HYDROGENATION

Concerned with two forms of hydrogenation: heterogeneous (catalyst insoluble) and

homogeneous (catalyst soluble)

Heterogeneous Catalysis
Catalyst insoluble in reaction medium
Reactions take place on catalyst surface
Rate of reaction and selectivity dependant on active sites on surface
Active sites are the part of the catalyst substrate and hydrogen can adsorb on
By blocking or poisoning active sites the reactivity of a catalyst is reduced and
the selectivity increased
Good poisons are metal cations, halides, sulfides, amines and phosphines
Reaction is a surface phenomenon and not fully understood
H2 disassociation / activation
catalyst surface

H*
H*

adsorption of H2

predominantly syn
hydrogenation
*H
H

alkene adsorption

alkene activation

H*

*H

H*

H*

Differences in catalyst arise due to ability of each metal to bind to various substrates and the
different modes of binding
Order of Reactivity of Various Metals
Pt = C=O >> C=C > {H} > Ar
Pd = C=C > {H} > C=O > Ar
Ru = C=O > C=C > Ar > {H}

{H} = hydrogenolysis
CX CH

Order of Alkene Reactivity

R
R

>

>

>

>
R

Note: many other factors involved (eg. the release of ring-strain)

Co-ordination of alkene on catalyst can lead to double bond isomerisation
Possibility of migration related to the degree of reversibility of co-ordination
Pd allows migration presumably via reversible co-ordination
Pt essentially binds irreversibly resulting in no isomerisation

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Stereoselectivity
Mechanism (vide supra) indicates the addition is predominanly syn
As substrate and hydrogen are both bound to surface addition occurs from the least
hindered face as more readily binds to surface)
Problem: isomerisation can lead to anti addition
Problem: predicting which face will bind to surface not as simple as above statement
suggests
Haptophilicity is the ability of a functional group to anchor to the surface and direct which
face of alkene co-ordinates
functional group

functional group
attracted to surface

normally hydrogen adds

from least hindered side

hydrogen adds
from opposite face

Alkynes
Lindlar catalyst (Pd / CaCO3 / PbO) optimum catalyst to prevent over-reduction and cis
/ trans isomerisation
syn addition
O

H2, Lindlar,
BuOH, rt
95 %

Heteroatom Hydrogenations
Carbonyl Moiety
Can be hydrogenated
Stereoselectivity hard to predict so prefer hydride reagents
Platinum reagents preferred as C=O faster than C=C (vide
supra) especially when poisoned
HO

CO2Et

HO

H2, PtO2,
AcOH, H2O

CO2Et
OH

Order of carbonyl reduction

O

>
R

Cl

>
R

R(H)

>
R

>
R

OR

>
R

OH

NH2

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Nitriles
OBn

OH

BnO

OBn

BocHN

N
Bn

H2, Pd(OH)2 / C,
MeOH

HO

OH

BocHN

NH2

N
H

Nitro Group
O

NH2

( )3

C4H 11
O

1. H2, Pd / C
2. (CO2H)2

( )3

C4H 11
O

O
C4H 11

( )3

N
H

Azides
N3

Ph
N

H 2N

H2. 5 % Pd / C

Ph
N

O
MeO 2C

MeO 2C

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Homogeneous Catalyst
Soluble in reaction medium
Mechanisms much better understood
Advantages: mild conditions (non-polar solvents which dissolve H2 better)
Advantages: less catalyst required (each molecule is available for reaction and not just surface)
Advantages: improved or complimentary selectivity (far more predictable)
Advantages: directed hydrogenations
Advantages: asymmetric hydrogenations
Alkene Hydrogenation
2 main types of homogeneous catalysts: dihydride and monohydride catalysts
Dihydride Catalysts
H
LnM

+ H2

LnM
H

Examples: Wilkinson's Catalyst ClRh(PPh3)3 (hydrogen adds prior to substrate)

Crabtree's Catalyst [Ir(COD)(PCy3)(pyr)]+PF6 (substrate adds before H 2)

General Mechanism

oxidative
cis addition
reductive
elimination

MLn
H

H2

reductive
elimination

LnM

MLn
H

Crabtree's
catalyst

Wilkinson's
catalyst
H
H

LnM H

LnM H

H2
LnM

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Monohydride Catalysts
LnMH
Examples: HRu(Cl)(PPh3)3
Cp2TiH

LnM H
LnM H

1,2-insertion
cis-addition

LnM H

reductive
elimination

metal centre
oxidised

Ln
M HH

LnM H

H2
oxidative addition

Wilkinson's Catalysis
Very well studied

S = solvent
or vacant site

S
P

Rh

Cl

catalytic
species

P
S

Rh+1
P
Rh+3
reductive elimination

S
P

Rh

H2

Cl

H
P
Cl

S
H
R

R1

H
P

oxidative addition

H
R2
R3

very fast; no
isomerisation
Rh+3

Rh

insertion
H
H

R
R1

Rh

Cl

R2
R3

R2
R3

RDS

P
Cl
R
R1

R
1
PR

Rh

H
P
R2
R3

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Selectivity
R1

>

Ar

( )n = 1,2

R1

>

>

R1

>

R1

>
R

R2

Like heterogeneous catalysts there is a strong steric selectivity for the least hindered alkenes
O

