO)5 + Me3NO (NMe3)Fe(CO)4 + CO2
Me3N
O
(OC)4Fe
O
excess Me3NO
2 PPh3
Fe Fe + 2 CO2 + 2 Me3N
CO PPh3
OC CO OC PPh3
J. Organomet. Chem., 1979, 179, C5-C6
Kevin Shaughnessy
57
4-Oxidative Addition/Reductive Elimination
Oxid. Add. A
A
LnMm+ + LnM(m+2)+
B
Red. Elim. B
ne n+2 e
Oxidative Addition: Addition of A-B to a metal center resulting in an increase in coordination number by
two, an increase of oxidation state by 2 units, and an increase in the electron count by 2.
Reductive Elimination: Elimination of two ligands from a metal center to give a new A-B bond. The metal
center is reduced by 2 units and has 2 fewer coordinated ligands. The complex has 2 less electrons.
Oxidative addition and reductive elimination are the microscopic reverse of each other. They represent
the forward and reverse reaction of an equilibrium. The position of the equilibrium depends on the
thermodynamics of the oxidative addition (or reductive elimination process). For example many metal
complexes will oxidatively add CH3I, but few will reductively eliminate this compound. In contrast M(H)R
usually undergo rapid reductive elimination, but oxidative addition of alkanes is much less common.
General features of oxidative addition:
• Oxidative addition favored at more electron-rich metal centers.

• Oxidative addition favored at less sterically demanding metal centers
• Oxidative addition generally requires an electron count of 16 or less (17 electrons for bimolecular
oxidative addition). There must be at least 2 d electrons for oxidative addition to occur. Oxidative
addition of polar reagents in which the anionic leaving group does not coordinate to the metal
center can occur at 18 e complexes.
• Oxidative addition of non-polar reagents (see below) requires an open coordination site. This is
not always true for polar reagents.
• Ligand dissociation is often required prior to oxidative addition, thus the coordinating ability of the
ligands can affect the rate.
Oxidative Addition: There are three major classes of substrates that undergo oxidative addition. We
will consider their mechanisms separately.
- Non-polar bonds: (H-H, H-CR3, H-SiR3, etc)
- Polar bonds: (R-X, H-X, RCOX)
- π-systems: (O2, MeO2CCºCCO2Me)
Thermochemistry of Oxidative Addition
A
IrI + A-B IrIII
B
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A-B A-B BDE Ir-A BDE Ir-B BDE ∆H (kcal/mol) ∆G (kcal/mol)

(kcal/mol) (kcal/mol) (kcal/mol)
H-H 104 Ir-H: 60 Ir-H: 60 -16 -6
CH3-H 104 Ir-CH3: 46 Ir-H: 60 -2 +8
CH3-CH3 88 Ir-CH3: 46 Ir-CH3: 46 -4 +6
CH3-I 56 Ir-CH3: 46 Ir-I: 45 -35 -25
Although C-H and C-C oxidative addition is unfavorable in this system, changing the ligands can
make these processes thermodynamically favored as we'll see.
1) Oxidative addition of non-polar compounds
A. Dihydrogen (H2)
Oxidative addition of H2 is a key step in the hydrogenation of alkenes and other related reactions. It is
the best understood oxidative addition of non-polar reagents. There are three major mechanisms by
which dihydrogen can undergo oxidative addition. We will see that these also apply to other non-
polar compounds.
Mechanisms of H2 Activation
Concerted
H
H H
Mn + Mn Mn+2
H H
H
Homolytic
2 Mn + H-H 2 HMn+1
Heterolytic
X Mn + H H + :B H-Mn + HB+ + X-
B
Mn B + H H Mn H Mn-H + BH
H
1. Concerted Addition of H2
Theoretical treatment of the gas-phase oxidative addition of H2 to (H3P)2Pt:
Kevin Shaughnessy
59
H3P
H
140° Pt 0.77 Å
H
H3P
2.3 - 8 kcal/mol
PH3
E H
Pt + 0.74 Å
H
PH3 JACS, 1984, 106, 6928 and 8321
H3P H
Pt
H3P H
Reaction Coordinate
H2 approaches side on rather than end on.

cis addition of H2 occurs with a low barrier, while trans addition is forbidden.
The transition state occurs early as expected for an exothermic reaction.
The transition state is similar to our discussion of the bonding of dihydrogen to metal centers.
Dihydrogen addition to Wilkinson's catalyst
K
Ph3P Cl -PPh3
Rh Ph3P Cl
Rh
Ph3P PPh3 Ph3P
+PPh3
k2 k2'
H2 k2/k2' = 10-4 H2
H PPh3
Ph3P H Rh(PPh3)2(H)2Cl
Rh
Ph3P PPh3
Cl
cis-dihydrogen addition to Vaska's complex (JACS, 1985, 107, 8049):
H
OC PPh3 H2 H PPh3
Ir Ir
Ph3P X Ph3P X
CO
Kevin Shaughnessy
60
9. Rate = kobs[Ir][H2]
10. ∆H‡ = 11 kcal/mol
11. ∆S‡ = -21 eu
12. Rate: I > Br > Cl (100:14.3:0.93)
13. kH/kD = 1.09
Stereochemistry of oxidative addition: When H2 adds to a square planar complex, it can add
along two different L-M-L' axes.
H H
H H
H H H H
A A B B
A B Ir
Ir Ir Ir
C D C D
D C
D B A C
In the case of a chelated version of Vaska's complex, a stereospecific addition is seen. The H2
approaches along the P-M-CO axis.
Ph2 H Ph2 H
Ph2
H2 P H Keq = 41 P CO
P CO Ir Ir
Ir P H
P Cl P Cl
Ph2 CO Ph2 Cl
Ph2
kinetic thermodynamic
Why does CO move initially?
H H
O C M
The p-acceptor orbital of CO helps to stabilize the H2 complex promoting oxidative addition along
that axis.
Dihydrogen complexes as intermediates:
The Kubas dihydrogen complex undergoes reversible oxidative addition to give the dihydride
(JACS, 1986, 133, 9). A variable temperature NMR study showed that at 50 °C, the 1JH-D
disappears reversibly.
H D H D
L CO L CO
W W
OC L OC L
CO CO
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61
Since population of the s* orbital is required for oxidative addition, predictions can be made about
whether a metal complex will oxidatively add H2, form an H2 complex, or fail to react with H2
based on the π-basicity of the metal center.
H H H H
Mo Mo
ν (N2)
cm-1
Mo(CO)5(N2)
2200
Mo(CO)3(PCy3)2(N2)
2150
W(CO)3(PCy3)2(N2)
2100 Mo(CO)(Ph2PCH2CH2PPh2)2(N2) R2 N2 R2
P P
Mo(CO)(i-Bu2PCH2CH2Pi-Bu2)2(N2) Mo
2050 Mo(CO)(Et2PCH2CH2PEt2)2(N2) P P
R2 CO R2
2000
1950 Mo(PMe3)5(N2)
2. Homolytic Cleavage of Hydrogen:
Although less common, there are examples of 17 e metal complexes oxidatively adding H2 by a
homolytic mechanism.
2 [(CN)5Co]3- + H2 2 [HCo(CN)5]3-
3- H 3-
3- 3-
(NC)5Co H H Co(CN)5 or (NC)5Co Co(CN)5
H
• rate = kobs[(CN)5Co3-]2[H2]
• ∆H‡ = -0.7 kcal/mol
• ∆S‡ = -55 eu
Halpern, Inorg. Chem. 1970, 9, 2616; Inorg. Chim. Act. 1983, 77, L105-L106
3. Heterolytic Cleavage:
Kevin Shaughnessy
62
Activation of H2 by heterolytic cleavage is not formally an oxidative addition. The metal retains
the same oxidation state and coordination number in the product. A base, either external or one
of the ligands, promotes the heterolytic cleavage by deprotonating the bound H2 ligand.
Heterolytic oxidative addition of H2 promoted by a base is a key step in many ionic hydrogenation
catalysts. An example is this hydride bridged Ru dimer, where the oxygen acts as a base to
promote H2 addition to give the hydroxy Ru-H. C.P. Casey, JACS, 2001, 123, 1092.
O H O
Ph Ph Ph Ph Ph
Ph Ph Tol OH O Tol HO Tol
H2
H Ph Ph Ph
Ru Ru Tol Tol + Tol Tol
Tol Ru Ru CO
Tol
Tol OC Ru H H
OC CO OC CO OC CO
COCO
Participation by an internal ligand is very common for early transition metals, activation by an
external base is less commonly observed.
H2
Sc CH3 Sc H + CH4
Sc(III) is d0 metal, so this reaction cannot involve oxidative addition of dihydrogen. Instead the
reaction occurs by a process called s-bond metathesis. The reaction likely proceeds through
initial coordination of H2 to the metal center, followed by a 4-center transition state, in which
methane is released and a Sc-H bond is formed.
H3
Cp* Cp* Cp* C Cp*
Sc CH3 Sc CH3 Sc H Sc H + CH4
Cp* Cp* H Cp*
H Cp*
H
H H
We will see that s-bond metathesis plays an important role in the activation of C-H bonds by early
transition metals as well.
B. Oxidative addition of Alkanes (C-H)
Same mechanisms as H2 oxidative addition:

1. Concerted: Mn- + H-CR3 ® (alkane complex) ® H-Mn+2-CR3
2. Homolytic: 2 Mn + H-CR3 ® Mn+1-CR3 + Mn+1-H
3. Heterolytic: M-Z + H-CR3 ® M-CR3 + HZ
General trend: sp2 C-H bonds are usually activated more readily than sp3 C-H bonds.
1. Concerted Oxidative Addition
a. Intramolecular C-H oxidative addition

Kevin Shaughnessy
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Intramolecular oxidative addition, which is often called cyclometallation is very common.
H
Ph3P Cl Ph3P
Ir Ir
Ph3P PPh3 Ph3P P
Cl Ph2
J. Am. Chem. Soc., 1969, 91, 6983
Prior coordination (agostic) allows the weakly binding C-H species to be held in close proximity to the
metal center facilitating oxidative addition.
b. Intermolecular C-H oxidative addition
The first examples of intermolecular oxidative addition of alkanes was reported by Bergman (J.
Am. Chem. Soc., 1982, 104, 352 and 1983, 105, 7190) using coordinatively unsaturated iridium(I)
complexes formed by expulsion of H2.
Cp* hν Cp*
*Cp
-H2 R-H
Ir Ir Ir
H H
Me3P H Me3P
Me3P R = CH3, Ph, R
cyclohexyl, etc.
Cp* Cp*
Ir "Cp*Ir(PMe3)" + H-Cy Ir
H H
Me3P Me3P
Rate retarded by added cyclohexane, but unaffected by

increased [benzene].
For alkanes, less sterically hindered C-H bonds add at faster rate. This presumably is due to the
greater stability of less sterically demanding alkane complexes.
Cp* hν
Cp* Cp*
-H2
Ir Ir Ir
H H H
Me3P H pentane Me3P Me3P
not formed
Oxidative addition of arenes is generally preferred over oxidative addition of alkanes.

Arene C-H: 110 kcal/mol
Alkane C-H: 95 kcal/mol
Kevin Shaughnessy
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Cp* hν C5H10:C6H6 Cp* Cp*

*Cp
-H2 1:1
Rh Rh Rh Rh
H H H
Me3P Me3P Me3P
H Me3P
1 5.4
The preference must be kinetic rather than thermodynamic. Why would arene oxidative addition
be kinetically preferred?
The importance of prior coordination has been studied by various authors for systems similar to
Bergman's Ir complex.
Cp* Cp*
Cp* -10 °C
LiHBR3 Rh C6H6 Rh
Rh PMe3
PMe3 PMe3 H
Cl H
Fast
Cp*
Cp*
Rh
Rh PMe3
PMe3
+
slow
J. Amer. Chem. Soc. 1982, 104 4240.
Kinetic studies appear to confirm the intermediacy of an arene complex.
Cp* hν
-H2
Rh + C6H6/C6D6 kH/kD = 1.04
H
Me3P H
Cp* H D hν
-H2
Rh kH/kD = 1.4
H + D H
Me3P H
H D
In a platinum system, the h2-arene adduct is stable relative to the oxidative addition product and
can be isolated and characterized. Exchange of arene protons and the Pt-H show that oxidative
addition/reductive elimination occurs reversibly. (J. Am. Chem. Soc., 2001, 123, 12724-5)
Kevin Shaughnessy
65
HB HB NH
HB NH
N
N H N H
Pt HX N H
Pt
N H N H Pt
CD2Cl2 N
∆G‡ = 12.7 kcal/mol
-78 °C
HB
N N
N = HB N = Tp
N
3
Oxidative addition often requires the presence of an open coordination site. Since alkanes are
very weak ligands, they cannot displace other ligands readily. A recent example shows the first
example of a stable product of oxidative addition of an alkane to a Pt(II) center.
2. Homolytic Activation
J. Am. Chem. Soc. 1991, 113, 5305
C6H6
N 2 (TMP)Rh + CH4 (TMP)RhH + (TMP)RhCH3
N Rh N 2 (TMP)Rh + toluene (TMP)RhH + (TMP)Rh

Ph
N
rate = kobs[(TMP)Rh]2[R-H]
∆H‡ = 7.1 kcal/mole
∆S‡ = -39 eu
(TMP)Rh
Proposed mechanism
HH
[(TMP)Rh]2 2 (TMP)Rh (TMP)Rh H C Rh(TMP)
H
(TMP)RhH + (TMP)RhCH3
3. Heterolytic cleavage: s-bond metathesis
Early transition metals (usually d0) with basic ligands (H-, R-) will heterolytically activate C-H
bonds. There are now numerous examples of this type of reactivity. For d0 metals, oxidative
addition is not possible, so the reaction must proceed by s-bond metathesis.
Cp* Cp*
13CH
Lu CH3 + 4 Lu 13CH3 + CH4
Cp* Cp*
CH3
Cp*Lu-CH3 + Cp*2Lu + CH4
CH3
Acc. Chem. Res., 1985, 51
Kevin Shaughnessy
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Is the mechanism simply electrophilic aromatic substitution?
X = CH3
CH3
6%
ScCp*2
CH3
57 %
X X k (X 105 M-1s-1)
80 °C ScCp*2 H 3.3
Cp*2Sc-H + CH3 3.4
-H2 CH3 NMe2 3.2
23 %
Cp*2Sc H2
C
ScCp*2 14 %
Late transition metals often undergo ligand-directed metallation. This is a key step in direct
functionalization of sp2 and sp3 bonds by late transition metal catalysts. These processes are
generally thought to follow a heterolytic mechanism. In some cases, C-H activation of arenes can be
achieved without prior coordination. The mechanism is thought to be similar to the ligand-assisted
routes.
Possible mechanisms include electrophilic aromatic substitution (SEAr), σ-bond metathesis

(intramolecalur heterolytic cleavage), intermolecular heterolytic cleavage, or oxidative
addition/reductive elimination. The heterolytic mechanisms are most common. Review: Kapdi, A,
Dalton Trans, 2014, 43, 3021.
Kevin Shaughnessy
67
B
SEAr H
X
M
L -HB+ X–
H
σ-bond X
metathesis
M
X L
-HX
M
H M
L L
B
H
intermol. X
activation M
L
-HB+ X–
X H
OA/RE M
L
-HX
For C-H bond activation by palladium catalysts in the presence of carboxylate anions, a σ-bond
metathesis mechanism has been implicated for both sp3 (Rousseaux, and Fagnou, J. Am. Chem.
Soc. 2010, 132, 10692-10705.and sp2 (Fagnou. J. Am. Chem. Soc. 2008, 130, 10848-10849) C-H
activation. This type of mechanism is often called concerted metalation/deprotonation (CMD) and is
typical for lower-valent late transitions metals, particularly d8 square planar complexes (Pd(II), Rh(I))
sp3
O Me
NMe2 + RCO2– N H
NMe2 Pd(PCy3)2 -PCy3
O O
O
Br Pd PCy3 Pd R
Cy3P Br Cy3P O
O
O
Me
Me N
N
H
Pd Pd O
Cy3P O H Cy3P
O O
R
R
Kevin Shaughnessy
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sp2
R3P Pd
H R3P Pd H R3P Pd
O O
O O HO O
R
R R
Kevin Shaughnessy
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4-Oxidative Addition/Reductive Elimination: Part 2
2. Oxidative addition of polar reagents
Major mechanisms:
A. Two-electron Processes
1. Concerted
R
R R
Mn + Mn Mn+2
X X
X
- Requires coordinative unsaturation

- Retention of configuration at carbon
- cis stereochemistry at the metal
- Mostly observed for oxidative addition of aryl halides
2. SN2 Oxidative Addition
M:n C X Mn+2 C + X-
- inversion at carbon
- cationic (interceptable?) intermediate
- second order kinetics
- typical SN2 reactivity patterns
- Most commonly seen with 1° and 2° alkyl halides
B. One-electron mechanisms
1. Atom Abstraction and Combination with a Second Metal
r.d.s
Mn + R-X X-Mn+1 + R
R + Mn R-Mn+1
- Typical for metals with odd electron counts

- 2:1 M:RX stoichiometry
- racemization at carbon
- rate = kobs[M][RX]
- tertiary > secondary > primary > methyl typical of free radical
- Evidence for R• (EPR, trapping, etc)
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2. Radical Chain Pathway
In• + X-R In-X + R• Initiation

R• + M R-Mn+1
Propagation
R-Mn+1 + R-X R Mn+2 X + R•
- Evidence for R• (racemization, homocoupling, disproportionation, trapping, radical clocks)

- Initiation or inhibition
3. Inner-Sphere Electron Transfer/Caged Radical-Pair Mechanism
Mn R-X Mn X R Mn+1X R cage
collapse escape
R + Mn+1X
R Mn+2 X
Mn
R-R, alkenes, alkanes R-Mn+1
- Similar to SN2, but could give racemization at carbon
4. Outer-Sphere Electron Transfer Mechanism
Mn + R-X Mn+1 + R X
R Mn+2 R• + X-
- Occurs with high barrier

- Only occurs when RX coordination (inner-sphere) is inhibited (i.e., coordinatively saturated
metals with strongly bound ligands) and SN2 pathways are relatively slow.
Ways to study mechanisms:
¨ Stereochemistry at metal and/or carbon
¨ Kinetics and thermodynamics
¨ Probes: radical traps, radical clocks, etc.
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2-electron Processes
1: Concerted Oxidative Addition: Oxidative addition of aryl halides to Pd(0)
Pd(PPh3)4 mechanism: Kinetic studies have shown that the 14-electron Pd(PPh3)2 species formed by
loss of two equivalents of PPh3 is the species that reacts with the aryl halide. Initial coordination as a π-
complex is believed to occur, followed by insertion into the C-X bond through a 3-centered transition
state.
PPh3
PPh3 PPh3
Pd PPh -PPh3 -PPh3 Ar X
Ph3P PPh3
3 Pd Pd
Ph3P PPh3
PPh3
Ph3P PPh3 Ar
Ph3P
Pd Ph3P Pd Ar Ph3P Pd PPh3
Pd
Ph3P X X X
Ph3P X
J. Organomet. Chem. 1971, 28, 287-291
Halide Effect: PhI (room temp) > PhBr (80 °C) > PhCl (no reaction at 135 °C). solvent = benzene
ArF are generally inert
Electronic Effects (Aryl Halide): Electron donating groups slow down the rate of oxidative addition,
while electron withdrawing groups accelerate the reaction: PhCl (no reaction at 135 °C) < p-Cl-
benzophenone (89%, 135 °C), < p-chlorobenzonitrile (97%, 100 °C) < 4-chloronitrobenzene (86%, 80
°C).
Stereochemistry: The initial product is presumably the cis-diphosphine complex, but the isolated
product is usually the trans-diphosphine product. In most cases, the cis intermediate cannot be
observed.
Ligand Effects: Changing the steric, electronic, and chelating properties of the ligands can significantly
affect the rate and mechanism of the oxidative addition reaction.
Ligand Size: Larger ligands can accelerate oxidative addition. They promote formation of
coordinatively unsaturated LPd(0) complexes, which are highly reactive towards aryl halides.
Electron Donating Ability: Increased electron donating ability of the ligand accelerates oxidative
addition. With P(t-Bu3), oxidative addition can occur efficiently at, or below, room temperature. ArCl
oxidative addition occurs efficiently at 25-60 °C.
Chelating Ligands: Small bite angles can accelerate oxidative addition. The (L-L)Pd(0) intermediate
is highly strained resulting in very high reactivity. For example, photochemically generated (CH2(Pt-
Bu2)2)Pt(0) will oxidatively add aryl fluorides (Chem. Ber. 1992, 125, 629). These strained complexes
are usually not good catalysts, because the resulting oxidative addition product is too stable.
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t-Bu2 t-Bu2 t-Bu2

P P C6F6 P
- CMe4 C6F5
Pt Pt Pt
P H F
P P
t-Bu2 t-Bu2 t-Bu2
In other cases, larger bite angle complexes, such as the Josiphos ligands, can promote difficult
oxidative additions of aryl tosylates (JACS, 2003, 125, 8704).
PtBu2 TsO PtBu2

P Pd P Pd Ph
Fe Cy2 P(o-tol)3 Fe Cy2
rt OTs
Mechanisms with sterically-hindered phosphines: For large cone angle ligands (i.e., P(o-tol)3, Pt-Bu3), the
stable Pd(0) complex is a 14-electron L2Pd species. Ligand dissociation occurs prior to oxidative addition
and the resulting products are either 3-coordinate LPd(Ar)X complexes or dimeric [LPd(ArX)]2 species
(Hartwig, JACS, 2009, 131, 8141-8154). Depending on the ligand and ArX, several different mechanisms
can be considered. Possible mechanisms include:
• Path A: Direct oxidative addition to L2Pd followed by ligand dissociation: This mechanism does
not occur for large cone angle ligands. With the smaller dicyclohexylphosphine ligand, this
mechanism may occur.
• Path B: Reversible associative ligand substitution of the aryl halide for phosphine followed by
rate limiting oxidative addition
• Path B': Irreversible associative ligand substitution followed by fast oxidative addition. Oxidative
addition faster than associative displacement of ArX by L.
• Path C: Reversible ligand dissociation followed by oxidative addition to the 12-electron LPd
species. Could also consider this a dissociative substitution of ArX for L, followed by oxidative
addition.
• Path C': Irreversible ligand dissociation followed by oxidative addition (oxidative addition faster
than recoordination of L).
Path B +ArX L Pd (ArX)

-L k3
k2
-ArX
k -2 +L
L
ArX, k1 Ar -L
L Ar Pd X
L Pd L L Pd X
Path A Ar Pd X X Pd Ar
L
-L L
k4 L = Pt-Bu3 L = P(o-tol)3, X = I,Br,Cl
+L k ArX AdPt-Bu2 L = CyPt-Bu2, X = I,Br,Cl
-4
k5 X = Br, Cl L = Pt-Bu3, X=Cl
Path C L = AdPt-Bu2, X = Cl
Ad = 1-adamantyl
L Pd
Path A:
𝑟𝑎𝑡𝑒 = 𝑘JKL [𝐿0 𝑃𝑑] 𝑘JKL = 𝑘. [𝐴𝑟𝑋]

Kevin Shaughnessy
73
Path B
𝑟𝑎𝑡𝑒 = 𝑘JKL [𝐿0 𝑃𝑑]
𝑘0 𝑘8 [𝐴𝑟𝑋]
𝑘JKL =
𝑘8 + 𝑘%0 [𝐿]
1 1 𝑘%0 [𝐿] 1
=R + S
𝑘JKL 𝑘0 𝑘0 𝑘8 [𝐴𝑟𝑋]
Path B': 𝑘8 ≫ 𝑘%0 [𝐿]
𝑟𝑎𝑡𝑒 = 𝑘JKL [𝐿0 𝑃𝑑] 𝑘JKL = 𝑘0 [𝐴𝑟𝑋]
Path C:
𝑟𝑎𝑡𝑒 = 𝑘JKL [𝐿0 𝑃𝑑]
𝑘U 𝑘V [𝐴𝑟𝑋]
𝑘JKL =
𝑘V [𝐴𝑟𝑋] + 𝑘%U [𝐿]
1 1 𝑘%U [𝐿]
= +
𝑘JKL 𝑘U 𝑘U 𝑘V [𝐴𝑟𝑋]
Path C': 𝑘V [𝐴𝑟𝑋] ≫ 𝑘%U [𝐿]
𝑟𝑎𝑡𝑒 = 𝑘JKL [𝐿0 𝑃𝑑] 𝑘JKL = 𝑘U
Experimental Data
ArI: Kinetic data shows first order dependence on [ArI] and zero order dependence on [L].
ArBr: Kinetic data shows a first order dependence on [ArBr]. A plot of observed rate constant (kobs)
vs. [ArBr] was linear, but had a non-zero intercept. There was no dependence on [L].
ArCl: Kinetic data shows a first order dependence on [ArCl] and inverse first order dependence on
[L]. A plot of 1/kobs vs. 1/[ArCl] was linear with a non-zero y-intercept.
Kevin Shaughnessy
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2: SN2-type oxidative addition:
General Features: Oxidative addition to Na2Fe(CO)4 (Collman, JACS, 1977, 99, 2515)
CH3I + Na2Fe(CO)4 Na[(CH3)Fe(CO)4] + NaI
Substrate reactivity
Cl
Cl Cl
Cl Cl
5 0.13 4 X 10-3 1.4 X 10-5 <1 X 10-5
X = I > Br > OTs > Cl

C10H21X
51 1 0.58 2.3 X 10-3
Stereochemistry
Na2Fe(CO)4 Na+ Fe(CO)4 1) CO O CH3

OTs
2) CH3I
99% ee 99% ee
Oxidative addition to Vaska's complex:
CH3 CH3
L X CH3I L X L I
Ir Ir Ir
OC L OC L OC L
I X
Halpern, J. Am. Chem. Soc. 1966, 88, 3511
- Rate = kobs[Ir][CH3I]
- ∆H‡ = 5-9 kcal/mol
- ∆S‡ = -50 eu
- Faster in polar solvents (reaction 10X faster in DMF than in toluene, J. Phys. Chem. 1973, 77,
290)
- Faster with more basic phosphines
- rate RX: I > Br > Cl. CH3I >> CH3CH2I >> R2CHI >> R3CI
- unaffected by radical traps or initiators
Kevin Shaughnessy
75
D D D
L X
Ir Ph Ph Ph
OC L Br [Ir] [Ir]
F F F
1:1
- ROTs slower than RBr
- Initiated by O2, AIBN, benzoyl peroxide
- Inhibited by radical traps
1-electron Processes
1. Atom Abstraction:
Reaction of Cr(II) with alkyl halides
H 2O
NH HN 2 [N4Cr(H2O)]2+ + RX [N4CrR(H2O)]2+ + [N4CrX(H2O)]2+
= N4
NH HN Espenson, Inorg. Chem., 1979, 18, 2587.
- rate = kobs[Cr][RX]
- relative rates: MeI (1) < EtI (9) < i-PrI (107) < BnBr (4.15 X 105)
- reaction with 6-bromo-1-hexene
2 [N4Cr(H2O)]2+ + Br [Cr]
[Cr]
0.022 M Cr, 0.0029 M RX: 1.6 : 1

0.044 M Cr, 0.0048 M RX: 4.9 : 1
2. Radical Chain
Radical Chain Oxidative addition of alkyl halides to Pt(II)
N CH3
hν (473 nm) N CH3
Pt + I Pt
N N CH3
CH3
I
J. Am. Chem. Soc. 1985, 107, 1218-1225
- Reaction does not occur in the dark

- Reaction inhibited by pyrene and activated by benzophenone
- Quantum efficiency dependent on [Pr•]
- Only Pr• was trapped by a radical trap
- Free radical scavenger reduced the quantum yield by 2000 X
Kevin Shaughnessy
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Initiation
N CH3 hν (473 nm)
Pt [(phen-)Pt+Me2]
N CH3
I
k = 1.5 X 107 M-1s-1
[(phen-)Pt+Me2] + I N CH3 +
Pt
N CH3
I I
atom abstraction N CH3
N CH3 Pt +
Pt I
N CH3 N CH3
I
Propagation
N CH3 k ca. 107 M-1s-1 N CH3

+ Pt Pt
N CH3 N CH3
N CH3 k ca. 6 X 103M-1s-1 N CH3

Pt + I Pt
N CH3 N CH3
I
Termination
R
R
N CH3 N CH3
+ Pt Pt
N CH3 N CH3
R = i-Pr, I
5. Inner-Sphere Electron Transfer
Oxidative addition of aryl halides to L4Ni(0)
L -L L L Ar L
Ni ArX
Ni L L Ni L + L Ni L + Ar-H
L L +L L X X
L = PEt3
- Yield of ArNiX is highest for ArCl and lowest for ArI

