Ligand SubstitutionReactivity of Coordinated Ligands

Peter H.M. Budzelaar

H2O PdCl

Cl

H2O PdH

ClOH

H2O PdH

Cl O

Cl Pd ClCl

Cl 2--

Cl PdCl

Cl

H2O PdCl

OH

H2O PdCl

OH"β-H elim"

- 2 e (CuCl2 → CuCl)

C2H4 H2O

H2O PdCl

ClOH

-

ins

Cl-CH3CHO

H2O Pd ClH

Cl -

Pd(0) + H+ +H2O + 2 Cl-

OH-

- Cl-

β-H elim

Ligand Substitution2

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 appliesin 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

Ligand Substitution3

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).

LnM CO LnM LnM L'+ CO L'

18 e 16 e 18 e

Ligand Substitution4

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.

18-e

oct

16-e

SP distortedTBP

or

Ligand Substitution5

Associative ligand substitution

Example:

Sometimes the solvent is involved.Reactivity of cis-platin:

16 e 18 e

L'Ln-1M L'LnM LnM L'

- L

16 e

(NH3)2PtCl2 (NH3)2Pt(Cl)(Br)

(NH3)2Pt(Cl)(H2O)+

Br-

- Cl-

H2O - Cl- Br-- H2O

NucleoBase - H2O

(NH3)2Pt(Cl)(NB)+

slow

fast

fast- Cl- slow

Ligand Substitution6

Ligand rearrangement

Several ligands can switch between n-e and (n-2)-e situations,thus enabling associative reactionsof an apparently saturated complex:

M NO

M N O

3-e 1-e

M M3-e5-eM

CO

RM

O

R

(1+2)-e 1-e

Ligand Substitution7

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.

L'

LnM

LnM+ LnM L' +

LnM- Ln-1M- + L

- e-

+ e-18-e

17-e 19-e

19-e 17-e

Ligand Substitution8

Redox-induced ligand substitution

CO

L

Fe(CO)4L

Fe(CO)4L

Fe(CO)4

Fe(CO)5

Fe(CO)5

Initiation by added reductant.

Sometimes, radical abstractionproduces a 17-e species(see C103).

Ligand Substitution9

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 colour!or use UV if the complex absorbs there

dπ

dσhν

M(CO)6

Ligand Substitution10

Photochemical ligand substitution

Some ligands have a low-lying π* orbital and undergoMetal-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

M-M bonds dissociate easily (homolysis) on irradiation⇒ (n-1)-e associative substitution

dπ

dσhν

M(CO)4(bipy)

π*

HOMO LUMO

Ligand Substitution11

Electrophilic and nucleophilic attackon 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.

NN

NRh S

N

++

SH+N

N

NRh

N

+

Ligand Substitution12

Electrophilic and nucleophilic attackon activated ligands

Electron-poor metal fragment:ligands activated for nucleophilic attack.

-

CrOCOC

CO

Bu

HLi+

CrOCOC

CO

BuLi

BuLi does not add to free benzene, it would at best metallate it(and even that is hard to do).

Ligand Substitution13

Electrophilic attack on ligand

Hapticity may increase or decrease.Formal oxidation state of metal may increase.

H+MI

+

MI

H+M(0) MII

+

Ligand Substitution14

Electrophilic addition

• Is formally oxidation of Fe(0) to FeII (the ligand becomes anionic).• Ligand hapticity increases to compensate for loss of electron.

O

Fe(CO)3

OEt+

Fe(CO)3

Et3O+

Ligand Substitution15

Electrophilic abstraction

Electrophilic abstractionalso by Ph3C+, H+

Alkyl exchange also starts with electrophilic attack:

Cp2ZrMe

Me

B(C6F5)3 Cp2ZrMe

+

MeB(C6F5)3-

16 e 14 e

+

Zn

Me

MeZnMe

Me

MeZn

Me

MeZn

Me

Ligand Substitution16

Electrophilic attack at the metal

If the metal has lone pairs, it may compete with the ligandfor electrophilic attack

Transfer of the electrophile to the ligand may then still occurin a separate subsequent step

Fe

+

Fe H

Ni

H+

H+Ni

+?via?

Ligand Substitution17

Electrophilic attack at the metal

Can be the start of oxidative addition

(although this could also happenvia concerted addition)

Key reaction in theMonsanto acetic acid process:

I2(CO)2Rh Me I I2(CO)2RhMe + I- I3(CO)2RhMe

MeOH + CO MeCOOHHI"Rh"

H2O

HI CH3OH

CH3I

CH3COOH

CH3COI

Rh(CO)2I2-

MeRh(CO)2I3-

MeCORh(CO)I3-

MeCORh(CO)2I3-

CO

Ligand Substitution18

Nucleophilic attack on ligand

Nucleophile "substitutes" metal⇒ hapticity usually decreases

Oxidation state mostly unchanged

Competition: nucleophilic attack on metalusually leads to ligand substitution

Ligand Substitution19

Nucleophilic abstraction

Mostly ligand deprotonation

NaHCr

OCOC

CO

Na+

-

CrOCOC

CO

Cp2WH2BuLi

Cp2WH Li

Ligand Substitution20

Nucleophilic addition

Key reaction of the Wacker process:

(H2O)Cl2Pd + OH- (H2O)Cl2Pd

OH-

C2H4 + ½ O2PdCl2, H2O

CH3CHOCuCl2

Ligand Substitution21

The Wacker process

H2O PdCl

Cl

H2O PdH

ClOH

H2O PdH

Cl O

Cl Pd ClCl

Cl 2--

Cl PdCl

Cl

H2O PdCl

OH

H2O PdCl

OH"β-H elim"

- 2 e (CuCl2 → CuCl)

C2H4 H2O

H2O PdCl

ClOH

-

ins

Cl-CH3CHO

H2O Pd ClH

Cl -

Pd(0) + H+ +H2O + 2 Cl-

OH-

- Cl-

β-H elim

Ligand Substitution22

The Wacker process

Characteristics of the Wacker process:• The oxygen in the product derives from water,

not directly from the oxygen used as oxidant• higher olefins yield ketones, not aldehydes• large amounts of halides required: corrosive• side products resulting from nucleophilic attack

of halide on olefin

No longer important for acetic acid synthesisSeveral variations (with more complicated nucleophiles)

used in organic synthesis

Ligand Substitution23

Nucleophilic attack on the ligand

How can you distinguish between internal and externalattack of OH- ?

H2O PdCl

Cl

H2O PdOH

Cl-

OH-H2O Pd

Cl

Cl OH-

-H2O Pd

O

Cl

H

ins

OH- - Cl-??

H2O PdCl

Cl OH-

PdCO

OH

O

O

CO- Cl-

Pd

O

HOins

nuclattack

Use trans-CHD=CHD and trap the intermediatePd-C-C-OH with CO:

Ligand Substitution24

Using isotopic labellingto study mechanisms

OH-

O

OD

DPd

HO

D

D

Pd

HO

D

D

PdD

D

O

OD

DPd

D

HOD

PdOH

D

D

CO

CO

Ligand Substitution25

Using isotopic labellingto study mechanisms

Perform reaction in D2O:

Could acetaldehyde be formed directly as vinyl alcohol ?

dissOPd

H

ins

CH3

OHPd

OH

H2O

CH3

OHdiss

OHOHPd

H

"β-H elim"

dissOPd

D

ins

CH3

OHPd

OD

D2O

CH2D

OHdiss

ODODPd

H

"β-H elim"