Organometallic Reactions I:

Reactions That Occur at the Metal

Ligand Substitution
Oxidative Addition
Reductive Elimination
 Actors and spectators

Actor ligands are those that dissociate or undergo a chemical

transformation
(where the chemistry takes place!)

Spectator ligands remain unchanged during chemical

transformations
They provide solubility, stability, electronic and steric influence
(where ligand design is !)
Ligand Substitution
 Ligand substitution reactions:
overview
 Studied systematically for the reactions of
phosphines with metal carbonyls (Basolo)
 Classification
 D Dissociative (comparable to the SN1 limiting case)
 A Associative (comparable to the SN2 limiting case)
 I Interchange / Intermediate
• Ia (comparable to typical SN2 reactions)
• Id (comparable to typical SN1 reactions)
 Notes:
 "Labile" and "Inert" are kinetic terms
 "Stable" and "Unstable" are thermodynamic terms
Ligand Substitution Reactions
 Substitution reactions can be:
Associative (SN2)
Dissociative (SN1)

 They can involve

2e-ligands: CO, PR3 C2H4, …
one electron ligands.
 Ligand Substitution Reactions
The following trends have been observed

1. M-L bonds from two-electron donors such

as CO are at most half as strong as the
familiar C-H and C-C bonds in organic
chemistry, thus dissociative mechanisms
are possible.
2. Polyhapto ligands such as η6-
cyclopentadienyl and η6-arene have
much stronger M-L bonds than CO and
will not undergo dissociative substitution
 Ligand Substitution Reactions

3. M-L bond strengths in general increases

down a triad as third row> second row >
first row.
Note that there are many exceptions.

4. The general order of bond strengths has

been established:
Cp > MexC6H6-x > C6H6 > CO ~ PMe3 ~
Olefin > PPh3 >Py > CH3CN >THF ,
acetone, ethanol
 Dissociative Mechanism
Only bond breaking is involved in the formation of an intermediate of
decreased coordination number.
Typical of 18e- complexes
 Dissociative displacements

 Observed for 18e carbonyls

 Rates: d8 > Td d10 > Oh d6
 Y-intermediate is favored by L
being a good π-donor; T-
intermediate is favored by a
high trans-effect L.
 Rates for TM: 3rd row < 2nd
row > 1st row
 Dissociation is accelerated
for bulky ligands.
 Weakly bound solvent
molecules are often useful
ligands synthetically.
 Associative substitutions

 Often adopted by 16e complexes:

 Found for 18e complexes that have a ligand which can rearrange
(slip):
 Associative Mechanism
Bond making is involved in the formation
of an intermediate or transition state of
increased coordination number.
 Associative Mechanism
Bond making is involved in the formation
of an intermediate or transition state of
increased coordination number.

Fast

Associative mechanisms are typical of 16e- complexe

 Associative Mechanism
Associative substitution reactions
involving coordinatively unsaturated 16-
electron systems are relatively fast
(rates ~ 104 sec).
 Rearrangements of coordinatively
unsaturated species
 When a ligand dissociates, one of the remaining ligands rearranges to
fill the vacant site created: the reverse of the slippage process.
 Analogous to neighboring group participation in organic chemistry
 Synthesis: nucleophilic attack on
the metal

 Very useful and rather general method

 Common reagents are RLi, RMgX (or R2Mg), ZnR2, AlR3, BR3, and
PbR4.
15
 Ligand Substitution
Reactivity of Coordinated Ligands
 Why care about substitution ?
Basic premise about metal-catalyzed reactions:
 Reactions happen in the coordination sphere of the metal
 Reactants (substrates) come in, react, and leave again
 Binding or dissociation of a ligand is often the slow, rate-
determining step

This premise is not always correct, but it applies in the vast majority
of cases.
Notable exceptions:
 Electron-transfer reactions
 Activation of a single substrate for external attack
 peroxy-acids for olefin epoxidation
 CO and olefins for nucleophilic attack
Dissociative ligand substitution
Example:

Factors influencing ease of dissociation:

 1st row < 2nd row > 3rd row
 d8-ML5 > d10-ML4 > d6-ML6
 stable ligands (CO, olefins, Cl-) dissociate
easily (as opposed to e.g. CH3, Cp).
 Dissociative substitution in ML6

16-e ML5 complexes are usually fluxional;

the reaction proceeds with partial inversion, partial
retention of stereochemistry.

The 5-coordinate intermediates are normally too reactive to be

observed unless one uses matrix isolation techniques.
 Associative ligand substitution

Example:

Sometimes the solvent is involved.