- ArNiX:XNi(I) ratio is largely unaffected by degree of coordination
- The reaction is not inhibited by free radical scavengers
- All aryl halides show a similar Hammet plot dependence
Kevin Shaughnessy
77
collapse Ar
L Ni L
-L X
L4Ni NiL3 + Ar-X [L3NiI ArX•-]
+L L
diffusion H-S
L Ni L + Ar•
Ar-H
X
Kochi, J. Am. Chem.Soc., 1979, 101, 6319
6. Outersphere Electron Transfer
Alkylation of Fp-
I
Fp
Fp
Cp
70 : 30
Fe
OC Br
OC Fp
Fp
Fp- > 97 : < 3
D
BsO D
D
Fp
D
BsO = O3S Br
3. Oxidative Coupling
π-bound ligands can be coupled at transition metal centers in a formal oxidative coupling. Often this
is referred to as reductive coupling because the organic fragments are reduced. It all depends on
your point of view.
oxidative
coupling
M M
reductive
cleavage
This process can be applied to the stoichiometric, or in some cases catalytic, coupling of
unsaturated molecules. A stoichiometric example is the coupling of alkynes to give a
metallacyclopentadiene. This species can be reacted with various electrophiles to give dienes or
heterocycles.
Kevin Shaughnessy
78
Ph
PMe3 Ph Ph Ph
Ti Ti
PMe3 Ph
Ph
PhPCl2
H+
Br2
Ph
Ph Ph Br Br Ph P Ph
Ph Ph
Ph Ph
Ph Ph
Ph Ph
Metallacyclobutadienes are believed to be key intermediates in the [2+2+2] cyclotrimerization of alkynes

to give arenes and heterocycles. (Mitsudo, J. Mol. Cat. A. 2004, 205, 35).
C6H13
C6H13 C6H13 C6H13 CO2Me

Cp*RuCl(cod) C6H13 Cl CO2Me
Ru
Cp*
MeO2C CO2Me MeO2C C6H13
CO2Me
C6H13 CO2Me
CO2Me
4. Reductive Elimination
Reductive elimination is the microscopic reverse of oxidative addition. Therefore the observed
mechanisms are the reverse of those we've discussed. Those that are of the most are interest are the
concerted reductive eliminations that produce C-H, C-C, or C-X bonds.
General observations (H-H, C-H, C-C):
2. rate of reductive elimination: H-C > H-H > C-C, although -∆G increases as H-H < C-H < C-C
3. The low valent MLn fragment formed upon reductive elimination must be stable
4. π-accepting ligands generally accelerate reductive elimination
5. Reductive elimination of non-polar bonds (H-H, C-H, C-C) is common, while reductive elimination
of polar bonds is less common
Halpern and Sen, J. Am. Chem. Soc., 1978, 100, 2915
Kevin Shaughnessy
79
(PPh3)4Pt + Pt(0)
Ph3P H -25 ˚C
Pt CH4 + [(PPh3)2Pt] Ph
Ph3P CH3 Ph3P
Rate = k1[Pt] Pt
k1 = 4.5 X 10-4 s-1 Ph Ph Ph3P
∆G‡ = 18.2 kcal/mol (-25 ˚C) Ph
kH/kD = 3.3
CH4: 20
D H
L2Pt + L2Pt CH3D: < 1
CD3 CH3 CD3H: < 1
CD4: 20
D CH4: < 1
H
L2Pt + L2Pt CH3D: 25
CD3 CH3 CD3H: 25
CD4: < 1
X k1 (104)
Cl 9.2 H
X P L2Pt
H 4.5 Ph > Et > CH3
3
R
CH3 1.4
OCH3 0.47
Reductive elimination is favored with more electron-donating alkyl groups (Hartwig, Organometallics,
2004, 23, 3398).
PPh2 R krel
Ph2 Ph2 Ph2 CH3 600
P Ar PPh2 P P Bn 250
Pd Ar-R + Pd CH2CF3 1.7
P heat CH2CN 1
R P P
Ph2 Ph2 Ph2 CF3 No Rxn
A. Geometric requirement
Concerted reductive elimination requires cis coordination of the ligands to be eliminated.
Ph2
P CH3 80 ˚C
Pd "Pd(0)" + C2H6
P CH3 DMSO
Ph2
Kevin Shaughnessy
80
H3C
80 ˚C
Ph2P Pd PPh2 no reaction
H3C DMSO
CD3I
I- CD3CH3 +
H3C H3C
Ph2P Pd PPh2 Ph2P Pd PPh2
H3C I
CD3
B. Ligand dissociation (dissociative)
Except for particularly facile reductive elimination (H-H or H-CR3), prior ligand dissociation is often
required.
Ph2
Ph2 CH3 Ph2 CH3 P CH3
P CH3 polar solvent 100 ˚C
P CH3 C2H6 + Pt
Pt Pt P OAc
P CH3 -OAc
P CH3 Ph2
Ph2 OAc Ph2
nonpolar
solvent
Ph2
P CH3 Goldberg, J. Am. Chem. Soc., 1999,
Pt + MeOAc
P CH3 121, 252
Ph2
Kevin Shaughnessy
81
Ph2 CH3 Ph2

P CH3 165 ˚C, days P CH3
Pt Pt + C2H6
P CH3 P CH3
Ph2 CH3 Ph2
Golberg, J. Am. Chem. Soc., 2000. 122, 962-3
Radical or interchange
Mechanistic possibilities
Ph2 CH3
P •CH3
Pt
P CH3
Ph2 CH3
Ph2 CH3 Ph2

P CH3 Direct R. E. P CH3
Pt Pt + C2H6
P CH3 P CH3
Ph2 CH3 Ph2
Ph2 CH3
P CH3
Pt
CH3
PPh2 CH 3
phosphine dissociation
Ph2 CH3 Ph2 CD3

P CH3 P CD3
Pt Pt
P CH3 C2H6 + C2D6 no C2H3D3 observed
P CD3
Ph2 CH3 Ph2 CD3
Ph2 CH3 Ph2

P CH3 165 ˚C, 300 h P CH3
Pt C2H6 + Pt
P CH3 P CH3
Ph2 CH3 4 % yield Ph2
C. Ligand assisted (associative)
Less commonly prior ligand association will accelerate reductive elimination. Normally we would
expect that coordination of electron rich ligands would make reductive elimination less favorable,
however the increased steric strain promotes the reductive elimination.
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82
2 Me3P PMe3 CH3

H Cp2Zr
Cp2Zr PMe3
Schwartz, J. Am. Chem. Soc. 1981, 103, 2687-2695
Me2 Me2
P CH3 Me3P P PMe3
Ni CH3-Ph + Ni
P Ph P PMe3
Me2 Me2
Tatsumi, J. Am. Chem. Soc., 1984, 106, 8181 (theoretical treatment)
Very sterically demanding ligands, such as (t-Bu)3P, can even induce reductive elimination of aryl
halides from Pd(II) complexes. Normally oxidative addition is an exothermic process, so the
observation of thermodynamically preferred reductive elimination is rather unusual.
(o-tol)3P X Ar
+ xs P(t-Bu)3 (t-Bu)3P Pd P(t-Bu)3 + ArX + 2 P(o-tol)3
Pd Pd
Ar X P(o-tol)3
+ 2 P(t-Bu)3 2 P(t-Bu)3
+2 P(o-tol)3 Ar X
2
Pd
(t-Bu)3P
Hartwig, Organometallics, 2004, 23, 1533-1541.
Kevin Shaughnessy
83
5-Migratory Insertion and Elimination
The third fundamental transformation involved in organometallic transformations (ligand substitution and
oxidative addition/reductive elimination being the others we've discussed) is migratory
insertion/elimination.
C L C
C 1,1 insertion +L
M A M A
M A B -L
elimination B B
C
C A L
A 1,2-insertion +L
M M B M B
B elimination -L
A C
General Features:
- There is no change in the formal oxidation state of the metal unless AB is an alkylidene or
alkylidyne.
- The groups undergoing migratory insertion must be cis to one another. In complexes where the
cis coordination sites are blocked by strongly coordinated ligands insertion or elimination
processes are not possible.
- An open coordination site is created during migratory insertion. Therefore, for the reverse
reaction--elimination--to occur, an open coordination site must be generated by ligand
dissociation.
- In cases where C is a chiral carbon center, the reaction usually occurs with retention of
configuration.
- Cases where C migrates to AB followed by coordination of L in place of C, and where AB

migrates to C followed by coordination of L in place of AB are both known.
1,1-Migratory Insertion: Insertion of CO:
Most of the early mechanistic work has been carried out on iron and manganese alkyls.
A. Kinetics and Mechanism:
CH3 L
OC CO k1 OC CO L
OC CO
Mn Mn CH3 Mn CH3
OC CO k-1 OC k2 OC
CO CO O CO O
−d[MeMnCO5 ] k1k2[L][MeMnCO 5 ]
rate = =
dt k −1 + k2[L]
i. If k-1 is very small relative to k2[L], then the rate expression is simplified to:
Kevin Shaughnessy
84
−d[MeMnCO5 ]
rate = = k1[MeMnCO 5 ]
dt
ii. If k-1 is large relative to k2[L], then the equation becomes:
rate = =
dt k −1
iii. If k-1 and k2[L], have similar magnitudes, then a complex rate expression is observed that
displays saturation in the ligand concentration dependence..
rate = = = kobs [MeMnCO5 ]
dt k −1 + k2[L]
k1k2[L]
kobs =
k−1 + k2 [L]
Under pseudo-first order conditions ([L] >> [MeMn(CO)5], a plot of 1/kobs vs. 1/[L] will have slope =
k-1/k1k2 and y intercept = 1/k1.
B. Stereochemistry at the Metal:
For the migratory insertion of CO into a Mn-Me bond, two limiting mechanisms could be
envisioned. Methyl migration to a bound CO (A), or CO migration to the Mn-Me bond (B).
CH3 CH3
OC CO OC CO
Mn Mn
OC CO OC CO
CO CO
A B
To address this issue, Calderazzo looked at the migratory insertion of CH3Mn(CO)5 labeled with
13CO cis to the methyl substituent. There are 4 possible stereochemical outcomes considering
both mechanisms. (J. Organomet. Chem., 1967, 10, 101; Angew. Chem. Int Ed. Engl. 1977, 16,
299)
L 13CO
OC CO OC CO
Mn CH3 Mn
OC 13C H3C
C L
13CO CO
O O CO
OC CO L 1 2
Mn
OC CH3 13CO 13CO
CO
OC CO OC CO
Mn Mn CH3
OC L OC
L O
O CH3
3 4
When the reaction is performed, a 1:2:1 mixture of 1, 2, and 3 was formed. Which mechanism is
responsible for this product distribution?.
Kevin Shaughnessy
85
A more recent example used a chiral rhodium complex (Organometallics, 2001, 20, 2431). The
presence or absence of iodide determined whether the compound existed as an acyl iodide
complex or a methyl carbonyl complex. By looking at the stereochemistry of the migratory
insertion/deinsertion using the chemical shift of the methyl groups, the nature of the migration
could be determined..
BF4- BF4-
AgBF4
Rh CH3 + Rh Rh Rh
I CO + CH3
P P P P
Ph2 I O Ph2 CH3 Ph2 CH3 Ph2 CO
O Bu4NI
1a 1b 2a 2b
Major: δ 2.22 Major: δ 1.10
MInor: δ 2.85 Minor: δ -0.26
C. Stereochemistry at Carbon
For concerted migratory insertion or elimination, carbon stereochemistry is nearly always

retained.
D PPh3
CO D Cp
t-Bu THF
CO t-Bu Fe(CO)PPh3
Fe
D
D O
Cp
Whitesides, J. Am. Chem. Soc., 1974, 96, 2814
Br PPh3 CO Br PPh3
Pd Pd
Ph3P Ph3P O
Gazz. Chim. Ital, 1973, 103, 793
H H
H Ph
Ph
D. Aptitude for Migration:
The identity of R has a significant effect on the aptitude to undergo migratory insertion to form an
metal acyl. Migratory insertion ability cannot be easily correlated to M-R bond strength.
R L' L'
LnM LnM
CO R
O
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86
R M-L BDE Insertion/Elimination

PhCH2 29 Slower insertion than CH3
CH3CO- 39 Elimination
CH3 44 Fast insertion
CF3 49 Elimination
Ph 49 Slower insertion than CH3, but the product is more stable
H 59 Elimination
O CH3
(OC)4Re Ph
O CH3 O CH3 7
Ph Ph
(OC)4Re (OC)3Re
O O
7/8 = 50 CH3 Ph
CH3 migration is 30 X faster
(OC)4Re
than Ph migration
J. Am. Chem. Soc., 1980, 102, 2723 8 O
E. Accelerating Insertion:
• Sterically bulky ligands: Insertion reduces the steric strain in the metal complex.
• Lewis acids: Coordinate to the oxygen of CO increasing the d+ on C. Also coordinates

strongly to the acyl oxygen accelerating ligand trapping.
• Increased electrophilicity of the metal center (π-acid ligands, cationic complexes). Makes the
carbonyl more electrophilic towards attack by the migrating nucleophile.
• Oxidation of the metal center: Increased lability of 17 electron complexes may play a role in
addition to the increased electrophilicity of the metal center.
1,2-Migratory Insertion of Alkenes or Alkynes
Important catalytic processes such as alkene hydrogenation and olefin polymerization involved migratory
insertion of alkenes.
L H
LnM LnM LnM LnM
H H L
H
H migrates to alkene Potential agostic
intermediate
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87
John Bercaw (Cal Tech) has carried out a detailed study of the reversible migratory insertion of a stable
Nb(III) olefin hydride complex. JACS, 1985, 107, 2670.
Cp* H C Cp* Cp*

2
CH2 L
Nb Nb Nb
H H L
Cp* Cp* L = CO, NCR Cp*
• The Nb olefin complex has a planar cis-olefin hydride geometry.
• The Nb-Ethyl complex cannot be observed directly. It can be inferred by exchange of the
hydride into the ethylene ligand and by trapping with external ligands.
• Rate of formation of the NbEt(L) complex has a first order dependence on L, consistent with a
fast preequilibrium migratory insertion and slow trapping by L. The rate law is identical to that
discussed above for CO insertion.
• VT-NMR studies of this system by magnetization transfer shows two dynamic processes.
o A relatively fast process that exchanges the hydride with the terminal ethylene
protons.
o A slower rotation of the ethylene ligand.
Cp*H12C Cp*H22C Cp*H22C

CH22 Slow CH12 Fast CH1H
Nb Nb Nb
H H H1
Cp* Cp* Cp*
H = -3.1 ppm
H1 = 0.5 ppm
H2 = -0.4 ppm
Kevin Shaughnessy
88
• Migratory insertion rate for substituted styrenes showed that more electron rich styrenes gave
slightly faster insertion rates, consistent with a small positive charge developing on the alkene
carbon next to the aromatic ring.
• In comparing alkenes a combination of steric and electronic factors contribute: propylene >>
styrene ≥ ethylene. (Note that this is not the universal trend. Often ethylene inserts fastest).
Again, these results are consistent with a small positive charge developing on the substituted
alkene carbon.
• Although there are some electronic effects, they are small. The reaction is essentially
concerted, but the M-C bond forms slightly before the C-H bond, which results in the
development of some charge.
R δ– δ+
Cp*2Nb Cp*2Nb R Cp*2Nb R
H H H
General features of migratory insertion of alkenes:
A. Stereoselectivity of Insertion: Migratory insertion results in syn-addition across the alkene,

although other processes may cause isomerization after migratory insertion.
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89
Insertion L R
M M M
R ß-Elimination R L
Agostic
species
B. Regioselectivity of Insertion: The regioselectivity of the insertion depends on the steric and
electronic properties of the alkene/alkyne and the metal species.
Typically steric factors will result in a thermodynamic preference for the sterically less hindered
carbon to be bonded to the metal center. Hydrozirconation of alkenes with the Schwartz reagent
is a good example of this thermodynamic preference. (Pure Appl. Chem., 1980, 52, 733)
H H
Cp2Zr Cp2Zr Cp2Zr
Cp2Zr Cl
Cl Cl Cl
For alkenes with strong electron withdrawing or donating groups, electronic factors often become
more important than steric ones. (J. Am. Chem. Soc., 1997, 119, 5257)
H3C CO2H (dppe)2Pd, D2 H3C CO2H D CO2H

D D +
H H H H H3C
ß-H
Elim
Pd-D
H3C CO2H D CO2H

H H H3C H
D Pd H Pd
Styrene usually undergoes insertion to place the metal in the benzylic position, where it is
stabilized by coordination to the arene. The opposite regioisomer can sometimes be obtained
when the metal is very sterically hindered.
C. Geometric Requirement:
The M-R bond and the alkene must be able to adopt a coplanar geometry for insertion (or
elimination).
For the COD iridium complexes below, 9 undergoes insertion 40 times faster than 10, although
both have the alkene and H in cis-coordination sites.
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90
H PPh3
PPh3 H
Ir Ir
H H
PPh3 PPh3
9 10
D. Insertion into M-H versus M-R:
Migratory insertion into M-H bonds occurs at much higher rates than insertion into M-R bonds.
As in CO migratory insertion, alkene insertion into M-R is thermodynamically favored over M-H
insertion. Therefore, the preference for M-H insertion must be due to kinetic factors, not
thermodynamic factors. One example of the difference in activation energies was reported by
Brookhart (J. Am. Chem. Soc., 1992, 114, 10394)
Cp' Cp' Cp'

HBF4 H-Mig
Rh Rh Rh
L H L
L
H
Cp' Cp'
Et-Mig
Rh
Rh
L
L
Cp' L ∆G‡ H-Mig ∆G‡ Et-Mig

(kcal/mol) (kcal/mol)
Cp* P(OMe)3 12.2 22.4
Cp* PMe3 12.1 23.4
Cp P(OMe)3 15.0 23.4
Cp PMe3 15 24.7
The difference in activation energies suggests kH/kEt = 106 - 108.
Migratory Insertion to M-heteroatom bonds
Although less common, metal alkoxides and amido complexes can undergo migratory insertion of olefins
to give C-O/N bond formation. Most commonly this is seen for intramolecular reactions. In intermolecular
reactions, another possible mechanism is nucleophilic attack by the O or N on the bound alkene. We will
discuss this in chapter 14.
The mechanism for migratory insertion is generally a syn-addition as seen with H or C.
Kevin Shaughnessy
91
R
Et3P O R' Et3P
Rh O R
(Et3P)4RhH + D
Et3P D R'
50 °C
C6D6
(Et3P)2Rh H (Et3P)2Rh H
O R O R
D
R' D R'
H H
JACS 2006, 128, 9642
Migratory Elimination
A. ß-Hydride Elimination: Elimination is the microscopic reverse of 1,2-insertion, therefore the

mechanisms must be the same. In particular, ß-H elimination requires an open coordination site, and
that the M-C-C-H group can become coplanar.
For 18 electron complexes, a ligand must always dissociate to form an open coordination site cis to
the alkyl group undergoing ß-H elimination. Ligand dissociation may, or may not, be rate limiting.
-PPh3
Fe Fe Fe
OC OC OC
+PPh3
Ph3P H H
PPh3
Fe D. L. Reger, J. Am. Chem. Soc. 1976, 98, 2789
OC PPh3
H
Experimental observations
1. Only alkene products were isolated.
2. Decompositions of 1,1-d2 or 2,2-d2 butyl complexes resulted in complete scrambling of

deuterium in the 1-butene product.
3. First order kinetics with a very small kinetic isotope effect for 1,1-d2 or 2,2-d2 butyl complexes.
4. Reaction is completely retarded in the presence of excess PPh3. Other Lewis bases (THF or
dioxane) also slow down the reaction, but to a lesser extent.
5. Starting material recovered from reactions stopped after less than one half-life showed
extensive scrambling of deuterium throughout the alkyl chain.
Kevin Shaughnessy
92
For 16 electron complexes, prior ligand dissociation is not required with the exception of Pd(II) and
particularly Pt(II), which do not like to become 18e complexes.
Whitesides has studied the thermal decomposition of Pt dialkyls. Decomposition of (Ph3P)2PtBu2

gives butane and butene. The rate of decomposition is inversely dependent upon [PPh3]. (J. Am.
Chem. Soc., 1972, 94, 5258; ibid., 1973, 95, 4491, ibid, 1976, 98, 6521; Organometallics, 1986, 5,
1473)
Ph3P heat
Pt [(Ph3P)2Pt] + +
Ph3P
krel = 104
+ PPh3
-PPh3
Ph3P Ph3P
Pt Pt
H
The platinacyclopentane analog undergoes decomposition 10,000 times more slowly. This reaction
most likely goes by a radical mechanism. However larger platinacycles undergo decomposition at a
similar rate to the dibutyl complex and by the same mechanism.
Ph3P
Pt [(Ph3P)2Pt] +
Ph3P krel = 1
Ph3P
Pt [(Ph3P)2Pt] +
Ph3P krel = 104
B. b-Carbon Elimination
As discussed above, there is a much higher barrier to hydride migration compared to alkyl
migration, thus a strong kinetic preference for hydride migration. These results suggest a similar
preference for ß-H elimination over ß-alkyl elimination.
ß-H Elim CH3 H ß-Me Elim

LnM LnM LnM LnM
H CH3
H CH3
Typically ß-alkyl elimination is only observed where there is a large amount of strain in the C-C
bond, or where there is no ß-H to undergo elimination. ß-Alkyl elimination is more common with
highly electrophilic d0 metal complexes.
Kevin Shaughnessy
93
Tobin Marks, J. Am. Che.m Soc., 1993, 115, 3392
CH2 CH3
Cp*2Zr Cp*2Zr Cp*2Zr
L CH3
L = [CH3B(C6F5)3]-
n
CH3 CH3
Cp*2Zr Cp*2Zr
n
Murakami, J. Am. Chem. Soc. 2006, 128, 2166-2167
i-Pr
H3C O
O 10 mol% Ni(cod)2
E N i-Pr
E CH3 10 mol% iPr
iPr
CH3
E E N i-Pr
CH3 Ph
Ph CH3
E = CO2Me H3C i-Pr
Kevin Shaughnessy
94
H3C O
E
E CH3
CH3
E
Ph E CH3
H3C LNi(0)
H3C O CH3
E
E CH3 NiL
E
E Ph
Ni CH3 O
H3C L
Ph CH3
CH3
H3C
Ph CH3
Ph
E E L
O CH3
Ni
E Ni E
L O
H3C CH3
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6-Metal-Ligand Multiple Bonds
Nomenclature
R
L nM L nM R L nM C L nM O L nM N L nM N
R R
name carbene carbyne carbide oxo imido nitride
alkylidene alkylidyne nitrido
Type L or X2 LX2 or X3 X4 X2 X2 X3
#e 2 or 4e 6e 6e 4 or 6e 4 or 6e 6e
Bonding in Carbenes
Recall from Chapter 2 of the notes that there are two limiting classes of carbenes: electrophilic (Fischer)
carbenes and nucleophilic (Schrock) carbenes.
R R
M M
R R
Electrophilic (Fischer) carbene Nucleophilic (Schrock) carbene
Fischer carbenes
• Low oxidation state, late transition metals
• π-acceptor ligands on M
• π-donor substituents (R) on the carbene
Fischer carbenes can be considered as neutral 2 e ligands (L-type) derived from singlet carbenes.
Since the carbene is acting as a s-donor, it has a ∂+ charge and acts as an electrophilic center.
Schrock carbenes
• High oxidation state, early transition metals
• non-π-acceptor ligands on M
• non-π-donor substituents (R) on the carbene
Schrock carbenes are formally considered as X2-type ligands derived from triplet carbenes.
The carbene carbon has a partial negative charge and acts as a nucleophile.
Kevin Shaughnessy
96
Fischer Carbenes
E. O. Fischer first reported carbene complexes in 1964. (Angew. Chem. Int. Ed., 1964, 3, 580). See
Chapter 2 of the notes for methods of preparing Fischer carbenes.
Metal-Ligand Interactions
Fischer carbenes are considered L-type 2-electron donors. The metal-carbon double bond is
considered to derive from s-donation of the carbon lone pair to the metal and significant π-back
donation from the metal. Note that for Fischer carbenes, there is usually one, or two, π-donor
substituents attached to the carbene carbon that also compete for the empty p-orbital. Arduengo-
type NHC ligands have two N-donors as part of a heterocyclic ligand that significantly occupy the
carbene p-orbital. Initially, it was thought that there was little if any π-back donation. Recent results
show that there is significant π-back donation. Approximately 15-25% of the metal-carbene
interaction is calculated to be due to π-back bonding, which is similar to more typical Fischer
carbenes (Organometallics, 2018, 37, 275). Despite this, the metal-NHC interaction is typically
drawn with a single bond, based on the earlier understanding.
R N
M M
N
R
Typical Fischer Carbene Metal-NHC complex
Electrophilic Reactivity
MLn O
R E R E
Much of the reactivity of Fischer carbenes is directly analogous to the reactivity of carboxylic acid
derivatives. Both have electrophilic carbon centers with leaving groups.
A. Nucleophilic attack
OMe RNH2 NHR

(OC)5Cr (OC)5Cr + MeOH
Ph Ph
B. “Enolate” reactivity
1) BuLi 1) BuLi
O 2) MeOSO2F O 2) MeOSO2F O
(OC)5Cr (OC)5Cr (OC)5Cr
Kevin Shaughnessy
97
Note that the NHC-type carbenes typically do not show these types of reactivity.
Schrock Carbenes
The first nucleophilic carbenes were prepared by Schrock in an effort to prepare a homoleptic
tantalum(V) alkyl. (Acc. Chem. Res., 1979, 12, 98) See notes Chapter 2 for details.
Metal-Ligand Interaction
In the case of Schrock-type carbenes, the metal carbon double bond is considered to be two
covalent bonds. All four electrons in the metal-ligand interaction are in "ligand-like" orbitals, so the
Schrock carbene ligand is considered to be an X2-type ligand (R2C2-) that acts as a 4-electron donor.
It thus acts as a s-donor and a π-donor to the metal center. Because of the significant electron
density on the carbene carbon, it tends to behave as a base or nucleophile.
σ*
π* Metal-like orbitals
R M d orbitals
M
R
Typical Schrock Carbene triplet carbene
Ligand-like orbitals
σ
Nucleophilic reactivity
A. Lewis acid adducts
CH2 AlMe3 AlMe3

Cp2Ta Cp2Ta
CH3 CH3
B. Addition to carbonyls
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98
O
H
H CO2 R R R t-Bu
C C C
t-Bu + [ Np3TaO]x
t-Bu O R
+ [ Np3TaO]x
Np3Ta R OCH3 R t-Bu
t-Bu + [ Np3TaO]x
O O
Cl H3CO
Np3Ta
O R Cl R NMe2 R t-Bu
t-Bu + [ Np3TaO]x
R Me2N
The Tebbe reagent is particularly useful for the conversion of esters to vinyl ethers. It will olefinate
carbonyls without enolizing a-stereocenters.
Cl
Cp2TiCl2 + 2 AlMe3 Cp2Ti AlMe2 + Me2AlCl + CH4
C
H2
O
H 3C H
O N
O
O R H
H 3C H CH3
O H
H 2C Cp2Ti CH2 + ClMe2Al N
R H
CH3
H 94 % (Pure Appl. Chem., 1983, 55, 1733)
Reaction of carbenes with unsaturated alkenes and alkynes
Fischer Carbenes
Reaction with alkenes to give metalacyclobutanes. The metalacyclobutane can decompose either by
release of an alkene or by reductive elimination to give a cyclopropane.
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99
OMe
OMe
OMe
OMe
(OC)5Cr (OC)5Cr (OC)5Cr
Ph
Ph OMe
Ph OMe
Ph OMe
+ (OC)5Cr
MeO H
Olefin Methathesis
OMe Ph OMe
Ph OMe Ph
Ph
(OC)5W (OC)5W (OC)5W +
Ph Ph Ph
Ph Ph
CH3
H CH3 CH3
(OC)5W (OC)4W CH3
Ph CH3 Ph CH3
Ph H
Schrock Carbenes
Nucleophilic carbenes react with alkenes to form metalacyclobutanes, which can undergo a variety of
rearrangement processes.
Cl DMAP
Cp2Ti AlMe2 t-Bu Cp2Ti t-Bu
C toluene
H2
These titanacyclobutanes undergo rearrangements to the more stable 2-phenyl substituted products.
Cp2Ti Ph Cp2Ti
Ph
Ph Ph
Cp2Ti Ph Cp2Ti Cp2Ti + others
D D D
The titanacyclobutanes undergo exchange with free olefins to give new metallacycles. This
transformation will play an important role in our discussion of metathesis.
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Ph Ph
Cp2Ti Ph + R
Ph
Cp2Ti R Cp2Ti + R
CH3
H 2C C C
CH3
Cp2Ti + R
Metal-heteroatom multiple bonds
Metal-oxo and –imido complexes
Bonding
Oxo and nitrido ligands are considered to be X2-type ligands with a -2 charge. They are typically drawn
as M-L double bonds. For both O and N, there is an additional lone pair in a p-orbital that can potentially
bond with the metal in a dative bond. Considering this bonding, the oxo or nitriido would be considered
an LX2 ligand and a 6 electron donor. Oxo and nitrido ligands are most commonly found on metals with
low d-electron counts (d0–d2), so the extra electron donation is favorable.
potenial dative bond

