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 H H H*
H*

• adsorption of H2
• predominantly syn
• alkene adsorption
• hydrogenation • alkene activation

*H * H* * H*
H * 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

{H} = hydrogenolysis
Pd = C=C > {H} > C=O > Ar
Ru = C=O > C=C > Ar > {H} 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

• functional group
• functional group attracted to surface
H
H
H
H

• normally hydrogen adds • hydrogen adds

from least hindered side from opposite face
Alkynes
• Lindlar catalyst (Pd / CaCO3 / PbO) optimum catalyst to prevent over-reduction and cis
/ trans isomerisation
• syn addition
O 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 CO2Et
H H
H2, PtO2,
O AcOH, H2O OH
N N

• Order of carbonyl reduction

O O O O O O O
> > > > >
R Cl R R(H) R O R R OR R OH R NH2

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 Nitriles
OBn OH
BnO OBn HO OH
H2, Pd(OH)2 / C,
BocHN
MeOH BocHN NH2
N C N
Bn N H

Nitro Group
O O NH2
N
1. H2, Pd / C ( )3
C4H 11
( )3 C4H 11
2. (CO2H)2 O O
O O O
O

O O
C4H 11 N ( )3
H
Azides
N3 Ph H 2N Ph

H2. 5 % Pd / C
N N
O O
MeO 2C MeO 2C

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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)

• oxidative General Mechanism

cis addition
reductive LnM reductive
elimination elimination
MLn MLn
H H H H H

H2 Wilkinson's Crabtree's
catalyst catalyst

H
H LnM H H2
LnM
LnM H

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 Monohydride Catalysts
• LnM–H
• Examples: HRu(Cl)(PPh3)3
Cp2TiH

LnM H
LnM H

1,2-insertion
cis-addition

H H LnM H
reductive
elimination

• metal centre
Ln
oxidised H M HH
LnM H

H2
oxidative addition

Wilkinson's Catalysis
• S = solvent • Very well studied
or vacant site
S
P P
Rh • catalytic
Cl P species
S

Rh+1
–P
Rh+3
• reductive elimination S H
P S H2 P H
Rh Rh
Cl P Cl P
S S
• oxidative addition
H H
R R2
R R2 R1 R3
R1 R3 • insertion
• very fast; no H R2 H
isomerisation H R3 P H
RDS Rh
P R Cl P
Rh+3 Rh 1 R R2
Cl PR
S R1 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 R1 R1

Ar > R
= > > R R1 > >
( )n = 1,2 R R R R2

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

O H O H
(CH2)3 CO2R (CH2)3 CO2R
ClRh(PPh3)3,
C5H 11 H2 C5H 11
H H
PO OP PO OP

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

H H H H
ClRh(PPh3)3, D D
D2
Ph OMe Ph OMe

• Like heterogeneous catalysts, hydrogenation occurs from the least hindered face
• less substituted alkene
• addition from least hindered side

O ClRh(PPh3)3, O
H2
iPr iPr

ClRh(PPh3)3,
TrO H2 TrO
O OMe O OMe

Functional Group Compatibilty

• Compatible with most functional groups
• Aldehydes often undergo decarbonylation

ClRh(PPh 3)3
N O
95 % N
Cbz 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 O
O H
Ir
N
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 L
R
OH H L M OH OH
H
R
vs R R
H
L M OH
H
L H anti
• disfavoured due to
steric interactions

H L
OH R L M OH OH
H
R
vs R
R
L M OH
H
L H 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 H
> 95 % e.e. CO2Me
+ H2 + Ph
P P
Ph NHCOMe Rh Ph NHCOMe
Ar Ph
S S

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 Mechanism

• most stable complex

CO2Me

H Ph NHCOMe H
N CO2Me MeO 2C N
fast fast
+
P P
Rh Rh
P O Ph Ph Ar Ph O P
P P
major Ar Rh Ph minor
S S
H2 slow H2 slow
RDS kminor : kmajor 573 : 1 RDS
kmajor kminor
H • minor complex H
H N CO2Me reacts much faster MeO 2C N H
H H
Rh Rh
P O Ph PhO P
P P

O O
P S NH HN S P
Rh CO2Me MeO 2C Rh
H H
P P
Ph Ph

• the major product comes

from the minor complex
CO2Me MeO 2C
H H
NHCOMe MeOCHN

Ph Ph
minor major

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

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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
3 mol% cat., H2 50 bar
Ph 99 % 98 % e.e. Ph

BARF
O
Ph BARF = tetrakis{3,5-trifluoromethyl}phenyl borate
P N
Ph Ir tBu

Monohydride Catalyst

• Provides a second example

R N
Ti
1. BuLi Ti
X X H R
2. PhSiH3 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 H
H N H N

• R group clashes
with ligand

R
H
R
N H N Ti H
H

• concerted 4-centre
cleavage of N–Ti
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 Transfer Hydrogenation
Ts • free NH crucial
Ph
N R
O Ru OH
OH N Cl O
Ph H
+ +

• 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
cat. +
N + H NH C
N H O Et3N N
H H O

Hydrogenolysis
• gives off CO2
H2
R X R H
hence irreversible

• Used to remove various functional groups

I
O OMe H2, Ni[R] O OMe

H H
I
• Or protecting groups
Ph O O OH O
H2, Pd / C
O O R O O R

Ease of reduction of functional groups towards catalytic hydrogenation

• note how far RCOCl RCHO Easiest

down benzyl RNO2 RNH2
group is RC≡CR' RCH=CHR'
RCHO RCH2OH
RCH=CHR' RCH2CH2R'
RCOR' RCHOHR'
ArCH2OR ArCH3 + ROH
RC≡N 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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