Reactivity of cis-platin:
 Ligand Rearrangement
Several ligands can switch between n-e and (n-2)-e situations,
thus enabling associative reactions of an apparently
saturated complex:
Redox-induced ligand substitution
Unlike 18-e complexes, 17-e and 19-e complexes are labile.
Oxidation and reduction can induce rapid ligand substitution.

 Reduction promotes dissociative substitution.

 Oxidation promotes associative substitution.
 In favourable cases, the product oxidizes/reduces the
starting material ⇒ redox catalysis.
Redox-induced ligand substitution

Initiation by added reductant.

Sometimes, radical abstraction produces a 17-e species

Photochemical ligand substitution
Visible light can excite an electron from an M-L bonding orbital
to an M-L antibonding orbital (Ligand Field transition, LF).
This often results in fast ligand dissociation.

Requirement: the complex must absorb, so it must have a

color! or use UV if the complex absorbs there
Photochemical ligand substitution
Some ligands have a low-lying π* orbital and undergo Metal-to-
Ligand Charge Transfer (MLCT) excitation.
This leads to easy associative substitution.
 The excited state is formally (n-1)-e !
 Similar to oxidation-induced substitution

HOMO LUMO

M-M bonds dissociate easily (homolysis) on irradiation

⇒ (n-1)-e associative substitution
Electrophilic and nucleophilic attack
on activated ligands
Electron-rich metal fragment:
ligands activated for electrophilic attack.

H2O is acidic enough to protonate this coordinated ethene.

Without the metal, protonating ethene requires H2SO4 or similar.
Electrophilic and nucleophilic attack
on activated ligands
Electron-poor metal fragment:
ligands activated for nucleophilic attack.

BuLi does not add to free benzene, it would at best metallate it

(and even that is hard to do).
 Electrophilic attack on ligand
Hapticity may increase or decrease.
Formal oxidation state of metal may increase.
 Electrophilic Addition

 Is formally oxidation of Fe(0) to FeII (the ligand becomes anionic).

 Ligand hapticity increases to compensate for loss of electron.
 Electrophilic abstraction
Electrophilic abstraction
also by Ph3C+, H+

Alkyl exchange also starts with electrophilic attack:

 Electrophilic attack at the metal
If the metal has lone pairs, it may compete with the ligand for
electrophilic attack
Transfer of the electrophile to the ligand may then still occur
in a separate subsequent step
 Electrophilic attack at the metal
Can be the start of oxidative addition

(although this could also happen via concerted addition)

Key reaction in the Monsanto acetic acid process:

One reaction, multiple mechanisms
Concerted addition, mostly with non-polar X-Y bonds
 H2, silanes, alkanes, O2, ...
 Arene C-H bonds more reactive than alkane C-H bonds (!)

Intermediate A is a σ-complex.
Reaction may stop here if metal-centered lone pairs are not
readily available.
Final product expected to have cis X,Y groups.
One reaction, many applications
 Oxidative addition is a key step in many transition-metal
catalyzed reactions
 Main exception: olefin polymerization
 The easy of addition (or elimination) can be tuned by the
electronic and steric properties of the ancillary ligands
 The most common applications involve:

a) Late transition metals (platinum metals)

b) C-X, H-H or Si-H bonds

Many are not too sensitive to O2 and H2O and are now
routinely used in organic synthesis.

Oxdative addition,
reductive elimination
 The Heck reaction

 Pd often added in the form of Pd2(dba)3. dba, not quite an

innocent ligand

 Usually with phosphine ligands.

 Typical catalyst loading: 1-5%. But there are examples with
turnovers of 106 or more
 Heterogenous Pd precursors can also be used, but the
reaction itself happens in solution
 The Heck reaction
 For most systems,
we don't know the
coordination environment
of Pd during catalysis.

 At best, we can detect

one or more resting states.

 The dramatic effects of

ligand variation show
that at least one ligand
is bound to Pd for
at least part of the cycle.
 The Heck reaction

 Works well with aryl iodides, bromides

 Slow with chlorides
 Hardly any activity with acetates etc.
 Challenges for "green chemistry"

 Pt is ineffective
 Probably gets "stuck" somewhere in the cycle
 Suzuki and Stille coupling

 Glorified Wurtz coupling

 Many variations, mainly in the choice of electrophile

 Instead of B(OH)2 or SnMe3, also MgCl, ZnBr, etc

 The Suzuki and Stille variations use convenient, air-stable

starting materials
 Suzuki and Stille coupling
 The oxidative addition and
reductive elimination steps
have been studied extensively.