M Y
L nM Y Y = O, NR
In the case of imido complexes, this additional bonding could potentially be

determined based on the M-N-R bond angle. Angles near 180° might
suggest an sp-hybridized atom. In fact, most metal-nitrido complexes have 176.4°
linear structures, even in cases where the additional bond would formally Ph
Ta N
result in exceeding the 18 electron count. It appears that there is little energy Cl
difference between the sp2 and sp-hybridized nitrogen and that steric factors
favor the linear structure.
4e imido: 18 e
6e imido: 20 e
Oxo ligands more typically act as bridging ligands between metals than as terminal ligands. MnO4–,
OsO4, and RReO3 are examples of stable complexes with terminal oxo ligands. A more typical example
is TiO2 (titania), which is a networked solid that is insoluble in all solvents. Non-homoleptic metal oxo
complexes are also typically polymeric. Titanocene oxo exists as a polymeric structure with an O-Ti-O-Ti
repeat unit. These types of structures are generally completely insoluble and cannot be fully
characterized. Oxo ligands can be associated with up to 6 metal centers.
Kevin Shaughnessy
101
O
Cp* Cp
CH2 + O O
Ti CH2 Ti O Ti Ti n
Cp Cp2 Cp2
Cp*
Ph2 2-
Ph Py O
O O Ph P
Ph Cr O O O
O O Ph O Zn Zn O O Mo O
O
O
O
O
O Py Ph2P
O O PPh2 O
O O O PPh Mo
O O
Cr Cr 2
Py O O O Mo O Mo O
O O
O Ph2P Zn Zn
O O O O O Mo O
O
Ph P O Mo O
Ph Ph2 O
O
µ3-oxo ligand µ4-oxo ligand
µ6-oxo ligand
Synthesis of metal-oxo and –imido complexes
Metal-oxo complexes: Metal oxo complexes are typically prepared by oxidation resulting in delivery of an
oxygen atom from various oxidants (O2, NaOCl, PhIO).
Cp O2 Cp
O
Nb Cl Nb
Cp Cp Cl
+ +
OH2 O
O PhIO
O O O
Cr Cr + PhI + H2O
N N CH3CN N N
OH2
Metal-imido complexes: Metal-imido complexes can be prepared in a number of ways. Metal-oxo ligands
can be converted to imido ligands either by direct reaction with amines and release of water or using
nitrene transfer reagents, such as Ph3P=NR. α-Elimination from amido complexes using a basic ligand,
such as a carbanion ligand or another amine, is another common route to imido complexes.
Kevin Shaughnessy
102
Oxo replacement
O NtBu
OsO4 + H2Nt-Bu Os + H 2O
O
O
O NtBu
OsO4 + 2 Bu3P=NtBu Os + 2 Bu3PO
O
NtBu
Elimination
LiNHCH3 75 °C
Zr CH3
Cl Zr CH3 Zr + CH4
NHCH3 NCH3
Bergman, R. G., JACS, 2004, 126, 1018
Reactivity
Atom transfer reactions: Metal-oxo complexes are common intermediates in the catalytic oxidation of
alkenes to expoxides or vicinal diols. Metal-imido compounds can do similar reactions to give aziridines
or amimoalcahol products.
cat (4 mol %) Actve catalyst

NaOCl Ph H H
Ph
N N
NaH2PO4 buffer O Mn
CH2Cl2 er: 96:4 tBu O O O tBu
84% yield
JACS, 1991, 113, 7063 tBu tBu
O
O
N Os O O O OH
O 2 H2O HO
O N Os N Os
Ph O O O OH HO
Ph Ph
O
NR
N Os R
O O N 2 H2O O OH RHN
O N Os N Os
Ph O O HO
Ph O OH Ph
L = chiral quinine or quinidine derivative in place of pyridine gives
asymmetric dihydroxylation developed by K. B. Sharpless.
[2+2] cycloadditions: Metal-heteroatom π bonds undergo [2+2] cycloadditions with unsaturated species to
give metallocyclobutane/ene species. In the case of early transition metals, this species is typically
stable. With later transition metals, the azametallacycle will often undergo reductive elimination to give an
aziridene.
Kevin Shaughnessy
103
t-Bu
NtBu Ph Ph N
Cp2Zr NtBu
Cp2Zr Ph Cp2Zr Ph
O
Ph Ph
Bergman, R. G. JACS, 1988, 110, 8731
t-Bu2 iPr t-Bu2Ar t-Bu2

P H2C CH2 P N H2C CH2 P CH2 Ar
Ni N Ni Ni N
CH2
P P P
t-Bu2 iPr t-Bu2 t-Bu2
Che, C.-M., JACS, 1999, 121, 7164
Reactions with C-H bonds: Metal-oxo and –imido complexes will often activate C-H bonds in alkanes and
arenes. Cytochrome P450 uses an Fe(V)-oxo porphyrin complex to oxidize organic compounds in order
to make them more water soluble so they can be eliminated from the body. A common mechanism is H-
atom abstraction by a Fe(V) oxo to give a carbon radical and an Fe(IV) hydroxide. The carbon radical
can then abstract hydroxyl radical to give Fe(III) and an alcohol product.
H R •R
O OH
porphyrin N N N N N N + ROH
Fe Fe Fe
N N N N N N
SCys SCys SCys
Fe(V) Fe(IV) Fe(III)
O2
Metal-imido complexes of early transition metals will react with C-H bonds to reversibly give metal alkyl
amido complexes.
75 °C
NtBu
Zr NHtBu Zr Zr NHtBu
CH3 C 6H 6
+ CH4
Bergman, R. G., JACS, 2004, 126, 1018
Kevin Shaughnessy
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7-Nucleophilic and Electrophilic Attack on Ligands
Ligands bound to metal centers often have quite different reactivity from the free compound. Many bound
ligands can be modified or removed from the metal center by nucleophilic or electrophilic reactions. Often
these reactions involve direct attack on the bound ligand.
Types of Reactions:
• Nucleophilic attack: Favored for metals that are weak π-bases and good s-acids (i.e., complexes
with net positive charges or π-acidic ligands). Ligands bound to electrophilic metals will tend to
be electrophilic themselves.
PhLi O
W(CO)6 (OC)5W
Ph
CH3 CH2
Cp2Ta + CH2PMe3 Cp2Ta + Me4P+
CH3 CH3
• Electrophilic attack: Favored for electron rich metals that act as weak s-acids, but strong π-bases
(i.e. low valent metals, or those with net negative charges and/or electron donating ligands).
Ligands bound to π-basic metals tend to be electron rich, and act as nucleophiles.
O Me3O+ BF4- O CH3

(OC)5W (OC)5W
Ph Ph
+
Cp Cp
+CPh
3
OC CO OC CO + HCPh3
Mo Mo
OC H OC
• Addition reactions: When a ligand is attacked by a nucleophile to give a new ligand that remains
bound to the metal, it is called an addition reaction.
• Abstraction; If attack on the ligand results in the ligand, or part of it leaving the metal center, it is
referred to as an abstraction.
Nucleophilic Attack
Nucleophilic Attack on CO
CO is prone to attack by nucleophiles when coordinated to weakly π-basic metals. We have already
seen that alkyl lithium reagents will alkylate CO. Increasing the electrophilicity of the metal center
allows weaker nucleophiles like water or alcohols to attack.
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105
+ H2O O HO O
CO H
OC CO H2O OC CO B: OC CO - CO2 OC CO
Mn Mn Mn Mn
OC CO OC CO OC CO OC CO
CO CO CO CO
O
CO CO +
OAc MeOH OMe
(bipy)Pd (bipy)Pd -OAc (bipy)Pd + HOAc
OAc OAc OAc
As we’ve discussed before, N-oxides are strongly nucleophilic reagents that can be used to abstract
CO ligands. (J. Organomet. Chem. 1979, 173, 1-76) The ligand substitution occurs exclusively cis to
the phosphine.
Et3N O O
CO PPh3
Ph3P CO Et3NO Ph3P CO L Ph3P CO
Mo Mo Mo + CO2 + Et3N
OC CO OC CO OC CO
CO CO CO
Nucleophilic Attack on Electrophilic Carbenes:
Electrophilic carbenes are prone to nucleophilic attack as we’ve previously seen. The reactivity is
similar to that of carbonyl derivatives in organic chemistry. This includes Michael-type additions to
conjugated carbenes.
OMe RNH2 NHR

(OC)5Cr (OC)5Cr + MeOH
Ph Ph
OMe O OMe O
H+
(OC)5Cr (OC)5Cr
J. Organomet. Chem., 1974, 77, 345
Nucleophilic attack on metal acyls:
Nucleophilic attack on metal acyls to give carboxylic acid derivatives, aldehydes, and ketones is well
precedented. Depending on the type of nucleophile, two different mechanisms can occur. With
weaker protic nucleophiles (H2O, ROH, R2NH, etc), nucleophilic attack occurs directly on the acyl
carbon in a nucleophilic acyl substitution-type mechanism. The palladium ends up as a palladium
hydride, that can be deprotonated to return to Pd(0). Strong hydride or organometallic reagents tend
to add to the metal followed by reductive elimination.
Kevin Shaughnessy
106
Br
Ph3P Pd PPh3 Br O
Br HNu HO Nu Ph3P Pd PPh3
Ph Nu
Ph3P Pd PPh3 Ph H
HNu = H2O, ROH, HNR2
O Ph RM
R O
Ph3P Pd PPh3 Pd(PPh3)2 Ph R
O Ph
M = SnR’3, ZnX, BX2
R = H, alkyl, alkenyl, aryl, etc
Nucleophilic Attack on Polyene and Polyenyl Ligands:
Polyenes such as benzene and butadiene typically react with electrophiles rather than nucleophiles.
Coordination to an electron deficient metal center reverses this normal reactivity (umpoulong).
Coordinated polyenes and polyenyls tend to react with nucleophiles.
The reactivity of polyenes can be predicted based on their structures. Qualitative rules were first
developed by Green, Davies, and Mingo (Tetrahedron, 1978, 34, 3047). The Green-Davies-Mingo
rules were developed for 18 electron complexes reacting under kinetic control, and only apply directly
to those systems.
Green-Davies-Mingo Rules:
1. Polyenes (even hapticity or Ln ligands) react before polyenyls (odd hapticity or LnX ligands)
2. Open ligands react before closed ligands
3. Open polyenes react exclusively by terminal addition. Open polyenyls usually react by
terminal addition unless the metal is π-basic.
When in conflict, rule 1 takes precedence over rule 2.
Based on these rules, the order of polyene and polyenyl reactivity can be predicted.
> > > >> > > >
Odd, Closed
Even, Closed Even, Open
Even, Odd, Cp
Fe Open Mo Open
OC Ph2P Mo
OC PPh2
Odd, NO
Open
Although the Green-Davis-Mingo rules are qualitative, these rules often predict the atom(s) with the
highest coefficient of the LUMO. Since the reactions are under kinetic control, attack of the atom with
Kevin Shaughnessy
107
the largest coefficient will be favored. For non-cyclic polyenes, this is generally the terminus of the
polyene.
Nucleophilic attack on a polyene:
• Decreases the hapticity by 1

• Results in formation of an anionic polyenyl ligand
• Does not change the metal oxidation state
• Nucleophilic attack is always on the terminus of the polyene
CH3
MeMgX
OC Mo Cp
OC Mo Cp
OC
OC
Mo(II) Mo(II)
Nucleophilic attack on a polyenyl:
• Decreases the hapticity by 1

• Results in formation of a neutral polyene ligand
• Reduces the metal by 2 oxidation states (reductive elimination)
• Nucleophilic attack is usually on the terminus, unless the metal is strong π-donating. Then it
may be in the center of the polyene (allyls).
CN
NaCN
OC Fe CO OC Fe CO
OC OC
Fe(II) Fe(0)
h2-Olefin complexes:
Alkenes bound to electrophilic metals, particularly Pd(II), Pt(II), Fe(II) are prone to attack by a
wide range of nucleophiles.
Fe Fe
OC Nu- OC
OC OC Nu
Nu- = -OR, -SR, R2NH, enolates, enamines, cuptrates
There are two mechanisms by which nucleophilic attack on a bound alkene can occur. Direct
attack on the bound ligand, or initial coordination to the metal followed by migratory insertion.
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Nu- Nu trans attack

Nu bonds to more substituted C
MLn
MLn
Nu- cis attack
Nu bonds to least
MLn MLn Nu MLn substituted C
Nu
The Wacker oxidation
The most important application of nucleophilic attack on alkenes is the “oxidation” of alkenes to
ketones or aldehydes with water in the presence of Pd(II). Stoichiometric versions of this reaction
have been known for more than a century. (Am. Chem. J., 1894, 16 , 255)
PdCl2 O
+ Pd(0)
R H2O R CH3
R = H, alkyl
It was not until the 50’s that researchers at Wacker Chemie developed a system to reoxidize
Pd(0) allowing the reaction to be catalytic. In fact a cascade of reactions is used to convert
ethylene to acetaldehyde using oxygen as the stoichiometric oxidant. This process is the major
industrial route to acetaldehyde, and can be used to make methyl ketones of higher alkenes.
O
1/2 O2 + 2 H+ 2 Cu(II) Pd(II) + 2 H+
H
H2O 2 Cu(I) Pd(0) + H2O
This reaction depends on the coordination of alkenes to the Pd center, so it is very sensitive to
the structure of the alkene. Ethylene works very well as do 1-alkenes. Internal alkenes are less
effective, and tri- and tetra-substituted alkenes generally to not bind strongly enough to react.
Kevin Shaughnessy
109
PdCl2
CuCl2 O
O2
OAc OAc
H2O
O PdCl2 O
CuCl2
O
O2
H H2O H
O O O
steps Synthesis, 1984, 369
H H
O
The original mechanism proposed for the Wacker oxidation was based on the rate expression
determined for the reaction.
k[PdCl2−
4 ][C 2H 4 ]
Rate = − 2
[Cl ] [H + ]
The rate expression implies that two chlorides and a proton are lost in the coordination of
ethylene to the Pd center. Based on the rate expression, it was proposed that coordinated water
€ lost a proton to give a hydroxy Pd-alkene intermediate.
HO
- Cl 2-
OH
H2O
PdCl42- + H2C=CH2 Cl Pd Cl Pd
- 2 Cl-, H+ Cl Cl
This process would proceed with retention of stereochemistry at the alkene carbons. In contrast,
if coordinated ethylene was attacked by an external nucleophile, the stereochemistry of the
carbon attacked by water would be inverted. Only in the late 70’s was the mechanistic question
resolved.
Internal Attack
O
HO H D CO HO O H
CO H H -LnPdH
LnPd D D
LnPd LnPd D
H O H
D H HO D
D H D
External attack
O H
H D CO H O
-OH H -LnPdH
D LnPd D D
LnPd LnPd
CO OH D O D
D H H HO H
D H
Bäckvall, J. Am. Chem. Soc., 1979, 101, 2411; Stille, J. Organomet. Chem., 1979, 169, 239
Kevin Shaughnessy
110
PdCl2
CuCl2 H
H D O2, CO O
D
D H H2O O D
H
The currently accepted mechanism involves external nucleophilic attack of water on a bound
alkene. The Pd species is actually an aquo complex, so there should be a [H2O]2 term in the rate
expression, but since water is the solvent it is not observed.
2- -
Cl Cl Cl Cl H2O H2O Cl
Pd Pd Pd
Cl Cl Cl- Cl Cl- Cl
H2O
-H+
1/2 O2
–
2 CuCl2
H2O Cl H2O Cl
Pd Pd
H Cl
O -Cl–
OH OH
H
+ HCl
It was originally assumed that vinyl alcohol was dissociated followed by tautomerization to
acetaldehyde. However, carrying out the reaction in D2O resulted in no deuterium incorporation
on the methyl group. Therefore, it was assumed that the coordinated vinyl alcohol underwent
insertion to give a secondary Pd-C bond. b-H elimination of the OH hydrogen then resulted in
formation of the aldehyde.
H2O Cl O
H2O Cl Pd
Pd + Pd-H
H H H
O
OH
A recent computational paper (J. Am. Chem. Soc. 2006, 128, 3132) shows that this b-H
elimination has a very high activation barrier (36 kcal/mol). This value is nearly double the 19.8
kcal/mole that has been measured for the overall Wacker cycle. Since this transition state was
unreasonable, they looked for lower energy ones. The one they identified involved a Cl mediated
proton abstraction. This transition state leads to the loss of both HCl and acetaldehyde from the
Pd center in the same step. As a result, this reaction can be considered more similar to a
heterolytic reductive elimination, rather than a b-H elimination.
Kevin Shaughnessy
111
TSE = 36.3 kcal/mole
H O
X H2O Pd
Cl O + Pd0
H2O Pd
OH H + HCl
Cl
H2O Pd
O
Cl
H
TSE = 18.7 kcal/mole
h3-Allylic substitution:
Nucleophilic attack on h3-allyl species, particularly those of palladium(II), are widely used to form
new C-C and C-heteroatom bonds. In many cases these reactions can be accomplished in high
enantioselectivity.
Nucleophilic attack on metal allyl complexes generally occurs at the terminus of the allyl unit,
often at the less-substituted end.
Ph Ph NaCH(CO2Et)2
Ph Ph
+ P(PPh3)4 + NaCl
Pd PPh3
Cl PPh3
EtO2C CO2Et
h3-Allyl species can be formed by allylic C-H activation, but the most common route to Pd-allyl
species is by oxidative addition of allylic halides or acetates. This reaction goes with clean
inversion. The regioisomeric allylic acetate gives the identical Pd-allyl. Soft nucleophiles (pKa <
25) attack the face opposite the metal center to give clean inversion. Therefore, the overall
reaction occurs with retention of stereochemistry. Attack generally comes at the less hindered
terminus of the allyl group. (J. Am. Chem. Soc. 1983, 105, 7767)
Kevin Shaughnessy
112
+
(dppe)Pd(0) Ph (dppe)Pd(0)
Ph Ph
Pd OAc
OAc Ph2P PPh2
58 % ee
47 % ee
CO2Et
CO2Et
Ph
EtO2C CO2Et
37 % ee
In contrast, hard nucleophiles (pKa > 25) tend to add to the metal first. Bond formation is by
reductive elimination, which occurs with retention. Therefore, the overall substitution reaction
occurs with inversion. (Chem. Comm. 1984, 107).
Ph Ph Ph
RMgX
Pd + Pd(0)
Pd R
R
Other polyene and polyenyl systems:
Other polyene and polyenyl systems undergo attack similarly to allyl systems. Attack is exclusively
from the face opposite the metal.
Nu
+
Nu-
Fe Fe
CO CO
OC CO OC CO
CH3
H -
MeLi
Cr Cr
CO CO
OC CO OC CO
Electrophilic Substitution and Abstraction
Electrophilic addition:
We have already discussed some examples of electrophilic addition reactions. Typically these
reactions require a relatively electron rich metal center to act as a base. The electrophile can
either add first to the metal center, or directly to the ligand. The order of addition will depend on
the relative basicity of the metal and the ligand.
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113
Cp' Cp' Cp'

HBF4 Co
Co Co
L H L
L
H
Cp Cp +
Fe CH3OTf
OC O Fe OMe
OC
OC OC
CH3 CH3
Other important examples of electrophilic addition include addition to electron rich metal allyls.
This provides a convenient synthesis of cationic metal olefin complexes. In this case, the allylic
group is introduced by an SN2 oxidative addition to Fp-.
Cp Cp +
HBF4
Fe Fe
OC OC
OC OC
Cp is usually not susceptible to nucleophilic attack, but electron rich metallocenes are prone to
electrophilic attack. Ferrocene undergoes electrophilic substitution reactions similar to benzene.
Depending on the electrophile, addition to a Cp ring of ferrocene can either occur directly or by
initial attack at iron. Mercuric acetate adds initially to the iron center followed by an endo attack
on the Cp ring. Exo deprotonation completes the electrophilic substitution. For a hard
electrophile, such as CH3CO+, exo attack on the Cp ring occurs directly. There is a strong
preference for exo deprotonation, so the proton is transferred to the other Cp ring followed by exo
deprotonation. This can be seen in the acetylation of d5-ferrocene.
Kevin Shaughnessy
114
H
+ + HgOAc
HgOAc
Hg(OAc)2 -OAc
Fe Fe HgOAc Fe Fe
+ HOAc
D COCH3 D +
D
D D COCH3
D D D +
CH3CO+ D D
D D Fe
Fe D D
Fe
D H
D COCH3
-H+ D D
Fe Organometallics, 1997, 16, 1114
Electrophilic abstraction of metal alkyls:
The most common electrophilic attack is by proton. Early transition metals are very reactive
towards even weak acids such as water, but later transition metals require more vigorous
conditions. For metals with d electrons, protonation at the metal followed by reductive elimination
is thought to occur. Since do metals cannot be protonated, attack must occur at the ligand.
dn Metal (n > 0) +
H +
H+ H
LnM CH3
LnM CH3 LnM LnM+ + CH4
CH3
d0 Metal
H+ H
+
LnM CH3 LnM LnM+ + CH4
CH3
In cases where attack at the metal center occurs first, we would expect to see retention of
configuration.
D +
DCl
Fe(CO)2Cp Fe(CO)2Cp
H3C H3C
D + ClFe(CO)2Cp J. Organomet. Chem. 1979, 182, C65

H3C
Kevin Shaughnessy
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8-Catalysis General Principles
One of the most important applications of organometallic compounds has been in catalysis, primarily
directed towards organic synthesis. Catalytic applications range from large scale industrial processes,
such as olefin polymerization, hydroformylation, and hydrogenation processes to complex transformations
used in academic synthesis and the pharmaceutical industry.
Catalysis Defined:
A catalyst is defined as a substance that increases the rate of a chemical reaction without being
consumed. This is achieved by lowering the activation barrier compared to the uncatalyzed reaction.
Note that the thermodynamics of the reaction are unaffected.
Typically, the catalyst (C) will first bind to the substrate (S) and then promote the reaction by a lower
barrier pathway, thus lowering ∆G‡ (ii). The catalyst will then release the product to restart the cycle. If
the substrate-catalyst complex is too stable, and the transition state energy not lowered enough, then
there is no catalysis. The barrier is actually higher (iii). If the C reagent is incorporated into the product,
or otherwise irreversibly altered, then it is not a catalyst (iv). In this case, C would be a reagent (if
incorporated) or would mediate the process if it is converted into a species that will not promote the
reaction, but is not part of the product.
i ii
∆G‡
∆G‡
S S+C
S-C
P P-C
P+C
iii Uncatalyed Catalyzed

iv
∆G‡ ∆G‡
S+C S+C
S-C
S-C P-C P-C
P+C
No Catalysis Mediated Process
Transition state not stabilized C incorporated in product
Enzymes catalyze reactions by binding the reactants in the proper orientation for the reaction and
stabilizing the transition state species. Organometallic complexes typically catalyze reactions by
providing alternate, lower energy pathways. Consider the reaction of aniline with bromobenzene. The
direct reaction will not occur, because there is no low energy pathway for this reaction. An SN2 reaction is
not possible because the back side of the C-Br is inaccessible. SNAr is unlikely because the carbanion
intermediate would be very unstable. A benzyne process is unlikely because aniline is not a strong base.
This reaction can be accomplished at low temperature using a palladium catalyst, however. In this case,
Kevin Shaughnessy
116
the C-Br bond is broken in an oxidative addition step, that occurs readily. The amine is then coordinated
to palladium, deprotonated, and then reductive elimination occurs (details in Chapter 8).
Br + H2N No Reaction
Pd 1. Oxidative addition
H 2. Ligand substitution
Br + H2N N 3. Reductive elimination
Classes of catalysts
One way that catalysts are classified is by whether they are in the same phase as the reagents or not.
Heterogeneous catalyst: A heterogeneous catalyst is not soluble in the reaction phase. Often the
catalyst is a solid and the reactants are liquids and/or gases. Heterogeneous catalysts are often metals
supported on a solid substrate, such as a metal oxide (alumina, silica) or carbon. These types of
catalysts are preferred for large scale industrial processes because product separation from the catalyst
is simple. There is often limited ability to rationally modify the catalyst species, which will often be a
distribution of metal particles.
Homogeneous catalyst: A homogeneous catalyst is by definition soluble in the reaction mixture. Most
typically it is a molecular organometallic complex, although soluble metal nanoparticles can also be
considered homogeneous. We will primarily focus on these types of processes. Because ligands are
involved, it is possible to infinitely tune the reactivity and selectivity of the metal center. The challenge
with these processes is separating the catalyst from the product. This is necessary to recover high value
metals and to avoid metal contamination products, such as drugs.
Asymmetric catalysts: A special case of catalysts that can convert achiral starting materials into a chiral
product. They are usually homogeneous catalysts, although some heterogeneous versions are known.
Typically, a chiral ligand is used to promote the asymmetric reaction. Asymmetric catalysis is very
important in modern organic chemistry as it allows a small amount of a chiral compound to produce large
amounts of chiral products from relatively cheap achiral starting materials.
The catalytic cycle
Catalytic mechanisms are typically written as a catalytic cycle to emphasize the fact that the catalyst
returns to a common active species. Note that the active species may not be the organometallic complex
that is put into the reaction. Often a precatalyst is used that is converted to the active species, which is
what actually catalyzes the reaction. In many cases the active catalyst is formed in situ by the processes
that could include: dissociation of ligands, coordination of new ligands, and/or oxidation or reduction of
the metal center. Reagents that enter the cycle and products or by products formed are shown as
entering or leaving the cycle. The metal complexes involved in the cycle are shown on the catalytic cycle.
Kevin Shaughnessy
117
MXo + nL LnMXo Ln+mMy L′nMy
-mL nL
activation
L n My S
P
L nM P L nM S Resting state/inactive species
Other reagents
L nM I
Resting state/inactive species
The productive steps on the catalytic cycle are the key to product formation. There may be processes
that take the catalyst out of the active cycle. These could be steps that revert the precatalyst to an
inactive form, such as ligand coordination. Alternatively, they could be steps that convert an intermediate
into a non-catalytic species either reversibly or irreversible. If irreversibly, then this is a catalyst
deactivation process. If reversibly, then this may be a resting state for the catalyst.
Catalyst resting state: The species at highest concentration during the catalytic cycle. Typically would be
the species prior to the rate limiting step of the catalytic cycle.
Rate limiting step: The slowest step in the catalytic cycle. Therefore, the step with the highest activation
barrier. Improving the rate of a catalytic reaction requires speeding up this step.
Quantifying the efficiency of a catalytic reaction
Typically organic chemists define reaction efficiency as the yield of a chemical process. This is not very
informative, as it does not indicate anything about the rate of a process. Only how much product is
formed at some indeterminate time. For catalytic systems there are a number of metrics that provide
information on how efficient the catalyst is.
Turnover number (TON): This is simply the number of moles of product formed divided by the moles of
catalyst used (mol/mol cat). There is no time component to this value, so it does not indicate rate. It is an
indication of the stability of the catalyst. A higher TON means the catalyst can survive for a long time,
relative to the reaction rate. For industrial processes, a TON of 1000 is typically a minimally acceptable
value for high value products, such as pharmaceuticals. The goal is to have this value as high as
possible. Catalysts with TON in the 104-6 range are common.
Turnover frequency (TOF): The turnover frequency is the TON divided by time (mol/mol cat•time). The
time unit can be in seconds, minute, or hours. For reactions involving gases, there may also be a
pressure term associated (mol/mol cat•h•bar). This value provides kinetic information about a reaction.
To get true kinetics, the TOF would need to be measured as a function of time.
Kevin Shaughnessy
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Chiral Catalysis
An asymmetric catalyst typically has a chiral ligand environment. A common situation is that the chiral
catalyst will bind selectively to one face of a prochiral compound, such as an alkene. This is controlled
through steric interactions most commonly. Since the catalyst is chiral, it forms diastereotopic complexes
with a prochiral substrate. The enantioselectivity of the catalyst will be determined by the energy difference
between these two diastereotopic intermediates. The energy difference required is relatively small. A 1.37
kcal/mol difference in energy (assuming room temperature) results in a 9:1 selectivity. A 99:1 selectivity is
achieved with a 2.74 kcal/mol difference.
si-S-C*
∆∆G
P M P
re-S-C*
S + C*
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9 Cross-Coupling Reactions
Over the past 20-30 years an extensive collection of metal catalyzed cross-coupling reactions of organic
halides and nucleophiles has been developed. These reactions have become powerful synthetic
methods because they allow C-C and C-heteroatom bonds to be formed under very mild conditions with
excellent functional group tolerance. Their influence was recognized with the 2010 Nobel Prize, which
went to Richard Heck, Akira Suzuki, and Ei-ichi Negishi for their role in the development of these
reactions.
Coupling with organometallic reagents

