This document summarizes hydrogenation reactions using both heterogeneous and homogeneous catalysts. It discusses the mechanisms and selectivity of hydrogenation of alkenes, carbonyls, nitriles, nitro groups and azides using catalysts like platinum, palladium and rhodium. It also covers directed hydrogenation, asymmetric hydrogenation and transfer hydrogenation reactions. The order of reactivity for reducing different functional groups is provided.

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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
H H H H
H*
H*
H*
H*
**H
H***H
H
H
H
• catalyst surface
• adsorption of H2
• H2 disassociation / activation
• alkene adsorption
• alkene activation• hydrogenation
• predominantly syn
• 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
C–X → C–H
• Order of Alkene Reactivity
R
R
R
R R
R
R
R R
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
H
H
H
H
• normally hydrogen adds
from least hindered side
• hydrogen adds
from opposite face
• functional group
• functional group
attracted to surface
Alkynes
O
• Lindlar catalyst (Pd / CaCO3 / PbO) optimum catalyst to prevent over-reduction and cis
/ trans isomerisation
O
H2, Lindlar,
BuOH, rt
95 %
• syn addition
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
N
H
HO CO2Et
O
H2, PtO2,
AcOH, H2O
N
H
HO CO2Et
OH
• Order of carbonyl reduction
R Cl
O
R R(H)
O
R O R
O O
R OR
O
R OH
O
R NH2
O
> > > > >

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Nitriles
N
Bn
C
OBnBnO
OBn
BocHN
N
H2, Pd(OH)2 / C,
MeOH
N
H
OHHO
OH
BocHN NH2
Nitro Group
C4H11
OO
N
O O
O
( )3
C4H11
OO
NH2
O
( )3
N
H
C4H11
OO
( )3
1. H2, Pd / C
2. (CO2H)2
Azides
N
N3 Ph
O
MeO2C
H2. 5 % Pd / C
N
H2N Ph
O
MeO2C

4. 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
LnM + H2
H
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 H2)
General Mechanism
LnM
H
MLnMLn
H
LnM H
LnM
H
LnM H
HH HH
H2
H2
reductive
elimination
reductive
elimination
• oxidative
cis addition
Wilkinson's
catalyst
Crabtree's
catalyst

5. 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
• LnM–H
• Examples: HRu(Cl)(PPh3)3
Cp2TiH
LnM H
LnM H
LnM H
Ln
M HHH
LnM H
HH
1,2-insertion
cis-addition
reductive
elimination
Wilkinson's Catalysis
• Very well studied
Cl
Rh
P P
P
S
S
Cl
Rh
P S
P
S
S
Cl
Rh
P H
P
H
S
Cl
Rh
P H
P
H
R3
R1
R R2
Cl
Rh
P
P
H
S
R1
R
H
R3
R2
HH
R3
R1
R R2
R3
R1
R R2
H2
RDS
–P
Rh+1
Rh+3
Rh+3
• oxidative addition
• reductive elimination
H2
oxidative addition
• catalytic
species
• metal centre
oxidised
• insertion
• S = solvent
or vacant site
• very fast; no
isomerisation

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Selectivity
Ar R ( )n = 1,2 R
R1
R R1
R
R1
R
R1
R2
> > > > >=
• Like heterogeneous catalysts there is a strong steric selectivity for the least hindered alkenes
O
PO
C5H11
(CH2)3CO2R
OP
H
H
ClRh(PPh3)3,
H2
O
PO
C5H11
(CH2)3CO2R
OP
H
H
Stereoselectivity
• As indicated in the mechanism reductive elimination is fast
so no isomerisation can occur and syn addition results
Ph
H
OMe
H
ClRh(PPh3)3,
D2
OMePh
HH
DD
• Like heterogeneous catalysts, hydrogenation occurs from the least hindered face
O
iPr
ClRh(PPh3)3,
H2
O
iPr
• less substituted alkene
• addition from least hindered side
O
TrO
OMe
ClRh(PPh3)3,
H2
O
TrO
OMe
Functional Group Compatibilty
• Compatible with most functional groups
• Aldehydes often undergo decarbonylation
N
Cbz
O N
Cbz
ClRh(PPh3)3
95 %