 Much less is known about

the mechanism of
the substitution step.
 The literature mentions
"open" (3-center) and
"closed" (4-center) mechanisms

 This may well be different

for different electrophiles.
 Association-Dissociation of Lewis acids

Lewis acids are electron acceptors, e.g. BF3, AlX3, ZnX2

H H
W: + BF3 W BF3
H H

This shows that a metal complex may act as a Lewis base

The resulting bonds are weak and these complexes are called adducts
 Association-Dissociation of Lewis bases

A Lewis base is a neutral, 2e ligand “L” (CO, PR3, H2O, NH3,

C2H4,…)
in this case the metal is the Lewis acid

HCo(CO)4 HCo(CO)3 + CO

For 18-e complexes, dissociative mechanisms only

For <18-e complexes dissociative and associative mechanisms are possible
 Nucleophilic displacement (SN2)

 Methyl, allyl, acyl, and benzyl halides

 The ligands have a strong effect on the nucleophilicity of the

metal center.
 Reactivity of R-X:
• X: I > Br > Cl
• R: Me > Et > iPr > tBu
 If chiral RX are used then inversion of configuration is
observed:
 Sigma-bond metathesis

 It avoids the TD barriers

of the C-H activation /
substitution step.
 It is found for early TM
with d0 configuration.
 Why position β cannot be C
The reaction is best described as a nucleophilic substitution of H at either C or Si in the
coordination sphere of Ln.
The transition state is a pentacoordinated
anionic CH5- or SiH5- which is energetically
highly unfavorable for C and much more
favorable for Si.

The energy barrier for C at the β position is lowered

with electronegative substituents (F), known to
stabilize a hypervalent species, but not vinyl or phenyl.
 Electrophilic activation
Pd2+, Pt2+ and/or Pt4+, Hg2+, Tl3+.

Shilov, 1972

Alkane activation step

σ bond metathesis with high-valent, late
TMs
 Midterm 2005: Recently, Hartwig et al. (J. Am. Chem. Soc. 2005, 127,
14263-14278) published mechanistic studies on the functionalization of arenes
by diboron reagents catalyzed by iridium complexes:

For each step shown in the catalytic cycle

indicate the mechanism (type of reaction).
Where you can envision more than one
possibility, write down all of them (at
least two) discussing arguments that
support your proposal or that are
against it (at least one of each). If you
consider that some intermediates
are not shown, draw those intermediates.
Indicate formal oxidation state and
electron count for each iridium complex.
Endo methyl migration: aromatic stablization energy
Jim D. Atwood, Michael J. Wovkulich and David C.
Sonnenberger, Acc. Chem. Res. 1983, 16, 350-355
 Role of Ligand Substitution in Ferrocytochrome c Folding
Jason R. Telford, F. Akif Tezcan, Harry B. Gray, and Jay R. Winkler
Biochemistry, 1999, 38, 1944-1949
Factors Influencing the Reactivity of Transition-Metal Complexes

Effective Atomic Number (EAN)

① Diamagnetic organometallic complexes of transition metals

may exist in significant concentration at moderate temperature
only if the metal valence shell contains 16 or 18 electrons.

② Organometallic reactions, including catalytic ones, proceed by

elementary steps involving only species with 16 or 18
electrons.
Coordination Number and Geometry
A simple d orbital only σ bonding angular overlap analysis of structural
preference energies for ML6, ML5, and ML4 geometries shows that for
a d6 atom, the ML6 geometry is strongly favored relative to either ML5
or ML4. For a d8 atom, the ML5 trigonal bipyramid is favored relative to
ML6 or tetrahedral ML4, but a square-planar geometry is equally
preferred (hence the large number of 16-electron square-planar d8
complexes). For a d10 atom, there is no distinction in angular overlap
terms between square-planar and tetrahedral ML4 geometries although
the latter will be preferred in terms of minimization of ligand-ligand
repulsions.
James A. S. Howell & Philip M. Burkinshaw, Chem. Rev. 1983, 83, 557-599
 Volume changes accompanying ligand substitution reactions
assuming a negligible change in volume of the first coordination
sphere of the complex
trans directing effect rationalized within the general accepted
associative process on square-planar complexes
Cl- promoted inversion of square-pyramidal [FeCl(porphyrin)] complexes
David T. Richens, Chem. Rev. 2005, 105, 1961-2002
Shunsuke Sato, Yuji Ohashi, Osamu Ishitani, Ana Maria Blanco-
Rodrıguez, Antonın Vlcek, Jr., Taiju Unno, and Kazuhide Koike,
Inorg. Chem. 2007, 46, 3531-3540
“Inverse-Electron-Demand” Ligand Substitution in Palladium(0)-Olefin Complexes
Shannon S. Stahl, Joseph L. Thorman, Namal de Silva, Ilia A. Guzei, and Robert
W. Clark, J. AM. CHEM. SOC. 2003, 125, 12-13
J. Phys. Chem. 1996, 100, 18363-18370
Organometallics, 1986, 5, 1703-1706