RM
R'MgX - Kumada
Pd R'ZnX - Negishi
Ligand R'Zr - Negishi
Base R'BX2 - Suzuki-Miyaura
Br + RM R
RSi(OR)3 - Hiyama, Denmark
R'SnR"3 - Stille
R Cu - Sonogarshira
Hartwig-Buchwald heteroatom cross-couplings
Pd
Ligand
Base HER = amine, amide, thiol, ether,
Br + HER ER ketone, etc.
Heck Coupling
Pd
H R' Ligand R
Base
Br +
R R" R"
R'
With the exception of the Heck reaction, all of these coupling reactions follow the same general catalytic
cycle: 1) oxidative addition of the organic halide; 2) ligand substitution of the nucleophile for the halide; 3)
reductive elimination of the new organic product.
RBr MN+2
Br
Nu
Oxidative R'MgX - Kumada
addition R'ZnX - Negishi
Nu R'Zr - Negishi
Ligand R'BX2 - Suzuki-Miyaura
Mn Substitution RSi(OR)3 - Hiyama, Denmark
R'SnR"3 - Stille
R Cu - Sonogarshira
R2NH - Buchwald-Hartwig
Reductive
Elimination ROH - Buchwald-Hartwig
RSH - Buchwald-Hartwig
R enolate - Buchwald-Hartwig
R-Nu
MN+2
Nu
Kevin Shaughnessy
120
The Heck reaction follows a similar mechanism that we will focus on later, which involves: 1) oxidative
addition; 2) ligand substitution by the alkene; 3) migratory insertion; 4) ß-hydride elimination; 5) reductive
elimination.
General Trends in Pd-Catalyzed Cross-Coupling: Apply with minor variations to all cross-coupling
reactions
1. Catalyst Precursors:
Metal Sources: Palladium is the most widely used metal for cross-coupling followed by copper, although
there are examples of nickel, cobalt, rhodium, and iron(?) catalyzed coupling reactions as well. Generally
the palladium is supported by a ligand. The catalyst can be derived from a preformed complex (i.e.,
(Ph3P)4Pd, (Ph3P)2PdCl2, etc.) or formed in situ from combinations of Pd sources (PdCl2, Pd(OAc)2,
Pd(dba)2, etc) and a ligand. Both Pd(0) and Pd(II) sources can be used, although the active species is
Pd(0) in all cases.
Pd0 PdII
(Ph3P)4Pd (Ph3P)2PdCl2
O
O Pd(OAc)2
Ph
Ph
Pd2(dba)3
Pd(dba)2 Pd
Pd PdCl2
Ph Ph
Ph
Ph
(CH3CN)2PdCl2
O
Pd/C
Nickel can catalyze many of the same reactions as palladium. Nickel is attractive because it is much less
expensive than palladium. Nickel-based catalysts tend to be less active and general, however. Nickel is
better at activating aryl chlorides and C-O bonds than palladium, however. Platinum has shown no
activity in cross-coupling chemistry. Copper(I) is also a useful catalyst for cross-coupling. In fact, copper-
promoted systems developed by Ullmann and Goldberg in the early 1900s were the first examples of
metal-catalyzed cross-coupling.
Ligands: Palladium alone can catalyze cross-coupling reactions without additional supporting ligands,
but usually only with reactive substrates (ArI) and/or high temperatures. Ligands are usually necessary to
give more active catalyst systems. The ligand serves to stabilize the Pd0 intermediate, solubilize the
catalyst, and increase the rate of oxidative addition.
Phosphines: Phosphines remain the most widely used ligands. The most commonly used phosphine is
triphenylphosphine. In general, arylphosphines remain the most widely used. Monodentate phosphines
are usually the most effective ligands, but some chelating ligands like dppf and binap have proven useful
in certain reactions.
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121
CH3
PPh2
PPh2
P P Fe
PPh2
3 3 PPh2
dppf
BINAP
Sterically demanding, electron rich phosphines have received increasing attention recently as they
provide more effective catalysts for less reactive substrates, such as aryl chlorides. The key features of
these ligands is that their steric bulk promotes low coordination LPd(0) complexes and their strong
electron-donating ability makes the palladium highly reactive towards oxidative addition.
P PR2 PtBu2
3
P Bu MeO OMe Fe PCy2
2 R = Cy, t-Bu
G. C. Fu M. Beller S-Phos Josiphos

J. F. Hartwig S. L. Buchwald J. F. Hartwig
The Buchwald ligands, such S-Phos, have been designed to provide high catalyst activity (Angew. Chem.
Int. Ed. 2008, 47, 6338). The biaryl structure stabilizes the monodentate Pd(0) species through
coordination to the second aromatic ring. Substituents on the ortho position prevent cyclometallation.
Additional substituents ortho to the phosphine favor the conformation in which the palladium is oriented
over the bottom aryl ring.
Ar
Cy Cy
Cy Cy
H3CO Pd Pd H3CO Pd Pd X
iPr iPr
ArX
Forces Pd to be
over aryl ring
iPr iPr
Prevent cyclometallation
Favor perpendicular ring orientation
Aryl ring stabilizes Pd
Promotes reductive elimination
N-Heterocyclic Carbenes: N-heterocyclic carbenes (NHCs, Arduengo carbenes) have attracted

significant attention as ligands for cross-coupling reactions. NHCs are stronger electron donors than
phosphines and they tend to have stronger M-L bonds, thus they may give more stable catalysts. Major
players in the application of carbene ligands to cross-coupling are Wolfgang Herrmann, Steve Nolan, and
John Hartwig
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122
CH3 CH3
i-Pr H3C i-Pr

H3C
i-Pr CH3 i-Pr
CH3 N N N
N
N N N
N CH3 i-Pr
CH3 i-Pr
i-Pr H3C i-Pr
H3C
CH3 CH3
IMes IPr sIMes sIPr

2. Generation of Catalytically Active Species
In almost every case, the metal/ligand combination added to the reaction is not the true catalytically active
species. (Ph3P)4Pd may be the closest example of the active catalyst resembling what was added to the
reaction, although two phosphines must dissociate to give the true active species. Many catalysts are
generated in situ from a Pd source and an appropriate ligand. At a minimum, a ligand exchange must
occur for the desired ligand to coordinate to the Pd(0) precatalyst. If a Pd(II) source is used, then there
must be some mechanism for the Pd(II) precursor to be reduced. In many cases, it has been shown that
the presumed catalyst actually decomposes to highly active palladium colloids, which are the true active
catalysts.
Ligand Substitution: Catalysts derived from Pd(dba)2.
Pd(dba)2 (Pd2(dba)3 and Pd2(dba)3·CHCl3 serve the same purpose) is the most common Pd(0) catalyst
precursor. The dba ligands can be easily displaced with phosphines to give Pd(0)-phosphine complexes.
The dba ligand is not completely uninvolved, however. When 2 equivalents of P/Pd are used, mixed
phosphine/dba complexes are formed. The dba acts as a weakly coordinating ligand that can be
displaced by ArX.
-dba Ph3P xs PPh3

Pd(dba)2 + 2 PPh3 Pd Ph Pd(PPh3)n
-dba
Ph3P Ph n = 2-4
equilibrium
mixture
O
1 P-P P P
Pd(dba)2 + P P 1/2 Pd P + 1/2 Pd(dba)2
fast Pd Ph
dppf or P P
binap P Ph
2 eq P-P P-P = dppf L = binap
C. Amatore and A. Jutand, Coord. Chem. Rev. 1998, 178-180, 511-528.
Preferred Ligand:Pd ratios: Depending on the size of the ligand, there will be a preferred ligand to Pd
ratio for the stable homoleptic ligand (phosphine or carbene) complex. The true active species will have a
lower coordination number due to the need for an open site for oxidative addition to occur (Notes,
Kevin Shaughnessy
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Chapter 4.2). Chelating diphosphines will generally behave like small phosphines as in the Amatore
example above.
Small R3P Large R3P IMes, IPr, etc.

(q < 170, i.e. PPh3) (q > 180, i.e. Pt-Bu3)
Stable LnPd(0) L4Pd L2Pd L2Pd
LnPd(dba) L2Pd(dba) LPd(dba) LPd(dba)
Active species L2Pd LPd LPd
Reduction of Pd(II) to Pd(0): Pd(II) sources are popular as they are less expensive than Pd(dba)2.
There are several mechanisms by which the Pd(II) precursor can be reduced under the reaction
conditions.
Reduction by an organometallic species: The organometallic coupling partner can reduce the Pd(II)
precursor by displacing the two anionic ligands to give a PdR2 complex that undergoes reductive
elimination. This is the major mechanism of reduction for couplings involving organometallic
nucleophiles.
LnPdX2 + 2 RM LnPdR2 L2Pd0 + R-R

- 2 MX
Reduction by an amine or alcohol: Amines or alcohols with b-hydrogens can coordinate to Pd(II) centers
and then undergo b-hydrogen elimination. Deprotonation of the Pd(II)-hydride (reductive elimination)
gives the Pd(0) active species. This reduction pathway is most important in Heck and Hartwig-Buchwald
couplings.
L H L
LnPdX2 + Et3N Cl Pd NEt2 + Cl Pd H

N
Et Et
L L
Et3N
L2Pd(0) or [L2Pd-Cl]- + Et3NH+l
Reductive elimination of P-O: Triarylphosphines can reduce Pd(II) species in the presence of hard
oxygen anions, such as acetate or hydroxide. The reduction involves reductive elimination of a P-O
species. Jutand and Amatore have shown that Pd(OAc)2 is reduced by PPh3 to give anionic Pd(0)-
acetate complexes, which appear to be the true active species. The P-O species ultimately ends up as a
phosphine-oxide. (C Amatore and A. Jutand, Acc. Chem. Res. 2000, 33, 314-321).
PPh3
-
PPh3
AcO Pd OAc Ph3POAc + [(PPh3)Pd(OAc)] [(Ph3P)3Pd(OAc)]-
PPh3 AcO-
H2O
Ph3PO + HOAc Ph3PO + Ac2O
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124
Generation of Pd(0) colloids or nanoparticles: "Ligand free" catalyst systems are believed to be
catalyzed by soluble Pd(0) clusters. These clusters can be highly active, but tend to grow until they
precipitate as unreactive Pd metal precipitate (Pd black). Halide salts, surfactants, polymers, and other
weakly coordinating ligands have been shown to stabilize these nanoparticles. The formation of insoluble
Pd particles is also the main deactivation mechanism for ligand supported catalyst systems.
X-
Reduction X- X- combination
PdXn Insoluble cluster
X- X-
X-
Active soluble
nanoparticle
Heterogeneous catalysts: There has been some work on the use of heterogeneous palladium sources.
The most common is Pd/C. Often these heterogeneous catalysts leach soluble nanoparticles into
solution that do the catalysis. If the particles redeposit on the support in a usable form, the catalyst can
be recycled. Review: Chem. Rev. 2018, 118, 2249
Generation of LPd(0) from precatalyst species
Most cross coupling reactions are performed by the in situ generation of the active catalyst from a ligand
and a palladium precursor. There is growing interest in the development of stable palladium-ligand
complexes that will readily form the active species under the reaction conditions. In particular, systems
that will generate an LPd(0) species rapidly from a stable precursor are desired (Isr. J. Chem. 2019,
online, DOI: 10.1002/ijch.201900067)
Palladium-allyl complexes: Allyl palladium phosphine and carbene complexes are effective sources of
LPd(0) active species (Acc. Chem. Res. 2008, 41, 1440; J. Org. Chem. 2010, 75, 6477). The mechanism
of activation involves nucleophilic attack on the allyl, resulting in reductive elimination to give a LPd(0)
active species. Unsubstituted allyl complexes are prone to formation of dipalladium(I) µ-allyl dimers that
are catalytically inactive. This process occurs thermally upon storage and more rapidly during activation.
This problem can be reduced by using the cinnamyl complex. An indenyl complex reported by Hazari
completely avoids the Pd(I) dimer formation.
Kevin Shaughnessy
125
H H H
H H H H H Ph tBu
H H H H H H
R
N Pd Pd Pd
Cl R 3P Cl Pd
L Cl L Cl
NR
Nolan Shaughnessy Nolan Hazari
Colacot Colacot
H
H
H H
H H O tBu H H
H H OtBu + Cl–
Pd L Pd +
L Cl Pd Reductive
L Ot-Bu Elimination
H
H H
H H
L Pd + Pd Pd catalytically inactive
Pd L L
L Cl Cl
PEPPSI Catalysts: Prof. Michael Organ at York University in Canada has developed what he calls the
PEPPSI family of catalysts (PEPPSI = pyridine-enhanced precatalyst preparation, stabilization, and
initiation) (Org. Proc. Res. Dev. 2014, 18, 180). The PEPPSI catalysts have a single NHC carbene ligand
and a labile 3-chloropyridine ligand. The chloropyridine ligand can be readily displaced to give the low-
valent Pd(0) complex, but can recoordinate to stabilize the Pd(0) active species allowing for long catalyst
lifetimes. The complex is a Pd(II) species, so must still undergo reduction to Pd(0) under the reaction
conditions.
Et Cl Cl Et Cl Cl
Et Et Cl Cl
N N N N
N N Ar
Ar Ar Ar
Reduction
Cl Pd Cl Pd
Pd
Et Et Et Et
N +
N
N
Cl
Cl
Pd-PEPPSI-IPentCl Cl
Buchwald Palladacycles: Buchwald has developed air-stable palladacycle complexes that undergo rapid
reductive elimination to form nitrogen heterocycles and LPd(0) active species (Chem. Sci, 2013, 4, 916; J.
Am. Chem. Soc., 2008, 130, 6886). The ligands in these complexes are typically 2-biarylphosphines (i.e.
S-phos) developed by Buchwald.
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126
Synthesis
Cl
Me2
N CH3
NH2
Pd L
N CH3 L Pd Gen1
Me2
NH2Cl
L = phosphine, NHC
NH3 Pd(OAc)2 NH2 2 L NH2

Pd Gen2: X = Cl
Pd L Gen3: X = OMs
X– X 2 X
Activation
H
L N
+ LPd(0) + Cl–
Pd
NH2Cl NaOtBu
H
N
+ LPd(0) + –OMs
NH2
Pd L
OMs
3. Oxidative Addition:
Oxidative addition is the rate limiting step in many cross-coupling reactions, particularly with less reactive
bromide and chloride substrates.
All classes of organic halides have been successfully used in cross-coupling reactions, although sp2-
organohalides are the most commonly used substrates. In addition, a variety of other leaving groups,
such as triflates, tosylates, diazonium ions, phenyl iodonium ions, etc. have been explored in these
reactions. Halides remain the most common class of substrate.
General reactivity trends

Aryl Halides: As discussed in chapter 4, the rate of oxidative addition is: ArI > ArBr > ArCl. Aryl
triflates generally fall between iodides and bromides. Tosylates and mesylates are generally similar
to chlorides, but not all catalyst systems are effective for sulfonate leaving groups. Electron-
withdrawing groups make the aryl halide more reactive, while electron-donating groups deactivate the
aryl halide.
Ligand Choice: Although the exact conditions will depend on the substrates, ligand structure, and
other reaction conditions, a general idea of the ability of various catalyst types to couple aryl halides
is shown below. Activated (EWG) aryl halides will be at the low temperature end, while deactivated
(EDG) aryl halides will be at the high end, or possibly completely unreactive.
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127
ArI ArBr ArCl

Ligand Free, N, O, and rt – 80 °C 80 – 150 °C usually not possible
S ligands
Triarylphosphines room temp 50 – 120 °C >150 °C, if at all
Trialkylphosphines and room temp, very fast room temp room temp – 100 °C
NHCs
Bulky alkylphosphines give stable 3-coordinate species, rather than either 4-coordinate L2Pd(Ar)X
(PPh3) or dimeric [LPd(Ar)X]2 complexes (P(o-tol)3) (Hartwig, JACS, 2004, 126, 1184-1194)). In the
presence of an excess of bulky alkylphosphine, the aryl halide complex reductively eliminates Ar-X
(Hartwig, Organometallics, 2004, 23, 1533-1541).
With bulky alkylphosphines, the mechanism of oxidative addition to L2Pd is different, depending on the
halide (Notes, Chapter 4.2; Hartwig, JACS, 2009, 127, 8141-8154).
• ArI: rate limiting associative substitution of ArI for L followed by fast oxidative addition.
• ArBr: rate limiting dissociation of phosphine, followed by fast oxidative addition to LPd
• ArCl: reversible dissociation of phosphine, followed by rate limiting oxidative addition to LPd
Alkenyl Halides: Alkenyl halides have similar reactivity trends to aryl halides. Oxidative
addition/reductive elimination almost always occurs with retention of olefin geometry.
Alkyl Halides: As discussed in chapter 4, alkyl halides oxidatively add by SN2 or radical
mechanisms. Benzyl and allyl halides are the most reactive (SN2). Simple alkyl halides typically
undergo oxidative addition slowly (mostly radical). Reductive elimination is also slow, generally If ß-
H are present, elimination is usually an important side reaction. Generally alkyl halides are not good
substrates for cross-coupling.
Slow Br Fast X
LnPd + Br R LnPd LnPd + R
H H
Radical mechanisms may also be R
involved
Nu
Nu
LnPd R + LnPd
H Nu
Slow
R
Greg Fu (MIT) has shown examples of Suzuki, Sonogashira, and Stille couplings of alkyl halides can
be achieved by proper choice of ligand (J. Am. Chem. Soc. 2003, 125, 13632; ibid, 3718; Angew.
Chem. Int. Ed. 2002, 41, 1945, J. Am. Chem. Soc., 2001, 123, 10099, review Science, 2017, 356,
eaaf7230).
Kevin Shaughnessy
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The reactions are typically limited to primary and secondary alkyl halides. Some examples of tertiary
halides have been reported (ACS Cent. Sci, 2016, 2, 647). Alkyl-alkyl couplings are largely limited to
coupling of alkyl halides with Grignard reagents, organoboron, and organozinc compounds.
4. Reductive Elimination: Reductive elimination is usually a fast step in the catalytic cycle, so there is
less focus on designing ligands to promote it. Reductive elimination is favored by electron deficient
ligands (opposite of oxidative addition) and sterically demanding ligands (same as oxidative addition).
Occurs only from cis LnPdRR'
aryl-aryl ≈ vinyl-vinyl/aryl > alkyl-aryl/vinyl > alkyl-alkyl > Me-Me
For (Ph3P)2PdMe2, rate of R.E. is µ to 1/[PPh3] LnPd
For (Ph3P)2PdPh2, R.E. occurs directly from the 4-coordinate species.
Miyaura-Suzuki Coupling
The Suzuki coupling involves the cross-coupling of an organohalide and an organoboron species. This
reaction is widely used in organic synthesis because organoboron compounds are generally air and water
stable and the products are non-toxic (borax). For reviews see: Chem. Rev. 1995, 95, 2457; J.
Organomet. Chem. 1999, 576, 147; Chem. Commun. 2005, 4759. This methodology is widely used and
has been incorporated into a large number of industrial scale syntheses, particularly in the
pharmaceutical industry.
Pd(PPh3)4
H 3C Br + (HO)2B H 3C + B(OH)3 + NaBr +
aq Na2CO3 NaHCO3
benzene
reflux
F
Cl
N OH OH
SO2Me
Bu OH CO2–
N N N
Cl
N NK
0.5Ca2+
N N
N
Etoricoxib Losartan Pitavastatin
Arcoxia Cosaar Livalo
pain and inflamation anti-hypertensive high cholesterol treatment
General Features
• RX: The organic halide can be aryl, alkenyl, alkyl. The leaving group is typically a halide (I, Br,
Cl), but examples with sulfonates are also known.
• Organoboron: Boronic acids are most common followed by trifluoroborates. Boronate esters,
triorganoboron, and tetraorganoborate nucleophiles are also used. The R group on boron can be
sp, sp2, or sp3.
Kevin Shaughnessy
129
O
RB(OH)2 R B RBF3– R B NaBPh4
O
boronic acid boronate ester trifluoroborate triorganoboron tetraorganoborate

• Base: The reaction requires a base. The most common base is aqueous sodium carbonate.
Anhydrous conditions are also common using heterogeneous bases, such as CsOH, Na2CO3, or
K3PO4.
• Organic solvent: Organic cosolvents can range widely. Most common are relatively non-polar
solvents, such as toluene or THF. Aqueous conditions are also commonly done with ethanol or
acetone as the organic cosolvent.
Catalytic Cycle:
Triphenylphosphine:
L 4Pd
L = PPh 3
-2L
R1 X
L Pd L
R 2 R1
Reductive Oxidative
Elimination Addition
L L
R 2 Pd R1 X Pd R1 via cis
L L
Ligand Substitution
Transmetallation
MOH
B(OH) 3 L
MOH HO Pd R1 MX
ArB(OH)3 M R 2B(OH) 2
L
Transmetallation: Organoboranes or boronates are only weakly nucleophilic, which is why they are
stable to water and oxygen (organoboronates, boronic acids only). This low nucleophilicity means
that they do not undergo transmetallation with palladium halides, except in the presence of oxygen or
fluoride Lewis bases. Therefore, typical Suzuki coupling conditions either involve aqueous hydroxide
or fluoride salts in organic solvents.
Kevin Shaughnessy
130
Ph3P I RB(OH)2
Pd No reaction
Ph PPh3
Ph3P I RB(OH)2 Ph3P R

Pd Pd Ph-R + (Ph3P)2Pd
Ph PPh3 base Ph PPh3
(Na2CO3, NaOH, CsF, etc)
One explanation for the base accelerating effect is that tetrahedral boron-ate complexes are formed.
LB
R-BX2 + LB:- stronger nucleophile
B
X
R X
In fact it has been shown that in the presence of hydroxide or fluoride, that boronate species are
formed from boronic acids typically used in the Suzuki coupling.
-OH
ArB(OH)2 ArB(OH)3- J. Am. Chem. Soc., 1995, 117, 1479
pH > 11
CsF
ArBF3- J. Org. Chem., 1994, 59, 5034
The other possible role for hydroxide is formation of a Pd-hydroxide complex. Results by Jutand and
Amatore show that Pd-hydroxide complexes play a key role in the Suzuki coupling and that
trihydroxyborate salts are not reactive (Chem. Eur. J., 2011, 17, 2492-2503).
PPh3 –OH PPh3 Ph B(OH)2 PPh3

Ar Pd X Ar Pd O Ar Pd Ph + B(OH)3
H
PPh3 PPh3 PPh3
PhB(OH)3–
PhB(OH)2
PPh3
Ar Pd Ph
PPh3
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131
Other Organometallic Cross-Couplings: A wide range of organometallic species can be used in

cross-couplings that are analogous to the Suzuki coupling. The most common examples include:
RLi, RMgX (Kumada), RSi(OR)3 (Hiyama-Denmark), RSnBu3 (Stille), RZnX (Negishi). In principle,
any metal that is more electropositive than palladium will undergo transmetalation, and thus can be
used in a cross-coupling reaction. The list includes all main group metals and metalloids, as well as
many transition metals. The choice of reagent primarily comes down to what type of organometallic
species can be most readily accessed.
Sonogashira Coupling
The Sonogashira coupling involves the arylation of a terminal alkyne. Copper is often used as a co-
catalyst to promote the formation of a copper acetylide in these reactions. Heck and others had reported
the palladium catalyzed coupling of aryl halides and alkynes (J. Organomet. Chem. 1975, 93, 259).
Sonogashira reported that catalytic Cu(I) salts accelerated the reaction and improved yields (Tetrahedron
Lett. 1975, 16, 4467). Review (Chem. Rev. 2007, 107, 874).
Ph
(Ph3P)2PdCl2 (5 mol %)
I CuI (10 mol %)
+ Ph
90%
Et2NH, rt
General features:
• Organic halide: Aryl and alkenyl halides are most common. Examples with alkynyl halides are
known. Alkyl halides (1°) don't require a catalyst. The halide can be I, Br, Cl, OTf, OTs with
similar activity trends to the Suzuki coupling.
• Alkyne: Typically terminal alkynes. Examples with protected terminal alkynes, such as silyl
alkynes or propiolic acids (RCCCO2H) are also known.
• Catalyst: Earlier examples generally used triphenyl phosphine complexes. Modern versions use
bulky alkylphosphines, such as P(t-Bu)3. Wide range of ligands are useful. Unlike Suzuki
coupling, palladium chloride precursors tend to work best. CuI is typically used as the copper
source. Copper-free systems are known (see below).
• Base: The reaction requires a base. Most commonly this is an alkyl amine base, which may also
be the solvent. Examples with hydroxide or other oxygen bases are known.
• Solvent: Often the amine base. If not, it is typically a polar aprotic solvent, such as DMF.
Mechanism:
The mechanism follows the same general sequence as other cross-couplings. Oxidative addition is
followed by transmetalation from a copper-acetylide. The resulting complex undergoes reductive
elimination. There is also a copper catalytic cycle in which the copper coordinates the alkyne, which is
deprotonated to give the copper acetylide. A downside of the addition of copper, is that it can also
promote the homocoupling of the alkyne to give a conjugated diyne and Cu0. If there is trace oxygen, the
Cu0 can be recycled to CuI.
Kevin Shaughnessy
132
+ 2 CuCl
R' RX
0.5 R' R' + Cuo
2 Cu R
LnPd Glaser coupling
X
R' Cu
R' R'
R3NHX
LnPdCl2 Ln Pd0
R' H
CuX R”3N
R
R' R LnPd
R'
Because of the potential for Glaser coupling, copper-free catalyst systems have been sought. These are
generally possible with appropriate choice of base and ligand. For example, a P(t-Bu)3 catalyst system
using either piperidine or DABCO effectively couples aryl bromides and alkynes without copper. In this
case, the alkyne is thought to coordinate to the palladium, increasing its pKa, so that it can be
deprotonated. Example (Org. Lett. 2003, 5, 4191).
[(allyl)PdCl)]2 (2.5 mol %)

Br P(t-Bu)3 (10 mol %)
S + Ph Ph
DABCO S
acetonitrile, rt
Ar
t-Bu3P Pd Br H R
ArBr
Pt-Bu3
Cl DABCO Ar
0.5 Pd Pd t-Bu3P Pd t-Bu3P Pd Br
Cl
H R
R 3N
Ar R
Ar R3NHBr
t-Bu3P Pd R
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133
Buchwald-Hartwig Amination (and other couplings to moderately acidic nucleophiles)
Beginning in the 90's, John Hartwig (Yale) and Stephen Buchwald (MIT) independently developed
catalyst systems that promote the cross-coupling of aryl halides and amines to give aryl amines. This
methodology has become widely used because there were few mild methods to prepare aryl amines.
For reviews of this methodology, see: Buchwald et al, Acc. Chem. Res., 1998, 31, 805-818; Hartwig, Acc.
Chem. Res., 1998, 31, 852-860; Hartwig, Angew. Chem. Int. Ed., 1998, 37, 2046-2067, Hartwig, Acc.
Chem. Res. 2008, 41, 1534, Buchwald, et al, Chem. Sci, 2011, 2, 27.
In 1983, Kosugi showed that palladium could catalyze the amination of aryl halides with stannyl amines.
Pd cat.
Br + Et2NSnBu3 NEt2 + BrSnBu3
Chem. Lett., 1983, 927-928
Although synthetically unattractive, it represented a useful transformation that appears to proceed through
an unusual C-N reductive elimination.
Hartwig showed that in the presence of base, bound amines could be deprotonated to Pd-amide
complexes. These would undergo fast reductive elimination for C-N bonds.
P(o-tol)3 NHR2
R2NH
((o-tol)3P)2Pd + ArBr Pd Br Pd
Br
P(o-tol)3
2
LiN((SiMe3)2 P(o-tol)3
R2N Pd NR2 + (o-tol3P)2Pd
25 °C fast
(o-tol)3P
This mechanistic work showed the viability of using strong base to promote the coupling of amines and
aryl bromides. The Hartwig and Buchwald groups published this catalytic result nearly simultaneously.
Pd source
P(o-tol)3
base
Br + HNR2 NR2
base = KN(SiMe3)2
or NaOt-Bu
Hartwig, Tetrahedron Lett. 1995, 36, 3609
Buchwald, Angew. Chem. Int. Ed. 1995, 34, 1348
Based on a series of detailed mechanistic studies, it is possible to propose a mechanism in which all of
the steps are supported experimentally. For review see: Angew. Chem. Int. Ed., 1998, 37, 2046-2067.
Kevin Shaughnessy
134
L2Pd L = P(o-tol)3
Ar-H +L -L
ArX
LPd
R= 1˚ ArNR2 L X Ar
Ar Ar
alkyl Ar
Pd Pd
L Pd H L Pd NR2 L Pd X Ar X L
R
N
NHR2 R2NH
R'
X Pd Ar
HB MB L
MX
Supporting mechanistic data:
• Oxidative Addition: Inverse [P(o-tol)3] dependence, formation of dimer product

• Ligand substitution: Pd dimer readily split by amines to give square planar amine complex
• Deprotonation/Reductive elimination: Treatment of amine complex with base leads to rapid
reductive elimination, presumably through 3 coordinate species.
• ß-H elimination: When amines with primary alkyl substituents are used, arene formation
becomes a major side process.
Problems with this system:

