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
• hydrogenation
*H
H
• alkene adsorption
• alkene activation
*
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
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
• functional group
• functional group
attracted to surface
H
H
H
H
• 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
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
H
N
CO2Et
HO
H2, PtO2,
AcOH, H2O
O
H
CO2Et
OH
N
• Order of carbonyl reduction
O
O
O
>
R
Cl
O
O
>
R
R(H)
>
R
O
R
O
O
>
R
OR
>
R
OH
R
NH2
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Nitriles
OBn
OH
BnO
OBn
BocHN
N
Bn
C
H2, Pd(OH)2 / C,
MeOH
HO
OH
BocHN
NH2
N
H
N
Nitro Group
O
N
O
NH2
( )3
C4H 11
O
O
O
1. H2, Pd / C
2. (CO2H)2
( )3
C4H 11
O
O
O
C4H 11
O
O
( )3
N
H
Azides
N3
Ph
N
H 2N
H2. 5 % Pd / C
O
Ph
N
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)
General Mechanism
• oxidative
cis addition
reductive
elimination
MLn
H
H2
H
reductive
elimination
LnM
MLn
H
H
H
Crabtree's
catalyst
Wilkinson's
catalyst
H
H
LnM H
LnM H
H2
LnM
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Monohydride Catalysts
• LnM–H
• Examples: HRu(Cl)(PPh3)3
Cp2TiH
LnM H
LnM H
1,2-insertion
cis-addition
H
LnM H
H
reductive
elimination
• metal centre
oxidised
Ln
M HH
H
LnM H
H2
oxidative addition
Wilkinson's Catalysis
• Very well studied
• S = solvent
or vacant site
S
P
Rh
Cl
P
• catalytic
species
P
S
Rh+1
–P
Rh+3
• reductive elimination
S
P
Rh
S
H2
P
Cl
H
P
Cl
S
H
R
R1
H
P
S
• oxidative addition
H
R2
R3
• very fast; no
isomerisation
Rh+3
Rh
• insertion
H
H
P
R
R1
Rh
Cl
R2
R3
R2
R3
H
RDS
P
Cl
R
R1
R
1
PR
S
Rh
H
P
R2
R3
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Selectivity
R1
>
Ar
=
R
( )n = 1,2
R1
>
>
R
R1
>
R1
R
>
R
R
R2
• Like heterogeneous catalysts there is a strong steric selectivity for the least hindered alkenes
O
O
H
(CH2)3 CO2R
C5H 11
PO
H
H
(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
H
ClRh(PPh3)3,
D2
OMe
D
H
Ph
H
D
OMe
• Like heterogeneous catalysts, hydrogenation occurs from the least hindered face
• less substituted alkene
• addition from least hindered side
ClRh(PPh3)3,
H2
O
O
iPr
TrO
O
iPr
ClRh(PPh3)3,
H2
OMe
TrO
O
OMe
Functional Group Compatibilty
• Compatible with most functional groups
• Aldehydes often undergo decarbonylation
N
Cbz
O
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
O
N
O
H
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
L
R
H
H
L
M
OH
OH
vs
R
L
M
R
H
H
OH
R
anti
H
L
• disfavoured due to
steric interactions
H
L
R
H
OH
L
M
OH
OH
vs
R
L
M
R
H
OH
L
R
syn
H
• 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
H
> 95 % e.e.
P
P
S
Rh
Ph
S
Ph
CO2Me
NHCOMe
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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
P
Rh
S
S
H
N
MeO 2C
CO2Me
H2 slow
RDS
kminor
H
N
MeO 2C
O Ph
H
Rh
PhO
P
H
P
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
H
Ph
fast
O
Rh
S NH
CO2Me
HN S
MeO 2C
P
Rh
P
H
P
Ph
Ph
• the major product comes
from the minor complex
H
CO2Me
NHCOMe
MeO 2C
MeOCHN
Ph
Ph
minor
major
H
• 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
P
BARF = tetrakis{3,5-trifluoromethyl}phenyl borate
N
Ir
tBu
Monohydride Catalyst
• Provides a second example
X
Ti
R
1. BuLi
2. PhSiH3
X
Ti
H
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
H
N
Ti
H
vs
N
Ti
H
R
• R group clashes
with ligand
R
H
H N Ti
N
H
R
H
• concerted 4-centre
cleavage of N–Ti
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Transfer Hydrogenation
• free NH crucial
Ts
Ph
N
R
Ru
O
OH
Ph
+
N
H
OH
Cl
O
+
• 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
+
N
H
H
O
cat.
Et3N
R
X
R
C
O
Hydrogenolysis
H2
+
NH
N
H
• gives off CO2
hence irreversible
H
• Used to remove various functional groups
I
O
OMe
H2, Ni[R]
O
H
H
I
Ph
O
OMe
• Or protecting groups
OH
O
O
O
O
H2, Pd / C
O
R
O
R
Ease of reduction of functional groups towards catalytic hydrogenation
• note how far
down benzyl
group is
RCOCl
RNO2
RC≡CR'
RCHO
RNH2
RCH=CHR'
RCH2OH
RCHO
Easiest
RCH2CH2R'
RCH=CHR'
RCOR'
ArCH2OR
RCHOHR'
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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