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M
M
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
O
HO
O
H
N
Ir
Cy3P
Crabtree's catalyst
H2
24 : 1
• same face
• 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
R
OH
H
OH
R
H
H
L
L
R
H
H
OH
H
L
L
R
OH
R
OH
M
H
R
OH
H
L
L
M
H
OH
H
R
L
L
R
OH
vs
vs
• disfavoured due to
steric interactions
anti
syn
• Note: only get stereocontrol if isomerisation is surpressed
ASYMMETRIC HYDROGENATION
• Many asymmetric variants have now been developed
• Diphosphine ligands are very common
Ph
CO2Me
NHCOMe
+ H2 + P
Rh
P
S S
PhAr
Ph
MeO
Ph NHCOMe
H
CO2Me> 95 % e.e.

8. Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002
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Rh
Mechanism
H
N CO2Me
O PhP
P
Rh
H
NMeO2C
OPh P
P
Rh
H
N CO2Me
OPhP
H
H
P
Rh
H
P
O
P
S NH
Ph
CO2Me
Rh
H
NMeO2C
OPh P
H
H
P
Rh
H
P
O
P
SHN
Ph
MeO2C
Ph
H
NHCOMe
CO2Me
Ph
H
MeOCHN
MeO2C
Ph
CO2Me
NHCOMe
P
Rh
P
S S
PhAr
ArPh
+
fast fast
H2 slow
RDS
kmajor
H2 slow
RDS
kminor
minormajor
majorminor
kminor : kmajor 573 : 1
• most stable complex
• minor complex
reacts much faster
• the major product comes
from the minor complex
• Note: Substrate and metal must be complexed to get good e.e.

9. 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:
P N
O
tBuIr
Ph
Ph
BARF
Ph
MeO
3 mol% cat., H2 50 bar
99 % 98 % e.e. Ph
MeO
BARF = tetrakis{3,5-trifluoromethyl}phenyl borate
Monohydride Catalyst
• Provides a second example
TiX X
X2 = 1,1'-binaphth-2,2'-diolate
Ti H
NR
N
H
R
1. BuLi
2. PhSiH3 H2 (80-500 psi)
68-89 %
95-99 % e.e.
Ti H
Ti HN
R
Ti HN
R
Ti HN
R
H
H
vs
N
H
R
Mechanism
• R group in space
• R group clashes
with ligand
• concerted 4-centre
cleavage of N–Ti

10. Gareth Rowlands (g.rowlands@sussex.ac.uk) Ar402, http://www.sussex.ac.uk/Users/kafj6, Reduction and Oxidation 2002
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R
Transfer Hydrogenation
O
OH
+
OH
O
+
N
ClN
HPh
Ph
Ts
Ru
• free NH crucial
• 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
N
H
N
H O
O
H+
N
H
NH +
O
C
O
cat.
Et3N
• gives off CO2
hence irreversible
Hydrogenolysis
R X R H
H2
O
I
OMe
H
I
H2, Ni[R] O OMe
H
• Used to remove various functional groups
• Or protecting groups
O O R
OPh O
H2, Pd / C
O O R
OH O
Easiest
Hardest
RCOCl RCHO
RNO2 RNH2
RC≡CR' RCH=CHR'
RCHO RCH2OH
RCH=CHR' RCH2CH2R'
RCOR' RCHOHR'
ArCH2OR ArCH3 + ROH
RC≡N RCH2NH2
RCO2R' RCH2OH + R'OH
Ease of reduction of functional groups towards catalytic hydrogenation
• note how far
down benzyl
group is
• Note: different catalysts have different propensities
for functional groups so this is only a rough order