• Required high temperatures (80-100 ˚C for aryl bromides)
• Secondary amines gave good yields, but primary amines gave low yields in most cases.
• Acyclic secondary alkyl amines often gave reduction of aryl halides.
b-Hydride elimination is facile in the three-coordinate intermediate prior to reductive elimination. Both
Hartwig and Buchwald reasoned that a chelating phosphine, which would necessarily give a 4-coordinate
species at this point, would hinder b-hydride elimination, since there would be no open coordination site
for the hydride (we will discuss this in the migratory insertion/reductive elimination chapter).
PPh2
PPh2 Fe
PPh2
PPh2
BINAP DPPF
Buchwald Hartwig
JACS, 1996, 118, 7215 JACS, 1996, 118, 7217
Kevin Shaughnessy
135
The mechanism for the chelating case has also been studied in some detail by Hartwig (JACS, 2000,
122, 4618-4630). The mechanism is similar to that proposed for the monophosphine. The main
differences are that oxidative addition gives a 4-coordinate species. In addition, the coordinatively
saturated species is part of the catalytic cycle, unlike in the P(o-tol)3 case. In the case of binap, ligand
dissociation is the rate limiting step. For dppf, ligand dissociation is reversible. Hartwig could not
determine whether ligand dissociation or oxidative addition was the rate limiting step for dppf.
Ar-NR2
P
P
Pd
P P
P P
reversible rds for binap
P for dppf P
P Ar
P
Pd N
RR Pd
P
P P
= DPPF or BINAP
P
Ar-X
P Ar P Ar
Pd Pd
ß-H elimination X
P NR2 P X
R2NH + NaOt-Bu
NaX + HOt-Bu
The next generation of ligands focused on sterically demanding alkylphosphines. Hartwig has applied
sterically demanding alkylphoshines (t-Bu3P, (1-adamantyl)2Pdt-Bu) and N-heterocyclic carbenes.
Buchwald has developed a family of 2-phosphinobiphenyl ligands. Catalysts derived from these ligands
promote amination of aryl bromides at room temperature and were the first systems to couple aryl
chlorides with amines.
i-Pr
PAd2 i-Pr
PCy2 PCy2 N
P P
N Fe Pt-Bu2
3
MeO OMe N
3
O i-Pr
i-Pr
SPhos Mor-DalPhos JosiPhos sIPr
The mechanistic details have not been fully worked out for these catalyst systems, but are likely similar to
the catalytic cycle for P(o-tol)3. Based on Hartwig's work with aryl halide oxidative addition, the rate
limiting step is likely ligand dissociation for coupling of aryl bromides and oxidative addition for coupling of
aryl chlorides.
Kevin Shaughnessy
136
General reaction features:

• RX: Aryl halides are most common, triflates and tosylates can be used in some cases. Vinyl
halides also work to give enamine products.
• Nitrogen nucleophile: Aryl amines work best, but primary and secondary alkyl amines can be
good substrates. Ammonia is a challenging substrate, but JosiPhos and some other ligand
classes work well. More acidic nitrogen compounds, such as azoles and amides have also been
successfully arylated. Examples with nearly all N-H bond systems are known.
• Ligand: Most active ligands are those listed above including bulky trialkylphosphines, 2-
phosphinobiaryls, and NHC ligands. The JosiPhos family are useful for ammonia. Chelating
ligands are effective for primary alkyl amines.
Related classes of reactions:
N-heterocycle arylation
O
O N
O N
N O
N
Pd2(dba)3 N
N XPhos H O
N H O
O H Br N
K3PO4 O H N
HN
toluene, 90 °C
N
Boc N 79%
Boc
Etherification
Ph
Cl O
[Pd(cinnamyl)Cl]2 (0.5 mol %)
JosiPhos (1.5 mol %)
Ph
HO Cs2CO3, toluene, 90 °C
N N
Sulfination
OMe OMe
Pd-PEPPSI-IPent (2 mol %)
Br LiOiPr (20 mol %) St-Bu
HSt-Bu
KOt-Bu, toluene, rt
Kevin Shaughnessy
137
Phosphination
OMe OMe BH3

BH3
Br Pd(PPh3)4 P Ph
P Ph
H K2CO3, MeCN OMen
OMen 82%
Cyanation
Pd2(dba)3
Br P(t-Bu)3 CN
+ NaCN
Zn dust
Me2N acetonitrile Me2N
70 °C
α-Arylation
Pd(OAc)2 (2.5 mol %) CF3
F3C Br O L (5 mol %) L=
LiOt-Bu O
NEt2 N
toluene, 110 °C PCy2
NEt2
Heck Coupling
The Heck coupling was one of the first Pd-catalyzed cross-coupling reactions to be developed. It still
remains widely used and studied. Although similar to the coupling reactions we have discussed, the
Heck reaction is unique, in that the C-C bond forming reaction is a migratory insertion, not a reductive
elimination. For reviews on the Heck reaction see: Heck, R. F, Acc. Chem. Res. 1979, 12, 146; Angew.
Chem. Int. Ed., 1995, 33, 2379; Chem. Rev. 2000, 100, 3009 (excellent discussion of the mechanism).
General features:
• RX: Usually an aryl or alkenyl halide. Alkyl halides have also been reported (Chem. Commun.
2014, 50, 3725).
• Alkene: Generally works best with conjugated, electron deficient alkenes such as styrenes or
unsaturated carbonyls. Electron-rich alkenes are also effective, but give opposite regiochemistry.
Simple alkenes often give mixtures of products.
• Ligands: Phosphines are most common (PPh3, Pt-Bu3, etc.). There are a lot of examples of
ligand-free catalyst systems that likely proceed through palladium nanoparticles.
• Reaction conditions: Typical bases include amines and inorganic bases (carbonate, phosphate).
Solvents are often polar aprotic. Reaction generally requires high temperatures (80-150 °C).
The neutral mechanism is favored in less polar solvents and when the leaving group is a halide. The
ionic mechanism is more likely in highly polar solvents, when a halide abstracting reagent (Ag(I) salts) are
used, and in dipolar aprotic solvents (DMF).
Ligand Substitution: The key step is coordination of the alkene to the Pd complex via an associative
(usually) ligand substitution mechanism. Either a neutral ligand (usually phosphine) or an anionic ligand
may be the leaving group, resulting in two pathways (next page): neutral or non-polar and ionic or polar.
The polar mechanism becomes more important when X is a good leaving group (I- or –OTf), when
chelating phosphines are used, or in polar solvents (DMF, water, ionic liquids).
Migratory Insertion: The majority of the evidence shows that the migratory insertion is largely concerted.
With more electrophilic Pd centers and electron rich alkenes, a cationic mechanism is also possible, in
which the Pd adds to the alkene electrophilically before delivering the aryl nucleophile.
Kevin Shaughnessy
138
H H
H
Ar R L
R
Ar
L Pd Ar
H L Pd
L Pd Migratory
L Insertion R
L
- X- + X-
ß-H elimination
H H
R
R + Ar
X- X-
Ar X Pd L
L Pd H
L
L R R
Ionic or
Polar Mechanism
X-
L4Pd
Ar
R -2L ArX
B: HB+ Cl-
L L
X Pd H L Pd L L Pd Ar
Reductive Oxidative
R L Elimination Addition X
Neutral or
Ar Non-Polar Mechanism
L H H
R R
Ar L
Ar
X Pd H X Pd L X Pd Ar
L L L
R R
-L +L
ß-H elimination
H H L L
H R R
Ar Ar
R
X Pd X Pd Ar
H Migratory
X Pd L Insertion L
L
Kevin Shaughnessy
139
Regio- and Stereoselectivity: Migratory insertion can place the aryl group on either carbon of the alkene.
The placement can be controlled electronically. With electron deficient alkenes and styrene derivatives,
the aryl group is generally placed b to the Ph or EWG, thus placing the aryl group on the most
electrophilic carbon. For vinyl ethers, the opposite regiochemistry is seen to again place the aryl group
on the electrophilic carbon. With simple alkenes, a mixture of products is usually obtained that will be
governed by steric factors of the alkene and catalyst species. b-Hydride elimination must occur through a
syn-coplanar conformation. When possible, the elimination will occur to give the more stable trans-
alkene.
Pd
Ligand
Br Base
+ E E
E = Ph, EWG (CN, C(=O)R, NO2)
Pd
Ligand R
Base +
Br + R R
Pd
Ligand
Br Base OR
+ OR
H Ph
H Ph Ph H Ph H
H H H H
L Pd L Pd L Pd L Pd
Ph Ph
X X H X H X
H Ph H Ph
Z E
Trost-Tsuji couplings:
As discussed in section 7, nucleophilic attack on h3-allyl species results in formation of a new C-C
or C-heteroatom bond.
Ph Ph NaCH(CO2Et)2
Ph Ph
+ P(PPh3)4 + NaCl
Pd PPh3
Cl PPh3
EtO2C CO2Et
The process involves oxidative addition into an allyl-leaving group species followed by
nucleophilic attack on the resulting palladium allyl. This process gives the product and
regenerates palladium(0).
Kevin Shaughnessy
140
+
(dppe)Pd(0) Ph (dppe)Pd(0)
Ph Ph
Pd OAc
OAc Ph2P PPh2
58 % ee
47 % ee
CO2Et
CO2Et
Ph
EtO2C CO2Et
37 % ee
Because a Pd(0) reagent is regenerated, the reaction can be catalytic.
LnPd
X
L2Pd
Nu
Nu +
Pd X-
Pd L L
L L
Nu-
Typical nucleophiles for these reactions are amines and stabilized carbanions. The leaving group
on the allylic group can be a halide, ester, or in some cases phosphonate. Esters, particularly
acetate, are most widely used since allylic alcohols are readily prepared. The methodology has
been applied to a wide range of synthetic problems.
Kevin Shaughnessy
141
H
OAc N
(Ph 3P) 4Pd N
N N
H
J. Am. Chem. Soc., 1976, 98, 8516
O
CO2H
O (PPh 3)4Pd
CO2Et
EtO 2C CO2Et CO2Et
Chem. Rev., 1989, 89, 1513
The most significant advance in this reaction has been the development of efficient asymmetric
versions of this catalytic cycle (Chem. Rev., 1996, 96, 395). This work was originated by Trost,
but today numerous researchers are working to develop ligands to allow for general, highly
selective allylic substitution reactions.
(COD)PdCl2 O O
O O O
L L= NH HN
O O O
NHTs TsHN 98 % Yield N
80 % ee Ts PPh2 Ph2P
In this case the mode of enantioselection probably involves coordination to the alkene and then
selective attack on one of the meso leaving groups. The ligand only allows attack at one of the
leaving groups, resulting in selective formation of a single Pd-allyl species. Rapid intramolecular
trapping of the allyl prevents racemization.
Ph2 Ph2 Ph2 Ph2

P P P P
Pd Pd
- Lg-
Lg Lg Lg
Kevin Shaughnessy
142
Molecular model of a Pd complex of Trost's ligand.
Cu-Catalyzed Coupling
Ullman (Ber. Dtsch. Chem. Ges. 1903, 36, 2382) and Goldberg (Ber. Dtsch. Chem. Ges. 1906, 39, 1691)
reported the coupling of aryl halides with anilines and amides, respectively. These reactions used
stoichiometric amounts of copper metal and/or copper salts and generally required high temperatures
Kevin Shaughnessy
143
(150-200 °C). This reaction represented the state of the art for arylation of N, O, and S until the
development of Pd-catalyzed reactions by Buchwald and Hartwig.
Ullmann
Cu
I + HN N
K2CO3
2 3
PhNO2, reflux
Goldberg
O
O
Br CuI
+ N
N
H K2CO3, reflux
In recent years, copper-catalyzed couplings have seen a resurgence with the development of ligand-
promoted versions of the Ullmann and Goldberg reactions.Diamines, amino acids, and diketonate ligands
are the most commonly used ligands, although a wide range of N and O chelating ligands can be used
successfully (Review: Chem. Sci, 2010, 1, 13; Angew. Chem. Int. Ed., 2009, 48, 6954; Acc. Chem. Res,
2008, 41, 1450). Cu-catalyzed reactions tend to work better than Pd-catalyzed versions for arylation of
amides and azoles. In addition, copper is significantly cheaper than Pd.
Cu (5 mol%)
Br DMEDA (20 mol%) N
N K3PO4
H toluene, 110 °C, 24 h 99%
The mechanism for the Cu-catalyzed couplings is not as well understood as for Pd-catalyzed reactions
(Dalton Trans. 2010, 39, 10338). Both radical and concerted mechanisms have been proposed for the
aryl halide activation step. The most commonly accepted mechanism involves coordination of the
nucleophile to the copper center followed by oxidative addition of the aryl halide to give a Cu(III)
intermediate and reductive elimination to form the bond. The Cu(III) intermediate has not been observed.
LnCuX
NuH, B–
Ar X
HB, X–
X
LnCu Ar LnCuNu
Nu
ArX
Note that the order of steps is reversed from that in Pd-catalyzed coupling. Evidence for the nucleophile
coordinate occurring first is based on the fact that LnCuX species do not react with aryl halides, while
LnCu-Nu complexes do (see reaction below). Computational studies show that LnCu-Nu undergoes
oxidative addition with lower barrier than LNCuX (Organometallics, 2007, 26, 4546).
Kevin Shaughnessy
144
Me H O H O
MeO I Me
N N
Cu N Cu I MeO N
N N
Me H Me H
Buchwald, J. Amer. Chem. Soc, 2009, 131, 78
One important role of the ligand appears to be to prevent formation of [Cu(NR2)n](n-1)– complexes, which
are catalytically inactive. (JACS, 2005, 127, 4120).
N N
N ArX
R2N Cu NR2 Cu NR2 Product
N
ArX
No Reaction
The mechanism of the Ar-X activation step is still a matter of debate. Both 2 e oxidative
addition/reductive elimination and radical pathways have been proposed.
Oxidative Addition/Reductive Elimination

N ArX N X N
Cu NR 2 Cu Ar Cu X + Ar-NR2
N N NR 2 N
Single Electron Transfer (SET)

+
N ArX N N X
CuI NR 2 [Ar-X]•— + Ar•
CuII NR 2 CuII
N N N NR 2
N
Cu X + Ar-NR2
N
Hartwig used a number of experiments to conclude that the step is likely an oxidative addition/reductive
elimination sequence (JACS, 2008, 130, 9971). How do these results support a non-radical pathway?
1. Comparison of reactivity of aryl halides having similar reduction potentials and halide dissociation
rates.
Kevin Shaughnessy
145
•–
Cl e Cl k = 1.6 X 108 – 4.5 X 108
+ Cl–
-2.03 V NC
NC NC
•–
Br Br
e k = 6.3 X 107 – 1 X 1010
+ Br–
-2.17 V
O
Me H O Me H
N Cl N N
Cu N + + Cu Cl
N toluene N
NC 110 °C NC
Me H Me H
2h 0%
O
Me H O Me H
N Br N N
Cu N + + Cu Br
N toluene N
Me H 110 °C Me H
97%
2h
2. Use of a radical clock
O I
O N
N O
Cu N + O + O
N DMSO
110 °C
2h
95.5% 1.9%
O not observed
R = H, pyrrolyl
A computational study by Buchwald and Houk suggested that a SET or atom transfer pathway had the
lowest energy barrier, depending on the ligand and nucleophile, however. JACS, 2010, 132, 6205. The
computation study could be consistent with Hartwig's experimental results if the free radical intermediate
has a very short lifetime.
Kevin Shaughnessy
146
Oxidative
Addition/ X
L nCuIII
Reductive
R1R 2N
Elimination
+
L nCuII NR1R 2
SET •–
X
X
NR1R 2
L nCuI NR1R 2
Atom +
L nCuII NR1R 2
Transfer X Ln CuI NR1R 2
s-Bond
L nCuI NR1R 2
Metathesis
X
Comparison of Pd- and Cu-catalyzed coupling
Parameter Pd Cu
Metal cost ca. $3,000/mol ca. $0.6/mol
Loading ≤ 1 mol % 5-10 mol %
Ligands Phosphines, NHC Amines

ArX Scope ArI, ArBr, ArCl, ArOSO3R ArI, ArBr (ArCl rare)
N Scope Amines Best with amides, azoles.
Amides, azoles known but limited Amines also work
Temperature rt-100 °C 80-150 °C
The Pd- and Cu-catalyzed carbon-heteroatom bond-forming reactions are often complementary to each
other. The example below was reported by Buchwald (JACS, 2003, 125, 6653). Using copper, the indole
nitrogen is exclusively arylated. In contrast, Pd primarily gives arylation at the amino nitrogen. Copper-
catalyzed reactions tend to favor more acidic and softer nitrogen nucleophiles. Palladium generally gives
better results with more nucleophilic amine nitrogens.
Kevin Shaughnessy
147
CuI (5 mol %), H 2N

DMEDA (10 mol %) A
N
K2CO3, dioxane,
110°, 24 h (98%)
H 2N >20:1 A:B
N
H n-Bu Cl
H
Pd2(dba)3 (1 mol %), N
X-Phos (5 mol %)
N B
K2CO3, t-BuOH n-Bu
H
110°, 3 h (80%)
1:8 A:B
Kevin Shaughnessy
148
10-Hydrocarbon Functionalization by C-H Activation
Organic chemistry has historically been based on the conversion of functional groups into desired
functional groups. For example, cross-coupling reactions require a preexisting halide. Often these
functional groups had to be introduced from the original hydrocarbon starting material. Directly
functionalizing C-H bounds would allow chemists to avoid this prefunctionalization. In contrast, there are
relatively few approaches to directly converting alkanes or arenes into functionalized derivatives. Alkanes
can be radically halogenated and arene C-H bonds can undergo electrophilic aromatic substitution, for
example. We have discussed that metals can insert into C-H bonds. If these intermediates can be
functionalized, a catalytic process is possible. Challenges with this approach are first activating the
strong and relatively unreactive C-H bond. If this can be achieved, the question is how to do this
selectively.
Non-Directed C-H Activation—A long standing goal has been identifying methods to selectively oxidize
alkane or arene C-H bonds in a selective manner. Alkanes are particularly challenging substrates as they
are poor ligands. Review, ACS Central Sci., 2016, 2, 281.
Selective Oxidation of Alkanes: Shilov-type oxidation of methane
[PtCl4]2-
CH4 + [PtCl6]2- + H2O CH3OH + [PtCl4]2- + 2HCl
Zh. Fiz. Khim., 1969, 43, 2174
CH3OH + HCl
[PtCl4]2- CH4
H2O
HCl
2- 2-
Cl Cl
Cl
Cl Cl Pt
Pt Cl CH3
Cl CH3
Cl
[PtCl4]2- [PtCl6]2-
While impractical (stoichiometric in Pt), the Shilov system represented a very selective method for
alkane oxidation.
Reactivity of H-CH3 100 X higher than that of H-CH2OH
Very strong preference for oxidation of C-H bonds on sterically unhindered methyl groups.
Pt(II)
oxidant
OH HO OH
Kevin Shaughnessy
149
For original Shilov chemistry, the Pt(0)/Pt(II) and Pt(II)/Pt(IV) redox couples have similar potentials.
Thus Pt(II) can also disproportionate into Pt(0) and Pt(IV). This leads to precipitation of Pt metal and
undesired side reactions.
Catalytica System (Roy Periana, now at USC): Science, 1998, 280, 560
N N
N N
Pt
Cl Cl
CH4 + 2 H2SO4 CH3OSO3H + H2O + SO2
70 % one-pass yield
N H2SO4
N X HN N X
Pt Pt X = Cl, OSO3H
N N X N N X
CH4
N X
CH3OR Pt X-
N HN N
HX N
=
CH4 N
ROH N N
HX
R = H, SO3H X
N OSO3H N X
Pt Pt
N CH3 N CH3
OSO3H
SO2 + 2 H2O 3 H2SO4
In principle an industrially viable series of processes can be envisioned:
CH4 + 2 H2SO4 CH3OSO3H + H2O + SO2
H2O + SO2 + 0.5 O2 H2SO4
CH3OSO3H + H2O CH3OH + H2SO4
Net: CH4 + 0.5 O2 CH3OH
Kevin Shaughnessy
150
Problems limiting commercial application:

9. Turnover frequencies are 2 orders of magnitude too low
10. MeOH recovery from concentrated sulfuric acid is too costly
11. SO2 reoxidation to sulfuric acid is impractical
Most alkane C-H activation occurs at the least hindered C-H bond (1°>>2°>>3°). Catalysts selective for
secondary or tertiary C-H bonds would be desirable. Christina White (Illinois) has developed such a
system (Science, 2007, 318, 783; Science, 2010, 327, 566).
Fe cat
OAc AcOH OAc N
O O N NCCH3
H 2O 2 OH Fe = Fe
F 3C N F3C N N NCCH3
MeCN, rt N
H H
Alkane Dehydrogenation:
Alkene hydrogenation is well precedented. Would it be possible to identify systems where the
reverse reaction (alkane dehydrogenation) would be favored?
R H H
H H
LnM H LnMn-2 + H
LnM LnM H R
H
R
R
H2
The first catalytic system:
In order to drive the reaction towards dehydrogenation, it is usually necessary to remove H2 from the
reaction system. Often a reactive alkene is used as a hydrogen acceptor. 3,3-Dimethyl-1-butene is
used as a hydrogen acceptor because of its high heat of hydrogenation.
ReH7(PR3)2
+
t-Bu
t-Bu
J. Chem. Soc., Chem. Comm. 1982, 1235
Kevin Shaughnessy
151
PAr3
H O
Ir CF3
H O
H H PAr3
heat
R R +
t-Bu
R R
t-Bu
J. Amer. Chem. Soc. 1987, 109, 8025
PAr3
H O
R Ir CF3
H O t-Bu
PAr3
PAr3
PAr3
H O2CCF3
H O2CCF3 Ir
Ir hν H t-Bu
H R - H2 PAr3
PAr3
Ar3P O
Ir CF3
Ar3P O
PAr3
PAr3 H O2CCF3
Ir
H O2CCF3
H Ir t-Bu PAr3
PAr3
PAr3
O2CCF3
R Ir
PAr3 t-Bu
R
t-BuCH=CH2 converts the Ir dihydride to a coordinatively unsaturated Ir(I) complex. The driving force
for this reaction is the very exothermic hydrogenation of t-BuCH=CH2. The unsaturated Ir(I) species
can then oxidatively add the substrate.
The need for t-BuCH=CH2 can be eliminated by using light to remove H2 from the Ir(III) dihydride.
Thus the driving force is provided by the incoming photon.
The dehydration can also be carried out thermally without an H2 acceptor if hydrogen can be purged
from the reaction system. Catalyst stability becomes an important issue under these conditions (150
- 230 ˚C). In particular, ligand metallation and other decomposition pathways become important.
Kevin Shaughnessy
152
PR2
H
Ir
H
PR2
R = t-Bu, i-Pr
+ H2
230 ˚C
TOF = 12 /minute
TON = 1000 mol/mol cat
Angew. Chem. Int. Ed. 2001, 40, 3596-3600
Borylation of Alkanes:
1. Stoichiometric Functionalization (Science, 1997, 277, 211)
Bcat'
85 %
Cp*
O hν
[Cp*W(CO)3]- + ClB OC Bcat' 74 %
W
O OC CO Bcat'
ClBcat'
Bcat' 55 %
cat'B
2%
Possible Mechanisms:
Cp* RH Cp*
hν OC H
OC Bcat' W + RBcat'
W
Path A OC CO
OC CO
-CO Path B
hν reversible? RH
Cp*
OC Bcat'
W
OC
Observations:
• The reaction is not inhibited by CO
• Photolysis under 13CO does not result in incorporation of 13CO into the complex
• Reaction in pentane and pentane-d12 showed indistinguishable conversion rates, but a large
isotope effect was observed in a 1:1 mixture of C5H12 and C5D12
Kevin Shaughnessy
153
• Photolysis of the W-Bcat' complex in the presence of PMe3 in pentane led to formation of the
PMe3 adduct in addition to pentyl-Bcat'. The ratio of PMe3 complex:pentylBcat' was
dependent [PMe3]
Formation of a strong B-C bond drives this reaction (B-C is 10-15 kcal/mol stronger than C-H,
while M-B and M-H have similar bond strengths).
2. Thermal, metal catalyzed alkane and arene borylation (Science, 2000, 287, 1995, J. Am. Chem.
Soc., 2002, 124, 390-391, Science, 2002, 295, 305)
To carry out the reaction thermally, need a complex where the ligands can be extruded upon
heating (H2 or alkenes).
Cp*
M
+ B2pin2 Bpin + HBpin

150 - 200 ˚C
M = Ir: 58 %, slow
M = Rh: octylBpin > B2pin2 consumed
Overall yield 84 % based on boron
A variety of ethylene derived borane products were observed. Therefore, a catalyst that would
release an unreactive fragment was required.
Rh
Proposed Mechanism: JACS, 2005, 127, 2538
Kevin Shaughnessy
154
Cp* Y-Bpin
RBpin
Rh
H X
RH Cp*
XBpin Cp*
Rh -C6Me6 pinB X Y Bpin
Rh Rh
R H H X
X, Y = H, Bpin
stereochem
unknown
Cp*
Rh HY
pinB X
R-H
C-C Bond Formation
In addition to C-heteroatom bond formation, a large number of C-C bond-forming reactions have been
reported. Often these involve the coupling of an aryl halide with an arene. The C-X bond is activated by
a normal oxidative addition process. The C-H bond is activated by a heterolytic C-H bond activation (see
below).
MeO Pd(OAc)2
Br
PCy3 MeO
O K2CO3, DMA
130 °C O 92%
Fagnou, JACS, 2006, 128, 581
Pd(OAc)2 (3 mol %)
Br DavePhos (3 mol %)
Pivalic acid 81%

cosolvent K2CO3
DMA, 120 °C
Fagnou, JACS, 2006, 128, 16496
Several mechanisms have been proposed for these types of transformations. Electrophilic aromatic
substitution-type reactions were commonly invoked. Echevarren proposed a heterolyic mechanism. For
Pd(II), OA/RE was expected to be less likely. (J. Am. Chem. Soc. 2007, 129, 6880-6886).
Kevin Shaughnessy
155
B
SEAr H
X
M
L -HB+ X–
H
σ-bond X
metathesis
M
X L
-HX
M
H M
L L
B
H
intermol. X
activation M
L
-HB+ X–
X H
OA/RE M
L
-HX
In an effort to distinguish between these mechanisms, Echevarren performed two competition

experiments. In the first, the substrate had two electronically different ring systems. In the second, a KIE
was measured.
N
N N
1) Pd(OAc)2, L
K2CO3, DMF
CH3
CH3 H3C
Br
L= PPh2
93%
Me2N 2.1:1
D D D
D D D D D D
1) Pd(OAc)2, L
K2CO3, DMF
D D D
2) DDQ D
D
Br
kH/kD = 6.7
For C-H bond activation by palladium catalysts in the presence of carboxylate anions, a σ-bond
metathesis mechanism using the carboxylate as an intenral base has been implicated for both sp3
Kevin Shaughnessy
156
(Rousseaux, and Fagnou, J. Am. Chem. Soc. 2010, 132, 10692-10705.and sp2 (Fagnou. J. Am. Chem.
Soc. 2008, 130, 10848-10849) C-H activation. This type of mechanism is often called concerted
metalation/deprotonation (CMD) and is typical for lower-valent late transitions metals, particularly d8
square planar complexes (Pd(II), Rh(I))
sp2
R3P Pd
H R3P Pd H R3P Pd
O O
O O HO O
R
R R
sp3
O Me
NMe2 + RCO2– N H
NMe2 Pd(PCy3)2 -PCy3
O O
O
Br Pd PCy3 Pd R
Cy3P Br Cy3P O
O
O
Me
Me N
N
H
Pd Pd O
Cy3P O H Cy3P
O O
R
R
It is even possible to have both reaction partners involve C-H activation. Fagnou reported the cross
coupling of electron rich azoles with arenes. This type of reaction requires an oxidant to convert the
Pd(0) species formed upon reductive elimination back to Pd(II). Good yields of cross-coupled products
were obtained, although a large excess of the arene had to be used. Science, 2007, 316, 1172-1175
Ph
MeO Pd(TFA)2 (10 mol%) MeO
+
N Cu(OAc)2 N
Ac 3-nitropyridine Ac
CsOPiv (40 mol%) 84%
PivOH
Kevin Shaughnessy
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Directed C-H functionalization: A way to overcome the selectivity issue is to use a coordinating group
in the substrate to direct the metal to a particular C-H bond. Examples where the C-H activation is
promoted by coordination to a Lewis-basic functional group are very common. (Chem Rev, 2010, 110,
1147) The coordinating group directs C-H activation to a nearby C-H bond. The resulting metal-carbon
can then be functionalized.
L Mn L Mn base L Nu L
Mn Mn+2
C H C H C oxidant C Nu
L L
C Nu C H
The first examples of this type of reaction reported by Murai in the early 1990s. He showed that a Ru
catalyst would promote an ortho alkylation of aryl ketones. The ketone served as a directing group to
promote C-H activation in the ortho position.
O O
RuH2(CO)(PPh3)3
Si(OEt)3
toluene, reflux
Si(OEt)3
Nature, 1993, 366, 529
The mechanism has been shown to involve the directed oxidative addition of an ortho C-H bond by Ru.
Alkene insertion into the Ru-H gives a alkyl group that undergoes reductive elimination. Since there is a
closed redox loop, no oxidant is needed.
Kevin Shaughnessy
158
R RuH2(CO)(PPh3)3
L + R O
O
R CO + R
L
PPh3 PPh3 PPh3
O Ru PPh3 L Ru PPh3 Ph3P Ru O
PPh3 Ph3P
PPh3 L
L = PPh3, CO
R
Ph3P Ph3P PPh3
PPh3 PPh3 PPh3 Ph3P Ru O
Ph3P Ru O Ph3P Ru O Ph3P Ru O
H H Ph3P
H
R
PPh3
PPh3 R
This type of reaction received little attention for almost a decade. People then began exploring palladium-
catalyzed arylation of C-H bonds using directing groups. For these types of reactions, an oxidant is often
needed. In the example below from Sanford, the Ph2I+ species is able to oxidatively add to the Pd(II)
palladacycle. The bond is formed by reductive elimination.
N Pd(OAc)2 (5 mol%) N
H 3C H 3C
+ [Ph2I]BF4
Ph
AcOH
Sanford, M. S.; et al. J. Amer. Chem. Soc. 2005, 127, 7330-7331.
Kevin Shaughnessy
159
N N
H3C H 3C
Ph PdII
N N
H3C PdII H 3C PdII
Ph
AcO–
AcOH
N N
H3C H3C
PdIV PdII
PhI Ph2I+
C-heteroatom bond formation:
C-H activation is an effective method to introduce heteroatoms, such as halogens, O, or N into aromatic
systems.
Kevin Shaughnessy
160
O Pd(OAc)2 (cat) O
PhI(OAc)2
N N
MeCN, 100 °C
AcO
HO HO
N N X
Pd(OAc)2 (cat)
NXS
AcOH, 120 °C
Pd(OAc)2
NHTf NHTf
N F
NMP, DCE
120 °C F
The mechanism is believed to proceed through a Pd(IV) intermediate. Pd(IV) undergoes reductive
elimination of C-X bonds much easier than Pd(II). The intermediacy of Pd(IV) has been shown in
stoichiometric studies.
F
F
Pd
XeF2 N 150 °C N
N NNs
Pd + Pd(II)
N N MeCN, rt F
Ns
Ritter, JACS, 2008, 130, 10060