(CH2)3 CO2R
C5H 11

PO

(CH2)3 CO2R

ClRh(PPh3)3,
H2

C5H 11
H

PO

OP

OP

Stereoselectivity
As indicated in the mechanism reductive elimination is fast
so no isomerisation can occur and syn addition results
H
Ph

ClRh(PPh3)3,
D2

OMe

Ph

OMe

Like heterogeneous catalysts, hydrogenation occurs from the least hindered face
less substituted alkene
addition from least hindered side
ClRh(PPh3)3,
H2

iPr

TrO

iPr

ClRh(PPh3)3,
H2

OMe

TrO

OMe

Functional Group Compatibilty

Compatible with most functional groups
Aldehydes often undergo decarbonylation

N
Cbz

ClRh(PPh 3)3
95 %

N
Cbz

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Directed Hydrogenation
A hydroxyl group in the substrate can displace a ligand from the catalyst resulting in
directed hydrogenation
This can reverse normal selectivity
HO

HO

H2

same face

Cy3P

Ir

24 : 1
Crabtree's catalyst
Crabtree's catalyst much more reactive than Wilkinson's; so good for hindered alkenes
Crabtree's catalyst gives superior directing effect for cyclic substrates
For acyclic substrates use Wilkinson's catalyst
If alkene isomerisation a problem use Wilkinson's catalyst at elevated pressure
H
OH

H
H

OH

OH

vs

R
L

R
H
H

OH

anti

disfavoured due to
steric interactions
H

R
H

OH

OH

OH

vs

R
L

R
H

OH

syn

Note: only get stereocontrol if isomerisation is surpressed

ASYMMETRIC HYDROGENATION
Many asymmetric variants have now been developed
Diphosphine ligands are very common

MeO
CO2Me

+ H2 +
Ph

NHCOMe

Ph
Ar

> 95 % e.e.
P

Rh
Ph
S

Ph

CO2Me

NHCOMe

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Mechanism

most stable complex

CO2Me
H
N
P
P

Rh

CO2Me

O Ph

Ar

H2 slow
RDS
kmajor

H
P

fast

P
Rh

H
N

MeO 2C

CO2Me

H2 slow
RDS
kminor
H
N

MeO 2C

O Ph

H
Rh

PhO

H
P

O
P
H

P
P

minor

Ph

minor complex
reacts much faster

Rh

Ph O

Ar

kminor : kmajor 573 : 1

H
N

Rh

NHCOMe

+
Ph

major

Ph

fast

Rh

S NH
CO2Me

HN S
MeO 2C

Rh

P
H

P
Ph

Ph

the major product comes

from the minor complex
H

CO2Me
NHCOMe

MeO 2C
MeOCHN

Ph

Ph

minor

major

Note: Substrate and metal must be complexed to get good e.e.

Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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Non-Co-ordinated Asymmetric Catalysts

Catalysts that do not require co-ordination to the substrate to give good e.e.s still uncommon
They offer the advantage of greater structural variety
One example is:
MeO

MeO

Ph

3 mol% cat., H2 50 bar

99 % 98 % e.e.

Ph

BARF
O
Ph
Ph

BARF = tetrakis{3,5-trifluoromethyl}phenyl borate

Ir

tBu

Monohydride Catalyst
Provides a second example

Ti

1. BuLi
2. PhSiH3

Ti

N
R

H2 (80-500 psi)

N
H

68-89 %
95-99 % e.e.
X2 = 1,1'-binaphth-2,2'-diolate
R group in space

Mechanism

R
Ti

Ti

vs

Ti

R group clashes
with ligand

H
H N Ti

N
H

R
H

concerted 4-centre
cleavage of NTi
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Transfer Hydrogenation
free NH crucial

Ts
Ph

R
Ru

O
OH

Ph

N
H

OH

Cl

Mechanism is given in the Oxidation Section of this course

Problem: the reaction is reversible (hence the oxidation)
If formic acid / triethyl amine is used as the reductant reaction irreversible
O

O
N
H

cat.
Et3N

C
O

Hydrogenolysis
H2

NH

N
H

gives off CO2

hence irreversible

Used to remove various functional groups

I
O

OMe

H2, Ni[R]

H
I

Ph

OMe

Or protecting groups
OH

O
O

H2, Pd / C
O

Ease of reduction of functional groups towards catalytic hydrogenation

note how far
down benzyl
group is

RCOCl
RNO2
RCCR'

RCHO
RNH2
RCH=CHR'
RCH2OH

RCHO

Easiest

RCH2CH2R'

RCH=CHR'
RCOR'
ArCH2OR

RCHOHR'
ArCH3 + ROH

RCN

RCH2NH2

RCO2R'

RCH2OH + R'OH

Hardest
Note: different catalysts have different propensities
for functional groups so this is only a rough order
Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002

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