Sanford, JACS, 2009, 131, 3796
Alkane Functionalization
In addition to arene C-H activation, ligand directed activation of sp3 bonds is common.
OAc
Pd(OAc)2 (cat)
N t-Bu lauroyl peroxide N t-Bu
t-Bu t-Bu
O Ac2O, 50 °C O
OAc
Pd(acac)
N ligand N
Ac2O, AcOH, O2
80 °C
Kevin Shaughnessy
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Remote Functionalization
Disadvantages of using a directing group are: 1) the directing group must be introduced using a
preexisting functional group. This group, or its derivatives, must be tolerated in the final product. 2) The
directing group can typically only direct the metal to a nearby bond, such as the ortho position of a
substituted arene.
Jin-Quan Yu and his group have demonstrated that more remote functionalization is possible using
cleverly designed templates that direct the metal to a desired bond.
NHT
iPr iPr
O
Pd(OAc)2 O
N O Ag(OAc)
H
F OEt HFIPA
CO2Et
H N iPr iPr
O
Org. Lett, 2018, 20, 425
N
H
F
N
H Pd
Pd(OAc)2 (10 mol %)

N Ac-Gly-OH (20 mol %)
O CO2Et
N S AgOAc, HFIP, 55 °C EtO2C N
C O
T
MeO N
H O
S O
JACS, 2014, 136, 10807 Pd
N
C
MeO
Recently, Yu has reported an example where the directing group is not covalently bonded to the
substrate. Rather a metal-coordination interaction is used to bind the substrate to the directing ligand.
Nature, 2017, 543, 538
Kevin Shaughnessy
162
O2S NH HN SO2
CO2Et
N 20 mol % N
Pd(OAc)2 (30 mol %)

N Ac-gly-OH (20 mol %) N
CO2Et
AgBF4, Cu(OAc)2
HFIP, 110 °C, air
O2S N N SO2
N Pd N Pd
H H
N N
Kevin Shaughnessy
163
11-Hydrogenation of Unsaturated Compounds
Alkene hydrogenation is one of the oldest metal catalyzed reactions (Pd/C) and one of the first
homogeneous catalytic cycles to be carefully studied mechanistically. There are three steps involved in
nearly all hydrogenation reactions.
- Hydrogen activation: oxidative addition, heterolytic, or homolytic

- Migratory insertion
- Elimination of alkane: Reductive elimination, s-bond metathesis or homolytically
Wilkinson's Catalyst: RhCl(PPh3)3
H2
RhCl(PPh3)3 (cat)
H H
C6H6, EtOH
The rates of hydrogenation of alkenes by Wilkinson's catalyst mirror their relative binding affinity to the
metal center. Differences in rate between the alkenes is about 50X. Alkenes that bind very tightly (i.e.,
ethylene) give slow hydrogenation rates, though.
R R R R R
> > > > >>
R R R R R R R R
Proposed mechanism as elucidated by Halpern: (J. Mol. Cat., 1976, 2, 65; J. Am. Chem. Soc., 1977, 99,
8055; J. Am. Chem. Soc., 1980, 102, 838; Science, 1982, 217, 401)
H2 H
L k2 L H
L L L
Rh Rh
Rh Cl L
Cl L Cl L -H2
1
7 k-2 3 L
+L -L K5
+L -L
k-1 k1
H2 H H
L S k4 L H k7 L H
Rh Rh Rh
L Cl L Cl L -H2 Cl L Cl L
Rh Rh k-7
2
L Cl L k-4 4 S
8 5
H2
k8
k6
L H H H
L Cl H L
Rh Rh Rh
L Cl H Cl L H
S 6
9 L
Kevin Shaughnessy
164
The Rh complexes outside of the box have been observed under the catalytic conditions. None of the
compounds inside the box have been observed, but based on the evidence are believed to be the actual
species involved in the catalytic cycle.
The hydrogenation reaction occurs in two steps:
• Dihydrogen activation
• Alkene hydrogenation
Since H2 is activated first, this is often called the hydride path.
Dihydrogen activation:
Halpern's evidence supports an initial dissociation of PPh3 prior to oxidative addition of H2. The rate of
oxidative addition is inhibited by increased [PPh3]. In fact the direct addition of H2 to 1 to give 3 in the
presence of excess PPh3 occurs very slowly. (J. Mol. Cat., 1976, 2, 65; Inorg. Chim. Act. 1981, 50, 11).
Oxidative addition of H2 to 2 was estimated by Halpern to occur 104 X faster than to 1, which was later
confirmed by generating 2 by flash photolysis. (J. Am. Chem. Soc., 1985, 107, 1794 and 1986, 108,
4838).
H
L L L H
Rh H2 Rh
Cl L excess L Cl L
1 L 3
-L hν
H H
L S L H L L H
Rh H2 Rh Rh
Cl L Cl L Cl L
2 S L 3
4
Wilkinson originally proposed a similar mechanism based on his assumption that k1/k-1 would be large. In
fact the equilibrium constant is approximately 10-5. Wilkinson's error was due to the oxygen sensitivity of
RhCl(PPh3)3, which reacts with oxygen to give Ph3PO as a weakly bonded ligand.
2 has a strong tendency to dimerize to 8, although this is not a significant process under higher H2
pressures. The alkene complex 7 also does not represent a significant trap for the Rh species, except in
the case of tightly binding alkenes such as ethylene.
Olefin Hydrogenation:
Kinetic studies were carried out on the reaction of 3 with a large excess of alkene.
H
L H H2 L L
Rh Rh +
Cl L Cl L
L
Treating the conversion of 3 to 5 as a rapid pre-equilibrium (K5) and the conversion of 5 to 6 as the rate
determining step results in the following rate expression.
Kevin Shaughnessy
165
−d [3] # K 5k6 [alkene] &

=% ([3] = kobs [3]
dt $ [L]− K 5 [alkene]'
K 5k6 [alkene]
kobs =
[L]− K 5 [alkene]
This rate expression predicts that a plot of 1/kobs versus [L]/[alkene] should be linear with slope = 1/K5k6
and an intercept of -1/k6.
€
1 " 1 %" [L] % 1
=$ '$ '−
kobs # K 5k 6 &# [alkene]& k 6
Plotting data from experiments where [L]/[alkene] was varied over a wide range were linear and gave
values for K5 (3.4 X 10-4) and k6 (0.2 s-1). Kinetic results suggest that k8 (reductive elimination) is
€
sufficiently fast that the reverse of hydride migration (ß-hydride elimination) is not observed. These
results account for the lack of isotopic exchange when the reaction is carried out with D2.
The fact that 6 is not trapped by phosphine can be inferred from the lack of [PPh3] dependence on the
migratory insertion step.
Although this mechanism has been carefully worked out, variation of the ligand or the substrate can
drastically alter the observed mechanism and rate expressions.
– Alkenes that bind more strongly than cyclohexene (i.e., styrene) indicate a parallel mechanistic path
where two equivalents of styrene bind to the metal center.
– Ethylene which binds very strongly to the metal center appear to follow path where the alkene binds
prior to H2 oxidative addition.
– Use of more electron rich trialkylphosphines can strongly affect the dissociative equilibria altering the
mechanism.
Cationic Rhodium catalysts [RhL2S2]+
Ph2 Ph2
P 2 H2 P S
Rh Rh +
P P S
Ph2 Ph2
These systems work particularly well for alkenes with other functionality that can coordinate to the
electrophilic rhodium center.
Ph2
P S
Rh
P S
Ph2
H CO2Me
H CO2Me H2 H H
Ph NHAc
Ph NHAc
racemic
Kevin Shaughnessy
166
For these cationic metal complexes, the mechanism proceeds by initial alkene coordination followed by
H2 oxidative addition, hydride migration, and reductive elimination. Halpern has also studied the
mechanism of this catalytic cycle in detail. (J. Am. chem. Soc. 1977, 99, 8055, and 1980, 102, 838;
Science, 1982, 217, 401)
H CO2Me
(MAC) H
Ph NHAc E N
Ph2 Ph2
P S k1 P CH3
Rh Rh Ph
P S k-1 P
Ph2 Ph2 O
10 11
H CO2Me
H H H2
Ph NHAc S k2
k4
CH3
Ph
S OE
Ph2 E NH
Ph2
P NH k3
Rh P
P O Rh Ph
Ph2 H CH3 P H
S Ph2 H
13 12
Complexes 10, 11, and 13 can be observed in the catalytic cycle. In this case the observed species are
part of the actual catalytic cycle.
Complex 10 is in equilibrium with the alkene complex 11. Even relatively weak π-ligands like benzene
coordinate strongly to the electrophilic Rh center. Since benzene is not reduced by this catalyst, it acts as
a competitive inhibitor. For alkenes such as MAC, the equilibrium is rapidly established and lies far
towards the alkene complex. Complex 11 has been characterized by X-ray crystallography.
At 25 ˚C, oxidative addition of H2 to 11 is the rate limiting step, but at -40 ˚C reductive elimination
becomes rate limiting. Hydride migration to the alkene occurs very rapidly in contrast to Wilkinson's
catalyst.
These systems are of particular interest because they allowed the first enantioselective hydrogenations of
prochiral alkenes.
Asymmetric Hydrogenation:
Coordination of a prochiral alkene to a transition metal center produces a pair of enantiomeric alkene
complexes that are converted to enantiomeric hydrogenation products. If the starting organometallic
complex is chiral, though, the alkene complexes are diastereomers of each other.
R R R MLn
LnM
R' R' MLn R'

Prochiral
alkene
Kevin Shaughnessy
167
The first commercial application of this idea was the synthesis of L-Dopa commercialized by Monsanto.
This seminal work by William Knowles was recognized with the Nobel prize in 2001.
H CO2Me
[(DIPAMP)Rh(MeOH)2]+ CO2-
H2 CO2Me
NHAc H3O+ H NH3
MeOH H NHAc HO
HO
OH
HO OH OMe OH
L-DOPA
100 % yield
95 % ee
P P
MeO
DIPAMP
DIPAMP is chiral at phosphorous. Other ligands, which have chiral backbones have become more
popular because of their ease of synthesis from optically pure organic precursors.
P
O O PPh2
PPh2 P
PPh2 PPh2 Ph2P PPh2
DIOP CHIRAPHOS BINAP DUPHOS
P M P
Early studies by multinuclear NMR showed only a single diastereomer was produced upon coordination
of MAC to Rh((S,S,)-CHIRAPHOS)+ (14' or 14"). It was originally assumed that the major isomer
observed by NMR would be the one that led to the observed product enantiomer. When the alkene
adduct was characterized crystallographically, the structure was determined to be 14" (re face). This
would predict formation of the S-product, but in fact the (S,S,)-CHIRAPHOS ligand gives predominately
the R-isomer.
With the ligand (R,R)-DIPAMP, both 14' and 14" are observed in unequal amounts, although their
absolute configuration was not determined. At low temperatures, where the diastereomers do not
interconvert, the minor diastereomer reacts with H2 much more rapidly. The results suggested that the
minor diastereomer of 14 reacts with H2 ca. 1000 times faster than the major diastereomer. (J. Chem
Soc., Chem. Comm. 1980, 344; 1983, 664; and 1985, 575)
Kevin Shaughnessy
168
P S
Rh
P S
H CO2Me
k'1 k"1
Ph NHAc
k'-1 k"-1
H H
E N N E
P CH3 H3C P
Rh Ph Ph Rh
P P
O O
14' 14"
H2 H2
k"2
k'2
E H H E
P N N P
H CH3 H3C H
Rh Ph Ph Rh
P P
H O O H
15' 15"
S S
k'3 k"3
Ph Ph
P P
CO2Me MeO2C
H H
Rh Rh
P S S P
O NH HN O
H3C CH3
16' 16"
H H
H3C N CO2Me MeO2C N CH3
O O
Ph Ph
(R) (S)
Kevin Shaughnessy
169
Mechanisms in which an initial rapid equilibrium is formed between reaction intermediates followed by
slow product forming steps are known as Curtin-Hammett-type mechanisms. This type of mechanism
turns out to be fairly common for these types of asymmetric hydrogenations. Two useful experiments that
can be used to probe for this type of mechanism are:
• Effect of changing H2 pressure

• Temperature effect on the enantioselectivity of the reaction
Hydrogenation of other unsaturated compounds
Burk developed the duPHOS family of ligands while working at DuPont. In addition to giving highly
enantioselective reduction of enamides, Rh complexes of duPHOS also give high ee's in the reduction of
hydrazones. (J. Am. Chem. Soc., 1991, 113, 8518; 1992, 114, 6266)
O
NHCOR" NHCOR"
O "R NHNH2
N [Rh(Et-duPHOS)]+ HN SmI2
NH2
R R' R R' H2 R * R' R * R'

72 - 97 % ee
O
O O
N HN Cl O
N PAr2
[Ir(cod)L2]+
L2 = Fe PPh2
H2
(S)-metachlor
Ciba-Geigy
Ryori Noyori was also a recipient of the 2001 Nobel Prize for his development and application of the
BINAP ligand. Using Ru(II) in place of Rh(I) resulted in a more general catalyst that could hydrogenate
ketones and imines as well as alkenes.
O O ((R)-BINAP)RuCl2 H OH O
OMe OMe
H2
99.5 % ee
This catalyst system has been commercialized for the synthesis of (R)-1,2-propanediol, which is used as
a precursor for the synthesis of the antibiotic levofloxacin.
Ionic Hydrogenation
The Noyori catalyst is believed to follow ionic mechanism in the reduction of carbonyls and imines. In an
ionic mechanism H2 is added as H+ and H-, rather than by a migratory insertion process. This mechanism
is particularly prevalent in the reduction of ketones and imines that can serve as proton acceptors. Chem.
Eur. J. 2004, 2366-2374.
Kevin Shaughnessy
170
Et
BAr4
OC Mo O Et
OC PCy3
O OH
+ H2
Et Et 4 atm Et Et
H
O
H
LnM Et Et
H2 H
LnM O H
Et LnM O
O LnM H
Et
Et Et
Et Et
OH
H
Et Et LnM O
H Et
Et H
A number of systems have been developed in which a Lewis basic site in the ligand environment serves
as the proton donor, while the metal provides the hydride. Shvo developed a system based on a Ru
complex of cyclopentadienone. Heterolytic oxidative addition of H2 gives a cyclopentadienol-ruthenium
hydride. Organometallics, 1997, 17, 133-138.
O H O
Ph Ph Ph
Ph Ph Tol OH
H2
H 2 Tol Ph
Ru Ru Tol Ru
Tol Tol OC
Tol H
OC CO OC CO OC
Ph
Tol OH Ph
Tol O OH
Tol Ph
O
OC Ru H Tol
Ru
Ph
R R'
OC H
R' R OC CO
H2
Kevin Shaughnessy
171
Noyori has developed a highly successful catalyst system based on ruthenium amine complexes. The
amine serves as the proton donor, while the ruthenium delivers hydride. These systems are highly
enantioselective catalysts for reduction of carbonyls and imines. Angew. Chem. Int. Ed. 2002, 41, 2008
and 2108.
Ph Ph Cl H2 Ph
P N
Ru
P N
Cl H2
Ph Ph Ph
OH
O
NHCH3
NHCH3
i-PrOH
CF3
O fluoxetine
antidepressant agent
NHCH3
This hydrogenation is an example of a transfer hydrogenation. Isopropanol serves as the source of

hydrogen. The isopropanol adds to the Ru center, followed by b-hydride elimination. The hydrogen
transfer step is believed to involved a 6-membered transition state in which the N-H and Ru-H both
deliver H at the same time. The transition state has been computationally modeled.
OH O
+ HCl O
HH HH R R' H
Cl H
P N P N Ru
Ru Ru
P Cl N P Cl N
O N
HH HH H
O
+ HCl
OH
OH
R * R'
HH HH
Cl HCl
P N P N
Ru Ru
P Cl N P Cl N
HH H
Kevin Shaughnessy
172
12-Carbonylation Reactions
CO is an important building block in industrial and academic synthesis. Incorporation of CO allows a

carbon to be added and usually results in the formation of a carbonyl product. CO is produced industrially
from the water-gas shift reaction in which CO2 and H2 can be reacted to form CO and water.
I. Carbonylation of alcohols and organic halides
The Acetic Acid process
Approximately 60 % of the 6.5 million metric tons (1,000 kg) of acetic acid made each year is produced by
the carbonylation of methanol.
[M(CO)2I2]- O
CH3OH + CO
OH
HI
1960: Original system developed by BASF
M = Co, 250 ˚C, 680 bar CO, 90 % acetic acid based on MeOH
1966: Monsanto Acetic Acid process
M = Rh, 150 - 200 ˚C, 20 - 60 bar CO, > 99 % acetic acid from MeOH, lower yield relative to CO
1996: BP Cativa™ process
M = Ir, improved catalyst stability, very high rates, and good product selectivity relative to both MeOH
and CO
Rhodium: The Monsanto Acetic Acid Process:
Adv. Organomet. Chem., 1979, 17, 255

Chemtech, 1971, 1, 600
U.S. Patent 3,769,329, 1973
[Rh(CO)2I2]-
O
HI
CH3OH + CO (30-40 atm)
180 ˚C OH
> 99 %
Virtually any source of Rh(I) and iodide catalysts can be used. These are converted under the
reaction conditions to [RhI2(CO)2]- and CH3I
The key steps in the catalytic cycle are: 1) anion assisted oxidative addition of MeI; 2) migratory
insertion of CO; 3) reductive elimination of acetyl iodide.
The use of I- is critical. Bromide gives rates that are 10X slower than iodide.
• Iodide is a good nucleophile
• Iodide is a weak Brønsted base
• Iodide is a good ligand for Rh
Kevin Shaughnessy
173
Rate = k[Rh]1[I-]1[CO]0[CH3OH]0
OH HI
CH3OH
H2O
O [RhI2(CO)2]- CH3I
I
CO O CH3
I
Rh CH3 I CO
I CO Rh
I CO
I
I
CO
The Me-Rh species can only be observed spectroscopically (J. Am. Chem. Soc., 1993, 115, 4093),
while the acyl rhodium species has not been observed.
Disadvantages of this system:

• Iodide is corrosive
• The rhodium catalyst is only stable under certain conditions (high CO pressure), so catalyst
recycling is difficult
• A heterogeneous version is unlikely
Iridium: The BP Cativa™ Process
Iridium catalysts have very high rates, but can have low selectivity.
The mechanism as determined by Forster (J. Chem. Soc., Dalton Trans., 1979, 1639; Adv. Catal.,
1986, 34, 81; J. Mol. Cat., 1982, 17, 299) showed that the iridium system is more complex
mechanistically than the rhodium system. There appear to be two catalytic cycles involving both
anionic and neutral iridium complexes.
Kevin Shaughnessy
174
HI H2
H2
HI, CO H I
I CO I CO
I Ir Ir
I CO I CO
I CO I
Ir I
I CO
Ir(CO)2I2H(H2O) CO
HI, CO2 CO, H2O
2 HI, CO2
CO, H2O HI
CO I- CO
HI
[Ir(CO)3I] [Ir(CO)2I2]-
CH3I
-CO
I- O CO
I
Ir(CO)2I CH3
I CO
CO CH3 I CH3 Ir
I I I CO
Ir O Ir O I
I CO I CO
CO CO
CH3I
CH3
CO I I-
Ir O
I CO
CO
CH3 CH3
CO I CO CO I CO
MeIr(CO)2I2 Ir Ir
I CO I CO
CO
Reproduced from Catal. Today, 2000, 58, 293-307
Regime 1: Favored at low ratios of MeI to Ir and at low [H20] and [I-].
Reaction rate is inversely proportional to PCO.
Major from of Ir is Ir(CO)3I
Regime 2: Observed at high [I-]

Major Ir species is [Ir(CO)2I2]-
Rate increases with increasing PCO and decreases with increasing [I-]
Kevin Shaughnessy
175
Regime 3: Observed under a variety of conditions, particularly at high [H2O] or [MeOH]

Major species is [HIr(CO)2I2]- which catalyzes both methanol carbonylation and the water-gas shift
reaction.
Comparison of the Rh and Ir systems: Model studies in aprotic solvents (J. Chem. Soc., Dalton
Trans. 1996, 2187):
- The Ir-CH3 bond is stronger than the Rh-CH3 bond due to relativistic effects of the heavier Ir center.
(Theoretical study: Organometallics, 2000, 19, 1973-1982)
CH3 L CH3
I CO CH3I I CO L I
M M M O
I CO kIr/k Rh= 120 I CO kRh/kIr = 105 I CO
I I
While oxidative addition to Ir is faster by 2 orders of magnitude than for Rh, the situation is reversed
for the migratory insertion step. For Rh, oxidative addition is rate limiting followed by very fast
migratory insertion. For Ir, the methyl complex can be isolated and only undergoes migratory
insertion upon heating under CO pressure. Under protic conditions, migratory insertion is greatly
accelerated for the Ir complex (Chem. Commun. 1995, 1045). Protic solvents facilitate dissociation of
iodide from [MeIr(CO)2I3]-, which occurs prior to migratory insertion.
Recent studies of the catalytic cycle have shown the key intermediate to be [MeIr(CO)3I2], which
undergoes migratory insertion much faster than [MeIr(CO)2I3]-. (Chem. Comm. 1998, 1023-1024)
CH3 CO CH3
I CO CO I
Ir Ir O
I CO I CO
L L
L = CO is 800 times faster than L = I at 85 ˚C under 400 psi CO in chlorobenzene.

L = CO: ∆H‡ = 89 kJ/mol, ∆S‡ = -36 J/mol•K
L = I-: ∆H‡ = 109 kJ/mol
Extrapolation of these results to 185 ˚C would predict that the neutral species would undergo
migratory insertion 9 times faster than the anionic species.
Pd-catalyzed carbonylation of aryl and vinyl halides

J. Tsuji, Palladium Reagents and Catalysts, Wiley & Sons, Chichester, 1995, Ch. 4
Pd(PPh3)4
CO, NuH, base O
X + HB+ X-
Nu
Kevin Shaughnessy
176
O
PPh3 B: Br
Nu
H Pd Br Pd(PPh3)2
NuH PPh3
HB+ Br-
PPh3
PPh3
O
Pd Br
Pd Br
PPh3
PPh3
CO CO
Pd Br
PPh3 PPh3 PPh3
Oxidative addition is followed by migratory insertion to give a palladium-acyl. Nucleophilic attack by

alcohols or amines on the carbonyl carbon results in formation of the organic product and a Pd-H that
rapidly decomposes. The mechanism for the nucleophilic attack is analogous to the mechanism for
nucleophilic attack on simple carboxylic acid derivatives.
This reaction is most commonly applied to the synthesis of esters and amides, but aldehydes and
ketones can be made in this way as well.
OR
ROH
Et3N
PPh3 O
O
RNH2 NHR
Pd Br
PPh3
HCO2H O
RSnBu3
Kevin Shaughnessy
177
2. Hydroformylation
Cobalt-based hydroformylation catalysts
Hydroformylation or the oxo process was originally developed by Roelen in the late 1930’s while working
for Ruhrchemie. The original catalyst was Co2(CO)8, which is still widely used. In the hydroformylation
reaction, the elements of formaldehyde (H and CHO) are added across a double bond to give an
aldehyde. Both linear and branched products can be produced, although the more desirable linear
aldehydes are usually the major products when using aliphatic olefins. Depending on the catalyst and
conditions, the aldehydes can be directly reduced to alcohols during the reaction.
Co(CO)8 O O
H2, CO reduction
R R
R R H H R OH OH
120 - 170 ˚C
200-300 atm
Catalytic cycle: Although the exact nature of some steps have not been conclusively determined, the
catalytic cycle is as follows.
O O
R
R H H
Co2(CO)8
O
O
H2 H2 R
H2 (OC)4Co
R Co(CO)4
+ CO HCo(CO)4 +CO
O O
-CO
+ RCH=CH2 R
R Co(CO)3 (OC)3Co
R H
Co(CO)3
Co(CO)4
R (OC)4Co R
+ CO
+CO
Co2(CO)8 undergoes hydrogenation to give the acidic “hydride” complex HCo(CO)8, which can also be
prepared directly and used as the catalyst.
The first step is a dissociative substitution of alkene for CO. Migratory insertion can result in either a
primary or secondary metal alkyl. Although this is the step that sets the regiochemistry of the products, it
Kevin Shaughnessy
178
is rapidly reversible. This rapid reversibility results in alkene isomerization and H/D exchange. Since ß-H
elimination requires an open coordination site, isomerization and isotope exchange are inhibited by
increased CO pressures.
The next step is a second migratory insertion to form the coordinatively unsaturated acyl that can
coordinate another CO to give the 18 electron acyl complex. Under standard catalytic conditions with 1-
octene, this is the only species observed by IR.
The mechanism of the hydrogenolysis step is less clear. One possible mechanism is the reaction with H2
to give the aldehyde and HCo(CO)4, which could occur by oxidative addition/reductive elimination
(unlikely due to the expected high activation barrier) or heterolytic H2 activation (s-bond metathesis). A
second possible mechanism would involve a dinuclear reaction with HCo(CO)4.
O
H2
R H
+ HCo(CO)3
O O
-CO
R Co(CO)4 R Co(CO)3
O
HCo(CO)4
R H
+ Co2(CO)7
Evidence for both mechanisms has been observed. HCo(CO)4 reacts 20-30 X faster with the Co-acyl
than H2 does at room temperature (Organometallics, 1986, 5, 209-215). Under the catalytic conditions,
the H2 concentration is about 2 orders of magnitude larger than that of HCo(CO)4. At the typical reaction
temperature (> 100 ˚C), the higher activation enthalpy of H2 cleavage than HCo(CO)4 cleavage will
become less significant. Therefore, it is accepted that under industrially relevant conditions, cleavage
occurs by H2 addition.
Regioselectivity: Generally the linear isomer is more valuable industrially than the branched isomer.
Since the catalytic cycle is irreversible, the observed regioselectivity represents the kinetic product ratio
rather than the thermodynamic preference. Generally the regioselectivity is not determined by the rate at
which alkene insertion occurs to give primary and secondary Co-alkyls. Rather the regioselectivity is
determined by the relative rate of migratory insertion of the primary and secondary alkyls to CO. Less
hindered alkyl groups migrate more rapidly than larger groups.
The regioselectivity can be modified by adding phosphine to the Co-catalyzed hydroformylation system.
This advance was discovered at Shell chemical. Using HCo(CO)3PBu3 as catalyst, higher
linear:branched ratios are achieved. This appears to be due to a greater degree of regiocontrol in the
initial migratory insertion of the alkene into the Co-H.
• Steric: Substituting PBu3 for CO increases the steric bulk of the metal center, which would be
expected to favor formation of a primary Co-alkyl.
• Electronic: Substituting PBu3 for CO significantly decreases the acidity of the cobalt-hydride.
Therefore, there is a lower preference for Markovnikov-type addition of H-Co to the alkene.
The Shell phosphine-modified catalyst is slower than HCo(CO)4, so higher temperatures are required for
acceptable rates. The phosphine-modified catalyst is more stable though, so it can run at lower CO
pressures.
Kevin Shaughnessy
179
Rhodium-based hydroformylation catalysts
Simple rhodium carbonyls are inactive for the hydroformylation reaction due to the formation of stable,
catalytically inactive Rh-carbonyl clusters occurs. HRh(CO)4 can be formed under high H2 and CO
pressures to give a very active catalyst, but it also isomerizes alkenes and gives low linear:branched
ratios.
Addition of phosphines to these rhodium systems dramatically improves both the chemo- and
regioselectivity, while maintaining high reaction rates of the initial Rh-carbonyls. This system has been
commercialized by Union Carbide.
(Ph3P)2Rh(CO)H
O
H2, CO
molten PPh3 H
100 ˚ C, 50 atm 92 % selectivity
The Rh-system is sufficiently more reactive than the Co-systems to offset the dramatic price difference
($Rh:$Co = ca. 300:1).
The generally accepted mechanism for the Rh systems is similar to that for the Co catalysts. It was first
proposed by Sir Geoffrey Wilkinson in 1968. (J. Chem. Soc. (A) 1968, 3133-3142)
H H
Ph3P OC
Rh CO Rh CO
Ph3P Ph3P
CO PPh3
O
R
H -CO
O
R H O
Ph3P Rh PPh3 Ph3P Rh PPh3 R H

R
CO CO
H2
R
CO R
R
Ph3P H
Rh R
Ph3P Ph3P
CO Rh Ph3P Rh PPh3
Ph3P
+ CO CO CO
R
Ph3P Rh PPh3
CO
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180
The key Rh complex is a 5-coordinate 18 electron species. Due to the high trans-effect ligands (CO, H),
the large phosphines occupy cis coordination sites. Both phosphines can be equatorial, or one can
occupy an axial position.
Dissociative substitution of alkene for CO proceeds through a 4-coordinate, square planar intermediate.
These catalyst have very high linear:branched ratios. Alkene migratory insertion largely determines the
regioisomeric ratio, because the square planar Rh-alkyl is rapidly trapped by CO in an irreversible
reaction under the reaction conditions. For a primary Rh-alkyl this is followed by CO migratory insertion
and then hydrogen cleavage. Secondary Rh-alkyls undergo CO insertion slowly, so alkene isomerization
products are also observed.
The strong kinetic preference for CO insertion to occur for primary Rh-alkyls can be very useful.
Industrially, alkenes can be prepared most economically as a thermodynamic mixture of alkene isomers.
These rhodium catalysts will hydroformylate both terminal and internal alkenes to predominately linear
aldehydes.
H2, CO
H2, CO Rh H2, CO
Rh slow Rh
fast slow
O
O
H
H
Improved linear to branched ratios are obtained using chelating phosphines with large bite angles.
Texas-Eastman has commercialized hydroformylation processes using ligands such as BISBI that give
linear:branched ratios of 96:4 under mild conditions and low L:Rh ratios. (U.S. patents 4,694,109 (1987)
and 4,879,416 (1989)) BISBI (ßN = 113˚) gives a much more regioselective catalyst than dppe (ßN = 86
˚). Substituting the diphenylphosphino group for a dibenzophosphole increases the regioselectivity to
99.4:0.6, although catalyst stability is a problem (U.S. Patent 5,332,846 (1994). Union carbide has
developed bis(phosphite) ligands that also show very high linear:branched ratios (96:4) even when
starting with 2-butene.
MeO t-Bu
O
P
PPh2 P O
O
P O
PPh2 P O
O
MeO t-Bu
BISBI
Eastman Kodak
Eastman Kodak Union Carbide
To what degree does the bite angle affect the linear:branched ratio as well as the catalytic activity in
these systems? Piet van Leeuwen has developed a class of ligands that provide highly active
Kevin Shaughnessy
181
hydroformylation catalysts. They can also be easily modified to adjust either the bite angle or the electron
donating ability of the ligand. (Organometallics, 2000, 19, 872-883)
O
PAr2 PAr2
Me2 Bn
Si N
O O O O
PPh2 PPh2 PPh2 PPh2 PPh2 PPh2 PPh2 PPh2 PPh2 PPh2
1 2 3 4 5
102.0˚ 108.5˚ 111.4˚ 114.1˚ 120.6˚
Hydroformylation of 1-octene at 80 ˚C
Ligand l:b ratio % linear TOF

aldehyde (mol/mol Rh•h)
1 8.5 88.2 36.9
2 24.2 94.4 76.5
3 52.2 94.5 187
4 50.6 94.3 154
5 50.2 96.5 343
Increasing bite angle improves the linear:branched ratio and has an even more significant improvement
on the TOF of the catalyst. How does the bite angle affect both regioselectivity and TOF?
It has been hypothesized that bite angle might affect the equilibrium between the diequatorial (ee) and
equatorial-axial (ea) L2Rh(CO)2H complexes, but van Leeuwen sees no correlation between bite angle
and the ee:ea ratio. There also does not seem to be any relationship between bite angle and the rate of
CO dissociation from L2Rh(CO)2H.
The increase in the linear to branched ratio is likely a steric effect. As the bite angle increases, the
chelating phosphine should crowd the neighboring ligands. This would result in an increased preference
for alkene insertion to give a less sterically demanding primary Rh-alkyl.
The effect of bite angle on the TOF is less clear. Numerous steps in the cycle could be affected by
changes in the bite angle. Based on their data, van Leeuwen offers two possible explanations.
1) Increased stability of the square-planar L2Rh(CO)H intermediate with increasing bite angle. Due
to steric strain, the trans square-planar complex should be more stable than the cis-isomer.
Therefore, ligands with large bite angles may be able to better accommodate the more stable
trans-chelate. Stabilization of the square-planar intermediate will increase it’s equilibrium
concentration. Since the reaction rate (TOF) is directly related to the concentration of this
species, increasing it’s equilibrium concentration should result in higher TOF values.
Kevin Shaughnessy
182
H P
P
Rh CO OC Rh H
P
CO P
2) Increasing the bite angle is expected to accelerate migratory insertion of the alkene, as well as
the subsequent insertion of CO. As the bite angle gets larger, the chelating ligand becomes more
sterically demanding. Migratory insertion lowers the coordination number at the metal, so it
reduces the steric strain.
R
H P R
P
Rh OC Rh
P
CO P
Aqueous-Phase Hydroformylation
Because of the very high price of Rh, a way to efficiently recycle the catalyst was desired. In the 1970s,
Rhône-Poulenc commercialized an aqueous-phase process based on a catalyst derived from Rh/TPPTS
(TPPTS = triphenylphosphine trisulfonate).
[Rh(cod)(µ-Cl]2
TPPTS
CHO +
CHO P
CO/H2 40 bar
3
80°C, H2O 95% 4%
SO3Na
TPPTS
Propene has low solubility in water, but is sufficiently soluble to give good rates of conversion. The
butanal product has low solubility in water and forms an immiscible phase. The butanal can be decanted
off and the aqueous Rh solution reused. Industrial systems can be used for months before requiring a
new charge of catalyst. Because of the low solubility of higher alkenes (i.e., 1-octene) in water, this
system gives very low conversion. The use of surfactants or ligands that are surface active can improve
the reactivity of these higher olefins. (Chem. Rev, 2009, 109, 643).
decant
propene,
butanal CHO
CO, H2 heat
Rh/TPPTS Rh/TPPTS
H 2O H 2O
propene, H2, CO
Asymmetric Hydroformylation
Asymmetric hydroformylation requires that the catalyst exhibit both high regioselectivity and
enantioselectivity. Moreover, the necessary regioselectivity is opposite to that typically desired. As such,
generally, the systems are only useful in hydroformylation of styrene derivatives.
Kevin Shaughnessy
183
Initial work focused on Pt based catalysts modified with SnCl2 in the presence of chiral diphosphines.
Although these systems offer high enantioselectivity, they suffer from poor regio- and chemoselectivity.
LPtCl2
SnCl2 CHO
H2, CO CHO
Ph2P
O PAr2 PPh2
N PAr2
PAr2
O PAr2 BOC
70 % ee 90 % ee 85 % ee
PAr2 = dibenzophosphole
Rh-based systems have been reported with high enantioselectivity and improved regioselectivity. (J. Am.
Chem. Soc. 1993, 115, 7033; Chem. Comm, 1994, 395; Tetr. Lett. 1994, 35, 2023) Similar ligands have
been developed by Union Carbide (WO 93/03839 (1993)).
LRh(CO)2H CHO PPh2

H2, CO CHO
O
P
O
O
95 % ee
86:14 branched:linear
Kevin Shaughnessy
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13-Insertion Polymerization and Oligomerization of Alkenes, Part 1: Early Transition Metals
Metal-catalyzed (insertion) polymerization of alkenes has become a massive business, supplying plastics
for a wide variety of uses. Global polyolefin production (polyethylene and polypropylene) was 113 million
tons in 2009
Material Production in 2009 Applications

(millions of tons)
Polyethylene
Low Density (LDPE): Radical 18.1 Flexible, resilient material: plastic
polymerization, highly branched bags, bottles, tubing, lab equipment
Linear Low Density (LLDPE) : 19.2 Very flexible, stretchable: plastic wrap
Ziegler Natta catalysts (saran), plastic bags/sheets
High Density (HDPE) : Ziegler 30.5 Strong, rigid material: fuel tanks,
Natta catalysts, often folding tables/chairs, water pipes,
ethylene/1-alkene copolymer plastic lumber, hard hats
Polypropylene: Ziegler Natta 45.2 Tough, flexible, colorfast: engineering
catalysts plastic, Rubbermaid containers,
carpets/rugs
Heterogeneous Olefin Polymerization Catalysts: The Ziegler-Natta systems.
History of insertion polymerization: Frank McMillan, “The Chain Straighteners: The Discovery of
Linear and Stereoregular Polymers, MacMillan Press, London, 1967.
K. Ziegler (Angew. Chem., 1952, 64, 233): Ziegler was originally studying the Aufbau reaction, which
uses trialkyl aluminum compounds to make oligomers from ethylene. Ziegler found that adding transition
metals salts resulted in significant changes in the reactivity.
AlR3 + R AlH3 + 3
Al R
n mixture of
Ni/AlR3 1-alkenes
ZrCl4/AlR3
polyethylene
TiCl4/AlR3
polyethylene "Es geht in Glas!"
low pressure
This was a heterogeneous process. Insoluble metal salts and trialkylaluminum species were mixed in a
hydrocarbon solvent under ethylene pressure.
G. Natta (J. Am. Chem. Soc., 1955, 77, 1708): Soon after, Natta showed that the Ziegler catalyst would
polymerize propylene to give polypropylene.
Kevin Shaughnessy
185
TiCl4/AlR3
CH3 40 % crystalline material
n
α−TiCl3/AlR3
CH3 90 % crystalline
n
3/1 helix
X-ray and IR studies showed that the crystalline material had the same configuration at each chiral
center. The polymer was isotactic, (vide infra) and existed as a 3/1 helix in the solid-state.
Ziegler and Natta shared the 1963 Nobel Prize in chemistry for their contributions.
Aside: Polymer Stereochemistry
Polymers, such as polypropylene, are often classified by the relative stereochemistry of the side-chains
along the polymer backbone. The major classes of stereochemistry are: atactic, isotactic, and
syndiotactic
Atactic
Isotactic
Syndiotactic
The microstructure of polypropylene is most conveniently analyzed using 13C NMR.
r m m r m r
13C NMR shift is sensitive to the two
stereocenters on either side on mmrm pentad
spectrometers > 300 MHz. This is
called pentad resolution.
Kevin Shaughnessy
186
Heterogeneous Ziegler-Natta systems are still widely used in industry, but from the beginning there was
interest in developing homogenous, single-site catalysts for olefin polymerization. These were desired
both as model compounds for mechanistic studies and to provide more consistent and tunable catalysts.
We will discuss this in detail later.
The major problems with heterogeneous systems are:
- There are a variety of different catalytic sites with different activity producing polymers with
different molecular weights and tacticities. The polymers produced are always blends.
- Heterogeneous systems are difficult to tune, because there is not much that can be varied and
they are generally poorly understood. Although fairly selective systems have been developed,
the work is largely empirical.
The major advantage is that they are heterogeneous and can be used under industrially desirable
conditions either in the gas phase or as suspensions.
Mechanism of Alkene Polymerization:
Kevin Shaughnessy
187
n
R R R'
[M] R' R' [M]
[M]
kinit kp n+1
R' = H, alkyl R R R
kt1 kt2 kt3
[M] R' + polyolefin
Molecular weight is determined by the ratio of the rate of propagation vs. the rate of chain transfer.
kp
Mw =
∑k tn
Initiation:
€ The active species is believed to be a coordinatively unsaturated metal alkyl formed by reaction of the
metal halide salt with the alkyl aluminum species.
+
Cl RAlX2 R R R
M M + ClAlX2 M M
Cl X = R, Cl AlCl2X2
Cl
Cl AlClX2
Propagation:
The exact nature of the propagation step was controversial for some time. Cossee proposed a
mechanism involving simple migratory insertion of an alkene into a metal alkyl (Tetrahedron Lett., 1960,
1(38) 12-16).
P P M
M M
P
= open coordination site
Green, and Rooney proposed an alternative mechanism based on an a-elimination to give a carbene.
Since there were few examples of isolated alkene alkyl complexes that undergo migratory insertion, they
felt that an alternative mechanism was necessary. Formation of a metalacycle followed by reductive
elimination gives a new metal-alkyl. (J. Chem. Soc., Chem. Comm., 1978, 604)
H H H
P M M
M
P P
H P M
M
P
Kevin Shaughnessy
188
The major difference between the two mechanisms, should be in the kinetic isotope effect. The Green
Rooney mechanism would require a large kinetic isotope effect (ca. 3).
Grubbs carried out two sets of experiments to probe the isotope effect in models for the Z-N systems.
Grubbs first carried out the polymerization of a mixture of ethylene and ethylene-d4. (J. Am. Chem. Soc.,
1982, 104, 4479) No isotope effect was observed, however this result did not definitively rule out an a-
elimination mechanism.
Cp2TiCl2
H H D D EtAlCl2
+ polyethylene
H H D D kH/kD = 1.04
Since this experiment was inconclusive, Grubbs designed a stereochemical probe to determine if an a-
H/D agostic interaction affected the insertion process. The Cossee mechanism should give a nearly 1:1
mixture of diastereomers, since there is no primary isotope effect in this mechanism. The Rooney-Green
mechanism would be expected to give a unequal product distribution. A 50:50 diastereomeric ratio of
products was produced in the reaction. (J. Am. Chem. Soc., 1985, 107, 3377)
DH EtAlCl2 H D
-78 ˚C D H
Cp2Ti TiCp2
Cp2Ti
Cl
H D
D H
Cp2Ti TiCp2
H H
D D
H H
Cp2Ti Cp2Ti
Cl Cl
H D D
D D H
Cp2Ti H H H H TiCp2
Cp2Ti Cp2Ti
Cl Cl
Other systems have shown that there is a KIE (Angew. Chem. Int. Ed. 1990, 29, 1412).
Kevin Shaughnessy
189
+ +
D D
n-Bu n-Bu
Cp2Zr
Cp2Zr
H
H
H +
CH2Bu +
D CH2Bu H D
Cp2Zr Cp2Zr
n-Bu n-Bu
D D
H + +
CH2Bu D H CH2Bu
H2 H2 CH2Bu
DH2C Cp2Zr CH2Bu Cp2Zr
D D DH2C
D
Bu D n-Bu D n-Bu Bu
1:1.30
These observations have led to the modified Green-Rooney mechanism that involves an α-agostic
interactions rather than α-elimination (Organomet. 1992, 11, 4036; Angew. Chem. Int. Ed. 1990, 29, 279).
Grubbs and Coates suggest that high activity catalysts do not need the α-agostic assistance, while less
reactive complexes do and show a isotope effect (Acc. Chem. Res. 1996, 29, 85).
P
H P
P M
M P M H
H
M
Chain Transfer:
A variety of chain transfer mechanisms have been identified by modeling studies.
ß-H elimination
H ß-H H
[M] + [M]-H
n n
R R R R
Hydrogenation
H H2 H
[M] H + [M]-H
n n
R R R R
Chain transfer to aluminum
H R2Al-CH3 H
[M] R2Al + [M]-CH3
n n
R R R R
Kevin Shaughnessy
190
Chain transfer to monomer

H H H
[M] + [M]
n n
HR R R R R
R
ß-R elimination
H ß-R H
[M] + [M]-R
n n
R R H R
Homogeneous Ziegler-Natta-type polymerization catalysts
The first homogeneous systems were based on metallocene dichlorides, and were designed to mimic the
activation process believed to occur in the heterogeneous systems.
+
Cl RAlX2 R R R
M M + ClAlX2 M M
Cl X = R, Cl AlCl2X2
Cl
Cl AlClX2
+
Cl RAlX2 R R R
Cp2M Cp2M + ClAlX2 Cp2M Cp2M AlCl2X2
Cl X = R, Cl Cl
Cl AlClX2
M = Ti, Zr, Hf
These systems would polymerize ethylene, but slowly. Propylene and other higher alkenes could not be
polymerized. The major advance was the introduction of the activator methylaluminoxane (MAO) by
Kaminsky (Macromol. Chem. Rapid. Comm., 1983, 4, 417)
Cl
Zr
Cl
MAO
atactic polypropylene
H3C Activity: 106 g/mol Zr•bar•h
Mw/Mn = 1.5 - 2.5
MAO was the magic ingredient that provided much more active catalysts than were obtained with typical
alkylaluminum Lewis acids. MAO is a poorly defined mixture of linear and cyclic oligomers produced by
the controlled hydrolysis of trimethylaluminum.
Kevin Shaughnessy
191
H3C O
- 2 CH4 Al
AlMe3 + H2O O O +
Al Al n
CH3 CH3 O Al
CH3
Al O
CH3 n
MAO acts as both an alkylating agent and a Lewis acid to form the catalytically active, 14 electron
zirconocene-methyl cation.
X CH3 X
CH3
Cp2M + Al O Cp2M + Al O
X n X n
CH3
X
Cp2M L CH3 + X -
Cp2M Al O
X X L n
Al O
n
MAO is typically used in large excess (1000 – 10000:1 Al:Zr) to ensure activation of the catalyst and
destruction of catalyst poisons (water, oxygen, etc). Although widely used, it’s complex nature and the
need to use a large excess led to the development of monomeric reagents that could produce the
necessary cationic complexes.
The cationic metallocene-alkyls are extremely strong Lewis acids. Very weakly coordinating anions must
be used to ensure that they exist as separated ion pairs. Common “non-coordinating anions” such as
BF4-, PF6-, or SbF6- form fluoride bridged adducts and/or lose F-. The best systems are based on
fluorinated triarylboranes or tetraarylborates. (Review: Marks, Chem. Rev., 2000, 100, 1391-1434)
Protonation: Turner and Hlatky, US Patent 4,752,597 (1988); Turner, J. Am. Chem. Soc, 1989,
111, 2728; Bochmann, Angew. Chem. Int. Ed., 1990, 780; Bochmann, J. Organmet. Chem., 1992,
C5
-2 CH4 Cp* H
BPh3
Cp*2ZrMe2 + [R3NH]+[BPh4]- Zr
Cp*
F F
CH3 + -
-CH4
Cp*2ZrMe2 + [R3NH]+[B(C6F5)4]- Cp*2M B F
NR3 3
F F
Kevin Shaughnessy
192
Alkyl Abstraction: Marks, J. Am. Chem. Soc., 1991, 113, 3623; Ewen, Eur. Pat. 0427697
(1991); Chien, J. Am. Chem. Soc., 1991, 113, 8570.
+
Cp* Cp*
CH3 S CH3
Cp*2ZrMe2 + B(C6F5)3 Zr Zr [MeB(C6F5)3]-
C B(C6F5)3 S
Cp* H3 Cp*
+
Cp*
S CH3
Cp*2ZrMe2 + [Ph3C]+ [B(C6F5)4]- Zr B(C6F5)4]- + Ph3CCH3
S
Cp*
With the development of active homogenous catalysts that could polymerize 1-alkenes (i.e., propylene),
efforts were made to rationally design catalysts that would give specific tacticities. (Reviews: Chem. Rev.
2000, 100, 1223; ibid, 1253)
Cl
Zr
Cl
MAO Isotactic polypropylene

(EBTHI)ZrCl2
> 95% isosteric sequences
H3C n
Ewen, J. Am. Chem. Soc., 1984, 106, 6355; Kaminsky and

Brintzinger, Angew. Chem. Int. Ed. Engl., 1985, 24, 507.
Cl
Zr
Cl
MAO Syndiotactic polypropylene

> 95%heterosteric sequences
H3C n
Ewen, J. Am. Chem. Soc., 1988, 110, 6255
Origin of Stereocontrol:
Mechanisms for stereocontrol in polymerization reactions:

1) Chain-End control: The last monomer inserted (or sometimes the penultimate one) controls the
stereochemistry of the next insertion
2) Enantiomorphic Site Control: Topology of the catalyst determines the stereochemistry
Purely isotactic polypropylene would give only the mmmm pentad, but there are always errors. The types
of errors can determine what the mechanism of stereocontrol is.
Kevin Shaughnessy
193
These two mechanisms can be differentiated by analyzing the microstructure of the polymer.
Chain end control

Errors:
mmmr
mmrm
m m m m r m m m m
Site control
Errors:
mmrr
mrrm
m m m m r r m m m
Metallocenes typically operate under enantiomorphic site control. This raises the question of how the
chiral ligand set controls enantioselectivity. Unfortunately, polypropylene is not optically active, so model
studies must be carried out. Zambelli (Macromolecules, 1987, 20, 1015-1018) and Pino (J. Am. Chem.
Soc., 1990, 112, 4911-4914) looked at the insertion of alkenes into chiral, resolved Zr-alkyl and Zr-H
species.
H M M M
H3C
H3C
Predominant re and si Predominant
si insertion insertion re insertion
Thus, the chiral ligand appears to control the conformation of the alkyl chain. The incoming alkene
orients itself opposite the alkyl chain. Since the catalyst has C2-symmetry, insertion from either side
should give the same re insertion (i.e., the coordination sites are homotopic).
re insertion
P
H H
M M
H H
P
re insertion
The syndiotactic selectivity of Ewen’s Cs-symmetry catalyst can be explained in the same way. Since this
complex has a mirror plane of symmetry, the two coordination sites are enantiotopic.
Kevin Shaughnessy
194
si insertion
P P
M M
H H
H H
re insertion
C1-symmetry can give a range of tacticities depending on the exact structure.
CH3
M M M
Cl Cl Cl Cl Cl Cl
MAO MAO H3C MAO

H3C H3C
Syndiotactic Hemiisotactic Isotactic
Recent research has looked to move beyond metallocenes to other ligand architectures that are easier to
make and modify and that offer unique activity or selectivity. (review of phenoxy-imine and related
catalysts). Chem. Rev. 2011, 111, 2363)
Kevin Shaughnessy
195
t-Bu
R
Ti C6F 5 O t-Bu
Me 2Si N R
N N O
M C6F 5 S R
t-Bu R R M
Constrained Geometry O S R
Dow O
t-Bu
M = Ti, Zr, Hf
Phenoxy-Imine catalysts
Coates, Fujita t-Bu
Symyx
Kevin Shaughnessy
196
13-Insertion Polymerization and Oligomerization of Alkenes, Part 2: Late Transition Metals
It had long been thought that late transition metals could not polymerize simple alkenes, such as
ethylene.
kins
R H kß-H H
LnM LnM LnM
R R
Most late transition metal complexes undergo migratory insertion (kins) slowly and ß-H elimination rapidly
(kß-H). In contrast highly electrophilic early transition metals have fast insertion rates and relatively slow ß-
H elimination rates. The ratio of the rates largely determines whether dimers, oligomers, or polymers are
produced.
• Kins << kß-H: Dimerization
• Kins ≈ kß-H: Oligomerization
• Kins >> kß-H: Polymerization
Dimerization
Many late transition metal complexes, particularly d8 metals, will dimerize ethylene or 1-alkenes.
Ethylene dimerization is not industrially useful, but dimerization of higher alkenes can be. Dimerization of
propylene can give a multitude of products. 2,3-Dimethyl-2-butene is useful as an anti-knock additive to
gasoline.
Ni
Ni-H
Ni
Plus olefin isomers
(hfacac)2Ni
PCy3
MAO
EtAlCl2 + other C6, C9, and C12+ isomers
J. Organomet. Chem. 2001, 622, 286 64 %
Oligomerization of Ethylene:
A variety of Nickel catalysts can be used to oligomerize ethylene into mixtures of higher alkenes. This
chemistry is part of the Shell Higher Olefin Process (SHOP), which converts ethylene to alkenes, which
can be sold or converted to long chain aldehydes or alcohols by hydroformylation.
Kevin Shaughnessy
197
The Ni complex used in the SHOP process is a P-O anionic chelate that can be prepared in situ from the
ligand and (COD)2Ni.
Ph2 Ph2
O P P H
-COD -COD
Ph2P + Ni(COD)2 Ni H Ni
OH O O O
O
Ph2
P H
Ni n CH2CH2
O O
Ph2 Ph2
P H P H
Ni Ni
O O O O
n-1
n-1
Ph2
P H
Ni
O O n-1
This catalyst is very selective for the production of linear 1-alkenes (> 98 %). A Schulz-Flory distribution
of alkene oligomers is produced.
A related class of Ni complexes are formed starting from a phosphorous ylide. These catalyst typically
give higher molecular weight products, and in some cases can give polyethylene.
Ph2
O P PPh3
Ni(COD)2
Ph3P Ni
R PPh3 R O Ph
Chromium-based catalysts are able to produce 1-hexene with very high selectivity, rather than the
statistical distribution seen with the nickel-based systems (i.e. Chem. Commun. 2002, 858).
CrCl3·3H2O
Ligand
MAO
3 1 X 106 g/g Cr·h
80 ˚C, 20 bar > 90 % 1-hexene
CH3
N
Ligand = P P
2 2
OMe MeO
Kevin Shaughnessy
198
The mechanism of this oligomerization is different from the nickel case, in that it proceeds through a
Cr(III) metallacycle (Bercaw, JACS, 2004, 126, 1305). This mechanism is the key to the selectivity. The
metallacyclopentane cannot easily undergo b-hydride elimination to give 1-butene. In contrast, the
chromocycloheptane undergoes b-hydride elimination faster than insertion of another ethylene.
LnCrI 2
LnCr LnCr
H
LnCr
A group at Sasol has shown that by changing the ligand to (Ph2P)2Ni-Pr that the catalyst can be made to
selectively make 1-octene (> 70% selectivity).
Ethylene Polymerization
Because of the slow rates of alkyl migration for most late-transition metal complexes, it was long thought
that high molecular weight polymer could not be produced. Maurice Brookhart (UNC) has shown that this
is not the case as long as electrophilic late transition metal complexes are used as the catalysts. Review:
Chem. Rev., 2000, 100, 1199-1203
polyethylene
Co
Mw = 40,000
L
H H
H
At low temperature (-70 ˚C) the polymerization reaction can be observed by 1H NMR (J. Am. Chem. Soc.,
1985, 107, 1443-1444). The ethylene alkyl species cannot be observed, but the growing polymer chain is
observed as an equilibrating mixture of ß-agostic species.
Kevin Shaughnessy
199
+ +
HBF4
Co Co Co
L L L
H H H J = 61 Hz
H
+ + +
nH2C=CH2
Co Co Co
L L L
H H H H CH3
n
3 upfield signals in 1H NMR 8:20:80
Co Co H
L L R
H R H H
H H
Although this system is much slower than Ziegler-Natta-type catalysts, it showed that under certain
circumstances late transition metals could polymerize alkenes.
• Requires highly electrophilic metal center (cationic metal with “non-coordinating anion”)
• π-acidic ligands help to give an electrophilic metal center.
Pd and Ni diimine based systems:
In the late 90’s Brookhart and collaborators at DuPont developed a class of nickel and palladium catalysts
that would polymerize ethylene to high molecular weight polyethylene. (JACS, 1995, 117, 6414)
i-Pr Me Me i-Pr
N N
Ni
i-Pr i-Pr
Br Br
MAO branched polyethylene (50 branches/1000 C's)
Mw =80,000
toluene, 0˚C 3 X106 g/mol Ni•h
Kevin Shaughnessy
200
i-Pr Me Me i-Pr
N N
Pd
i-Pr i-Pr
L Me
CF3 -
4
CF3 highly branched polyethylene (100/1000 C's)
Mw =10,000
CH2Cl2, 25 ˚C 20 kg/mol Pd•h
Catalyst activity and polymer molecular weight were strongly dependent on the steric bulk of the ortho
substituents on the aromatic rings. When the substituent was methyl instead of isopropyl, the molecular
weight of the polymer dropped by an order of magnitude. The productivity was also an order of
magnitude lower with the methyl substituent.
These catalysts were unique because they produced highly branched polyethylene rather than linear
polyethylene, particularly for Pd. Interestingly, use of hexane as the monomer gave a very similar
polymer as ethylene. Nickel gave lower branching ratios, although the amount of branching could be
greatly varied.
The high degree of branched suggested a “chain walking” mechanism. Thus, ß-hydride elimination is
competitive with, if not faster than, migratory insertion, yet high molecular weight polymer is produced.
Therefore, displacement of the polymer chain by ethylene (C to A) must be slow.
Unlike early transition metal, Ziegler-Natta polymerization catalysts, the alkyl olefin complex can be
observed. For both the Ni and Pd systems, this is the resting state. The rate determining step is
migratory insertion. Therefore the reaction rate is independent of [ethylene]. At low temperature, Ni and
Pd alkyl ethylene complexes can be prepared and the rate of migratory insertion measured using NMR.
(Pd: J. Am. Chem. Soc., 1995, 117, 6414-6415. Ni: J. Am. Chem. Soc., 1999, 121, 10634-10635)
Kevin Shaughnessy
201
Chain transfer (kct)
R=H
migratory insertion
kins
+ ß-hydride elim. +
N R + N H N H
Pd Pd Pd
N N R N R
B 1,2-insertion
A C
2,1-
inserti
on
R' + R +
N R' + Chain walking
N
Pd CnH2n+1 N Pd
N Pd CnH2n+1
H N H
N
D
Cn branch
Theory gives good agreement with the experimental values. The theoretical analysis of the Ni systems
suggests that bulky ligands lower the migratory insertion barrier by destabilizing the resting state
complex. Bulky ligands also greatly increase the barrier to chain transfer by destabilizing the transition
state for this process. The barrier is approximately double to that determined computationally for a
sterically unhindered complex. (Ziegler, J. Am. Chem. Soc. 1997, 119, 1094-1100 and 6177-6186)
Complex Propagation Branching Termination
2,6-di-i-Pr 13.2 15.6 18.2
no aryl 16.8 12.8 9.7
Brookhart initially proposed that the large steric bulk of the ortho-substituents on the aromatic rings
inhibited associative displacement of the polymer chain from C.
Kevin Shaughnessy
202
+ +
i-Pr i-Pr i-Pr i-Pr
N N N N
Pd Pd
H
i-Pr i-Pr i-Pr H i-Pr
R
R
R
+ +
i-Pr i-Pr i-Pr i-Pr
N N N N
Pd Pd
H
i-Pr H i-Pr
i-Pr i-Pr
Ziegler has suggested a variation on this mechanism in which hydride is directly transferred from the ß-
carbon of the polymer chain to coordinated ethylene. This mechanism was proposed since no stable
olefin hydride species could be identified.
+ +
i-Pr i-Pr i-Pr i-Pr
N N N N
Pd Pd
i-Pr i-Pr i-Pr H i-Pr
H
P R
+ +
i-Pr i-Pr i-Pr i-Pr
N N N N
Pd Pd
i-Pr H3C i-Pr i-Pr P H3C i-Pr
Propagation P
Kevin Shaughnessy
203
Olefin/CO Alternating Polymerization
Palladium complexes catalyze the perfectly alternating polymerization of CO and alkenes. (Review:
Chem. Rev. 1996, 96, 663-681).
The polymer is produced by sequential migratory insertion of CO and alkene. The perfect selectivity is
due to the unfavorable thermodynamics of sequential CO insertion and the slow insertion of alkene into a
Pd-alkyl species.
O O
R COR
LnPd LnPd
CO CO L
CO
O
O
R R
LnPd LnPd
CO
resting
state
LnPd
O R
O O
slow
LnPd n
R LnPd R
CO
Kevin Shaughnessy
204
Initiation: Analysis of polymer end groups suggest that there are two initiation pathways involved under
normal conditions. 1) Formation of a Pd-acyl species. 2) Insertion of an alkene into a Pd-hydride.
Pd-Carbomethoxy Initiation
2+
LPd CO CH3OH
H+
O + +
LPd2+
LPd OMe LPd
O
CH3OH OMe
+
H+ LPd OMe CO
Pd-H Initiation
+ O + +
CO
LPdH+ LPd LPd
LPd O
H
Termination: Similarly, there are two likely chain transfer mechanisms involved.
Protonolysis
O + O
CH3OH
LPd P LPdOCH3+ + H3C
P
Methanolysis
O + O
CH3OH
LPd P LPdH+ + MeO P
Thus three different polymeric products can be produced:
1. A diester: Pd-CO2Me initiation and methanolysis chain transfer

2. A diketone: Pd-H initiation and protonolysis chain transfer
3. A keto-ester: Can be produced either by Pd-CO2Me initiation and protonolysis chain transfer or
Pd-H initiation and methanolysis termination
At higher temperatures a mixture of all three types of products are produced, suggesting that both
pathways are viable and that crossover can occur. At lower temperature, only keto-esters are formed.
Kevin Shaughnessy
205
H H CH3OH
Diketone n O
+
LPd H
CO O +
+
LPd OMe Keto-ester
LPd H
O n
H OMe
O + n n CO
CH3OH
O n C2H4
LPd OMe CH3OH
MeO H +
O + n
LPd
LPd OMe H
n CO n LPdH+
n C2H4
O
O +
CH3OH MeO
LPd OMe
OMe
n O n
O Diester
Kevin Shaughnessy
206
14-Alkene and Alkyne Metathesis
Alkene metathesis is the metal-catalyzed disproportion of alkenes. This reaction has been known for
nearly 60 years, but only in the past 15-20 years has it become widely used in both industrial and
academic labs for the synthesis of polymers and complex organic compounds. The 2005 Nobel prize
was award to Yves Chauvin, Richard Schrock, and Robert Grubbs for their work in developing olefin
metathesis into a widely used process.
There are several classes of olefin metathesis reactions.
Cross Metathesis
(CM or XMET) 1
R
1 R +
2 R R2 +
Ring Closing Metathesis

R (RCM)
+
R
Ring Opening Metathesis n
n
(ROM)
Ring Opening
Metathesis Polymerization
(ROMP)
n
Acyclic Diene
Metathesis m
Polymerization n
(ADMET)
n
- m H2C=CH2
All of the above reactions are reversible, so equilibrium mixtures are obtained. To produce high yields of
a given product a suitable driving force must be present.
• Cross metathesis: Mixtures of products are produced unless a volatile byproduct (ethylene) is
produced that can be removed from the reaction mixture. The alkenes must also have different
reactivity in order to get selective cross-metathesis (J. Am. Chem. Soc, 2003, 125, 11360).
Olefin Type Grubbs Gen 2 Grubbs Gen 1 Schrock
Type I terminal alkenes, terminal alkenes, allyl terminal alkenes,
fast homodimerization wide range of allylic silanes, allylic allyl silanes
species, styrenes alcohols ethers and
esters, allyl halides
Type II styrenes with large o- styrene, 2° allylic styrene, allyl
slow subst., electron alcohols, vinyl stannanes
homodimerization deficient alkenes, 2° dioxolanes, vinyl
and 3° allylic alcohols boronates
Kevin Shaughnessy
207
Type III 1,1-disubstituted vinyl siloxanes 3° allyl amines,

no homodimerization alkenes, non-bulky acrylonitrile
trisubst. alkenes,
vinyl phosphonates,
4° allylic carbons,
protected 3° allylic
alcohols
Type IV nitro alkenes, 1,1-disubstituted 1,1-disubstituted
spectators to CM trisubstituted alkenes, disubst. alkenes
protected allylic enones, 4° allylic
alcohols carbons,
perfluorinated alkyl
alkenes, 3° protected
allyl amines
Reactions between two Type I alkenes: statistical mixture

Reactions between two alkenes of the same type (not Type I): non-statistical mixture
Reactions between alkenes of different types: selective CM
• RCM is favored for the production of unstrained rings and is driven both entropically and by the
elimination of a volatile alkene.
• ROM is only favored at very high olefin concentrations, or more commonly with strained olefins.
The same general features will hold true for the polymerization reactions.
Olefin metathesis was discovered in the 1950’s about the same time as Ziegler-Natta olefin
polymerization. The catalysts used from this time through the 80’s were poorly defined combinations of a
metal salt and main-group organometallic species. (i.e., WCl5/Bu4Sn or MoCl2(NO)2(PPh3)2/Al2Me3Cl3.
These types of catalysts are still used industrially.
Metathesis in the Shell Higher Olefin Process (SHOP)

C2H5 C11
C7H15 cat C7H15
C7H15 + C2H5 +
C4H9
C4H9
non C10-C14 fraction C7H15 C13
from ethylene oligomerization
Commercial synthesis of house fly pheromone

cat C13H27
C8H17 C13H27 C8H17 + + other products
Mechanism:
The mechanism of the reaction was disputed for a long time. One of the early proposals by Chauvin
turned out to be correct, but was not accepted for some time. He proposed a [2+2] reaction between a
metal carbene and the alkene to give a metalacyclobutane. Retro [2+2] would give the metathesis
products. (Makromol. Chem., 1970, 141, 161) His early contribution was the reason he was awarded the
Nobel prize.
R
R
LnM R' LnM CH2 + R R'
LnM R'
Kevin Shaughnessy
208
When this mechanism was proposed there was no precedent in the organometallic literature to support it.
Metal-carbenes without π-donor substituents (Schrock-type) had not been observed, and there was no
precedent for a [2+2] cyclization to give a metalacyclobutane. Pericyclic reaction theory tells us that a
concerted [2+2] reaction is not thermally allowed, although this applies for atoms with s and p orbitals
only.
An alternative mechanism, the pair-wise mechanism, was supported by many researchers.
RHC CHR'
M
RHC CHR'
R R' or 2 R R'
R R' R R'
R R'
M
Crossover experiments have been used in an effort to distinguish between these mechanisms. Since a
metathesis catalyst continues to scramble olefins through the reaction, it is important to design an
experiment that will let you look at the initial products.
H2C CH2 D2C CD2

Mo(NO)2Cl2(POct3)2
Al2Me3Cl3 H2C CH2
H2C CD2
D2C CD2
J. Am. Chem. Soc., 1976, 98, 2519
Well-defined catalysts
With the acceptance of the Chauvin mechanism, metal-carbene complexes were explored for their ability
to catalyze olefin metathesis.
The first active, well-defined system was (OC)5W=CPh2 (Tetr. Lett., 1976, 17, 4247). This complex would
polymerize cyclic olefins with modest activity and high selectivity for cis-alkene polymers.
Ph
(OC)5W Ph
Ph
Ph n
Mw = 440,000
95 % cis alkenes
Today there are two major classes of metathesis catalysts that are widely used. A molybdenum carbene
developed by Schrock (Tetrahedron, 1999, 55, 8141-8153) and a ruthenium carbene developed by
Grubbs (Acc. Chem. Res., 2001, 34, 18-29). Both compounds are now commercially available and have
been applied to a wide range of synthetic problems.
Kevin Shaughnessy
209
N
F3C Cy3P
Mo Cl
F3C O
H3C O Ru Ph
F3C CMe2Ph Cl
F3C CH PCy3 Ph
3
Schrock Grubbs
The Schrock metathesis catalyst
Synthesis:
CH3 Cl CH3 OTf

RH2C NAr 3 HOTf
O NAr 2 RCH2MgCl O NAr
Mo Mo Mo
O NAr RH2C dme O CHR
Cl NAr
CH3 CH3 OTf
F3C NAr
F3C OH F3C
H3C Mo
F3C O
H3C O
F3C R
F3C CH
3
The molybdenum carbene is very sensitive to oxygen and moisture as well as protic compounds
(alcohols, ketones, aldehydes, etc.), but is stable for long periods in an inert atmosphere.
Reactivity and mechanism:
The Schrock metathesis catalysts carry out the living ring opening metathesis polymerization of cyclic
olefins.
LnMo=CHR MoLn PhCHO

R R Ph
n n
-LnMoO F3C CF3
F3C CF3 F3C CF3
Electron withdrawing alkoxide groups give higher reaction rates in metathesis reactions. The t-BuO
complex forms stable metallacycles that only slowly decompose to give the ring opened product.
Kevin Shaughnessy
210
F3C CF3
NAr
F3C CF3 ArN H
Mo Mo
t-Bu O
O t-BuO t-Bu
t-Bu Ot-Bu
t-Bu
NAr
NAr H t-Bu
t-BuO slow Mo
Mo t-Bu O
t-BuO ∆G‡ = 24 kcal/mol O
t-Bu F3C CF3 t-Bu
CF3
F3C
The increased reactivity towards coordinating ligands of the –O(CF3)2CH3 complexes is seen in the
reaction with PMe3. This complex forms a stable adduct, while the t-BuO- complex does not.
(Organometallics, 1991, 10, 1832-1843)
NAr
F3C PMe3 PMe3
PMe3 ArN H ArN
Mo t-Bu
F3C O Mo Mo
H3C O RO t-Bu RO H
F3C t-Bu OR OR
F3C CH
3 anti-adduct syn adduct
The alkylidene can exist in two rotameric forms, but in solution only the syn rotomer is observed by NMR.
The rate of interconversion between these forms is dependent upon the alkoxide ligand. The t-BuO-
complex interconverts 108 times faster than the –O(CF3)2CH3 complex. The anti form reacts faster with
alkenes to give ROMP.
NAr NAr
ka/s
Mo H Mo t-Bu
RO RO
RO ks/a RO
t-Bu H
anti syn
Asymmetric Ring Closing Metathesis
Schrock in collaboration with Hoveyda have applied the molybdenum alkylidenes to asymmetric synthesis
(Chem. Eur. J., 2001, 7, 945-950). By replacing the alkoxide ligands with chiral diols, enantioselective
RCM reactions are possible. This methodology can be applied to the resolution of racemic dienes or
enantioselective ring closing of meso-dienes.
Kevin Shaughnessy
211
NAr
Ph
t-Bu Mo
O CH3
O CH3
t-Bu
OSiEt3 5% OSiEt3
OSiEt3
H3C H3C
H3C C6H6, r.t. H3C

krel > 25
ArN
t-Bu Mo
O
O R
t-Bu
O
O
H3C CH3 cat (2 %) CH3
99 % ee, 93 %
neat, 5 min, r.t. H3C H
H3C CH3 CH3
Advantages of the Schrock catalyst:

• Very high activity
• Allows synthesis of tri- and tetra-substituted alkenes
• Efficient asymmetric ring closing metathesis.
Disadvantages of the Schrock catalyst:
• Requires rigorous exclusion of air and moisture
• Limited functional group tolerance
The Grubbs Metathesis Catalyst
The Schrock catalyst and related complexes based on electrophilic metal centers suffered from limited
tolerance of functional groups. While the Schrock catalyst would tolerate ketones, esters, and amides,
function groups such as aldehydes, alcohols, and acids were not tolerated, nor was water. It would be
expected that lower-valent , late transition metal complexes would be more tolerant of electrophilic and
protic functional groups. This is because the carbene would be less nucleophilic (more Fischer
character).
Grubbs has developed an excellent family of catalysts based on Ru alkylidienes (Acc. Chem. Res. 2001,
34, 18-29).
Kevin Shaughnessy
212
Synthesis:
The synthesis of the first generation catalyst occurs in high yield and has been carried out in 10 kg
batches.
Cl
Cy3P
PCy3, Et3N H Ph Cl
H2, sec-BuOH Ph Ru Ph
[RuCl2(COD)]x RuH(H2)Cl(PCy3)2
80 ˚C 0˚C Cl
PCy3 Ph
95 %
Reactivity and Mechanism:
The Grubbs catalyst carries out living ROMP polymerization similar to the Schrock catalyst, but with lower
activity. The Grubbs catalyst shows improved functional group compatibility, though. In fact, aqueous
phase ROMP polymerizations are possible with water-soluble versions of the Grubbs catalyst.
The Grubbs catalyst has been most widely used in organic synthesis for RCM and CM reactions, due to
it’s stability and good functional group compatibility.
RCM (J. Am. Chem. Soc., 1997, 119, 2733)
N N
S S
H H
O O
OH Grubbs OH
81 %
CH3 CH3 9:1 E:Z
CH3 CH3
O O
OH OH
desoxyepothilone A
Heterocross Metathesis (J. Am. Chem. Soc., 2000, 122, 58-71
Grubbs OAc
OAc
OAc
80 %
3:1 E/Z
Two main pathways have been suggested for the metathesis propagation step. There are several pieces
of data suggesting that phosphine dissociation is required for metalacycle formation. (J. Am. Chem. Soc.,
1997, 119, 3887)
• Inverse rate dependence on [PCy3]

• Observation of a monophosphine olefin complex in the reaction (J. Am. Chem. Soc, 1997, 119,
7157)
• Observation of chelated metalacyclobutane species.
• Quantum chemical calculations.
Kevin Shaughnessy
213
Cy3P
Cl R Cy3P
Cl
Cl Ru
Cl Ru A
R
R
R
Cy3P Cy3P Cy3P
Cl R Cl R Cl
R minor
Ru Cl Ru Cl Ru
Cl R
PCy3 PCy3 R PCy3
R
Cy3P Cy3P
Cl R Cl
Ru Ru B
Cl R Cl R
R
While the dissociation was well established early on, there is a great deal of debate about the nature of
the metallacyclobutane intermediate. Two likely structures are A and B. Recently Piers was able to
generate and observe the metallacyclobutane and showed that it is in fact the symmetric structure B.
(JACS, 2005, 127, 5032).
Mes N N Mes
Mes N N Mes
Cl Cl
Ru + Cy3PCHCH2 B(C6F5)4
Ru
Cl -50 °C
PCy3 Cl
B(C6F5)4
The activity of the Grubbs system is dependent on both the phosphine and the halide ligands.
Larger more electron donating phosphines give higher rates
Smaller less electron donating halides give higher rates.
R3P
L
Ru
L CPh2
PR3
+ H2C=CH2
EtO2C CO2Et EtO2C CO2Et

Cl > Br > I
PCy3 > Pi-Pr3 > PhPCy2 > PhPi-Pr2
Design of the next generation of Grubbs catalysts
The mechanistic results suggested that the active species was a monophosphine ruthenium alkylidene.
Therefore, stable monophosphine complexes were sought. The ideal catalyst would have high activity
Kevin Shaughnessy
214
and stability. This requires easy formation of the 14 electron monophosphine complex without
decomposition.
• A chelated complex was stable at high temperatures, but had low activity
• Replacement of a phosphine with a weakly coordinating ligand, gave a very active catalyst with a
short lifetime.
• N-Heterocyclic carbenes are stronger s-donors than phosphines, but also have stronger M-L
bonds.
o The bis carbene complex had low activity because carbene dissociation is slow.
o The mixed carbene/phosphine complex is both highly active and very stable.
Cy3P Cy3P
Cl R Cl
Ru Ru Need system that favors
Ph Ph formation of alkene complex,
Cl Cl but is stable.
PCy3 PCy3
R
Ar Cy N N Cy
N Mes N N Mes
Cl
Cl N Cl
Cl Ru
Ru
Ph Ru Ph Ru
O Cl
Ph Cl Ph
PCy3 Cl Cy N N Cy PCy3
PCy3
Stable, but low activity High activity, but unstable Low activity High actvity and Stability
Mes N N Mes
Cl Grubbs-Hoveyda Catalyst
High activity
Ru Potentially recyclable
Cl Slower initiation than Grubbs 2
O
i-Pr
The monocarbene complex and the saturated carbene analog allow reactions that were previously only
possible with the Schrock catalyst.
Kevin Shaughnessy
215
Mes N N Mes
Cl
Ru
Ph E E
Cl
E E PCy3
+ H2C CH2
cat CHO
AcO AcO
8 CHO 8
O O
NO2 NO2
O
R R
N CO2Me cat N CO2Me
N N
O O toluene O O
O O
O O
Mes N N Mes
Cl
HCV-N3: Protease Inhibitor
cat = Ru Boehringer-Ingelheim
Cl R = H: 82% (0.01 M)
O NO2 R = Boc: 93% (0.2 M)
i-Pr
The second generation of Grubbs catalysts combine the high activity of the Schrock catalysts with good
stability and functional group tolerance. The only application where the Schrock catalyst is still superior is
in the asymmetric RCM reactions.
Stereoselectivity in Olefin Metathesis
Alkene metathesis is typically an equilibrium process that is under thermodynamic control. For cross-
metathesis to form acyclic alkenes, the E-isomer is generally favored, but a mixture of E and Z is usually
formed. In RCM reactions, there is generally a preference for the Z-isomer, unless the ring is large
enough to accommodate a trans-alkene. Significant efforts have been made to develop stereoselective
catalysts for CM.
Stereoselectivity in CM depends on the orientation of the alkylidene substituent and the substituents on
the coordinated alkene as the metallacyclobutane is formed. The preferred structure would place the
substituents trans, leading to an E alkene.
Kevin Shaughnessy
216
M=CR2
R2
R1 R2 R1 R1
R2
major minor
Cy3P L L Cy3P
Cl Cl Cl Cl
2
Cl Ru R Cl Ru 2 Cl Ru Cl Ru
R1 R R1 R1 R1
R2 R2
L L
Cl Cl
+ R2 +
Ru CH2 R1 R1 Ru CH2
R2 Cl
Cl
Z-selective CM:
The Z-alkene is generally thermodynamically less stable, so it usually the minor product. A number of
research groups have worked to develop Z-selective catalyst systems. Grubbs, Hoveyda, and Schrock
have all developed systems with high Z-selectivity. The proposed mechanism for stereocontrol is that a
large ligand favors placing the alkene substituents away from this ligand, resulting in them being syn in
the metallacyclobutane. This results in a Z-alkene. The alternative results in a steric clash with the
ligand.
N N Mes Mes N N Mes

1 Cl S 2
iPr iPr
O Ru Ru
N OO N
O S O
iPr iPr N Mo Ph
Cl O
Grubbs, JACS, 2012, 693 Hoveyda, Nature, 2015, 517, 181 Br
Br
Ph TBSO
1
89%
Ph Ph 95% Z
C6H13 Schrock, Hoveyda, Nature, 2011,

HO [Ru]
1: 53%, 93:7 Z:E 471, 461
2: 66%, 95:5 Z:E
C6H13
Ph
N N N N
L L
Ru Ru R
L L
R R R
Kevin Shaughnessy
217
E-Selective CM
Although E-alkenes are generally favored, there are no catalyst systems that give a high preference for E-
alkenes. Grubbs has developed a system that is capable of stereospecific cross-metathesis of internal
alkenes. Using this catalyst, Z-alkene starting materials are exclusively converted to Z-alkene products.
Similarly, E-alkenes are converted to E-alkene products. E-Alkenes are poor substrates, however and
generally give slow reactions and low yields. Grubbs found that using smaller fluorine substituents and
the N-aryl groups gave a catalyst with low E/Z selectivity for terminal alkenes. As a result, the starting
alkene geometry determines the product stereochemistry. A similar mechanism is proposed with the
large substituents on the NHC ring exerting control over the alkylidene and coordinated alkene. With Z-
alkenes, all substituents want to be away from the NHC ligand. In the case of E-alkenes, the alkene will
coordinate with one R group pointing into the open space in front of the NHC ring. This leads to an E-
product.
F F
N N
FS F
Cl Ru
S O
iPr Ph
Cl 6 mol % 52%
7 7 7 >99:1 E:Z
7 2
7 2
70%
7 7 7 <1:99 E:Z
N N N N N N N N
S S R2 S S
R2 R2
Ru Ru
Ru RRu
2
R2 R1
R1 R2 S R1 S R1 S
R2 S R2
Favored Disfavored
N N N N N N N N
S S R2 S S
R2 R2Ru R2
Ru Ru Ru
R2 R1 R1 R1 R1
S R2 S S S
R2 R2
Favored Disfavored
Alkyne Metathesis
Although alkene methathesis is well established as a synthetic methodology, particularly with the Grubbs
catalysts, the analogous alkyne metathesis is much less well developed.
Kevin Shaughnessy
218
LnM R
R1 R2 R3 R4 R1 R3 R2 R4
R2 R3 R2 R4 R2 R4
R2 R4
MLn
MLn MLn R1 MLn
R1 R1 R1
Fürstner (JACS, 2000, 122, 11799 and references therein, Angew. Chem. Int. Ed. 2013, 52, 2794,
review) was one of the first to adopt alkyne metathesis for organic synthesis. He showed that a Mo(III)
tris(amide) could be used as a catalyst precursor for the diyne ring closing metathesis as part of the
synthesis of prostaglandins.
t-Bu
t-Bu
N
N Mo t-Bu
N
O
O
O
O
TBSO H11C5 O CH2Cl2
TBSO H11C5 O
The active catalyst was formed from the reaction of the Mo precursor and the reaction solvent (CH2Cl2) to
give a mixture of chloride complex and alkylidyne. Moore (JACS 2004, 126, 329-335) showed that the
alkylidyne could be made in high yield by recycling the Mo-Cl complex. Mg was used to reduce the
chloride complex back to the starting Mo-amide complex. In this way nearly all of the Mo would
eventually be converted to the desired alkylidyne.
H
Cl
t-Bu t-Bu t-Bu
t-Bu t-Bu t-Bu
N CH2Cl2 N N
N Mo N Mo N Mo t-Bu
t-Bu t-Bu
Ar N Ar Ar N Ar Ar N Ar
Ar Ar Ar
Mg
Kevin Shaughnessy

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Organometallic Chemistry of the Transition Metals: Mechanisms

and Applications to Catalysis

Department of Chemistry & Biochemistry

The University of Alabama, Tuscaloosa, AL

Updated fall 2019

Updated versions of these notes can be found at: http://kshaughnessy.people.ua.edu/resources.html

1. Structure and Bonding .............................................................................................................................. 3

1. Structure and Bonding

Basic Picture of Metal-Ligand Bonds

Types of Ligand Coordination

Three generic classes of ligands:

AuII Cl Au(II) rare oxidation state

L L AuI Cl Au(I) common

Types of ligand coordination:

Terminal: Ligand is bound to only one metal center (L-M or X-M)

The 18-Electron Rule

Ionic Model: # e = # metal electrons (dn) + # ligand electrons

Covalent Model H Ionic Model

Covalent Model Ionic Model

Covalent Model O Ionic Model

Ligand Name Covalent Model lonic Model

Nitrosyl (linear, NO+), terminal or bridging) 3 +1 2

Carbene (CYR, where Y = substituent with π

CO, CNR (bridging or terminal) 2 0 2

PR3, AsR3, SbR3, NR3, imines, nitriles, ethers,

Terminal dinitrogren (N2) 2 0 2

Terminal or bridging Alkyl (-CR3) 1 -1 2

h1-Aryl, alkenyl, or alkynyl 1 -1 2

ER3 or EX3 (E = Si, Ge, Sn) 1 -1 2

Alkoxide (-OR), thiolate (-SR), amide (-NR2), or

Halide (F-, Cl-, Br-, I-) or pseudohalide (-CN, -OTs, etc) 1 -1 2

Bridging alkoxide, thiolate, amide, or phosphide 3 -1 4

Bridging Halide (µ-X)

h2-Alkenyl (terminal or bridging)

Carbene (CR2 where R = substituent with no π

Alkylidine or carbyne, terminal M C R 3 -3 6

Application of the 18-electron rule:

V(CO)6 Cr(CO)6 (CO)5Mn-Mn(CO5 Fe(CO)5 (CO)3Co(µ-CO)2Co(CO)3 Ni(CO)4

Common exceptions to the 18 electron rule:

Me Pd Me Me3P Rh Cl Me3P Au CH3

Formal Oxidation State and d electron configuration

Consider the range of possible formal charges on metal centers:

Coordination Geometry Preferred dn Example

Crystal Field Theory

t2g dxy dxz dyz

eg orbitals (ds) can form s bonds with the ligands

Crystal field splitting of other common geometries:

dxy, dyz, dxz dx2-y2

dx2-y2 and dz2 dyz and dxz

High spin and Low spin complexes

– 2nd and 3rd row transition metals tend to have higher D

– Higher oxidation state metals have higher D

Ligand Field Theory

Other π-acceptor ligands: NO, N2, CN-R, PF3

2: Survey of Ligand Types--Part 1 (L-type ligands)

A. Neutral s-donor/π acceptors: CO, phosphines, and carbenes

s-Donor: The HOMO of CO is a non-bonding lone pair on the C. CO is a strong s-donor.

The degree of back bonding can readily be determined by IR spectroscopy.

V(CO)6 Cr(CO)6 Mn2(CO)10 Fe(CO)5 Co2(CO)8 Ni(CO)4

[Ti(CO)6]2- [V(CO)6]- Cr(CO)6 [Mn(CO)6]+ [Fe(CO)6]2+ CO

Pd PR3 σ* P π acceptor MO M-P backbonding interaction

The steric parameter--q--The Cone Angle:

Steric parameters for palladium complexes of different ligands