Catalytic hydrogenation
Wilkinsons catalyst
The complex RhCl(PPh3)3 (also known as Wilkinsons catalyst) became the first highly active homogeneous hydrogenation catalyst that compared in rates with heterogeneous counterparts. Wilkinson, J. Chem. Soc. (A) 1966, 1711.
Ph3P PPh3 Rh Cl Ph3P
1-octene
H2 (1 atm), RT Benzene
octane
Wilkinsons catalyst
Wilkinsons catalyst is compatible with a range of functional groups because the mechanism does not involve hydride ion transfer.
O O OR O OH
C N
NO2
OR
But ethylene is not hydrogenated due to formation of a strongly bonded ethylene complex.
+
Cl PPh3 Rh PPh3 Ph3P Cl PPh3 Rh Ph3P
H2C=CH2
-PPh3
However, ethylene reacts with the preformed dihydride complex. This implies that the dihydride formation precedes olefin complexation in the catalytic cycle.
2 H2C=CH2
H Cl PPh3 Rh Ph3P H PPh3
-PPh3
Cl PPh3 Rh Ph3P
H3C-CH3
Hydrogenation mechanism
Wilkinsons catalyst, RhCl(PPh3)3 is used in benzene/ethanol solution in which it dissociates to some extent; a solvent molecule (Solv) fills the vacant site: RhCl(PPh3)3 + Solv ' RhCl(Solv)(PPh3)2 + PPh3
HH H C C R HH PPh3 Cl Rh Solv H2
(4)
PPh3 H H2C R Rh Cl
PPh3 16-e
(1)
PPh3 H H Rh Cl
PPh3
CH H 16-e
(3)
H H PPh3 Cl Rh PPh3 18-e
(2)
PPh3 16-e R
Steps: (1) H2 addition, (2) alkene addition, (3) migratory insertion, (4) reductive elimination of the alkane, regeneration of the catalyst. Halpern, Chem. Com. 1973, 629; J. Mol. Cat. 1976, 2, 65; Inorg. Chim. Acta. 1981, 50, 11. 4
Wilkinsons catalyst selectivity
The rate of hydrogenation depends on (a) presence of a functional group in the vicinity of the C=C bond and (b) degree of substitution of the C=C fragment.
Increasing rate
A polar functional group may accelerate catalysis by assisting olefin coordination to Ru
Terminal C6-C12 alkenes are hydrogenated at the same rate Conjugated dienes react slower
Hydrogenation of internal and branched alkenes is the slowest (note: cis is faster than trans!)
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Wilkinsons catalyst selectivity
Hydrogenation is stereoselective:
Cl PPh3 Rh PPh3 Ph3P D2 benzene, rt
Cl PPh3 Rh Ph3P PPh3 C3H7 CH3 D2 benzene, rt C3H7 CH3
H HO2C
H CO2H
D H HO2C
D H CO2H
D + hexane
meso compound, major product
cis: trans > 20:1
Rh preferentially binds to the least sterically hindered face of the olefin:
less hindered Cl PPh3 Rh PPh3 Ph3P H2 benzene/EtOH, rt H Ph3P Cl Rh H PPh3 + R H R endo CH2H R=H : 73% endo R=Me : 92% endo H R exo
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H Ph3P Cl Rh H PPh3 R
R more hindered
CH2H
Wilkinson, J. Chem. Soc. (A) 1966, 1711 Rousseau, J. Mol. Cat. 1979, 5, 163. Jardine, Prog. Inorg. Chem. 1981, 28, 63.
Wilkinsons catalyst selectivity
Site selectivity: Preferential hydrogenation of the least sterically hindered C=C bonds (note that heterogeneous hydrogenation catalysts are often not selective):
cis-disubstituted
O O O
Pd/C acetone, H2 (1 atm) rt, 75%
Cl PPh3 Rh Ph3P PPh3 O H
O O
O O O
tetrasubstituted
C6H6/EtOH, H2 (1 atm) rt, 95%
Pedro, JOC 1996, 61, 3815.
Cis-disubstituted C=C react faster than trans-disubstituted C=C:
cis-disubstituted
O CO2Me HO Cl PPh3 Rh PPh3 Ph3P O CO2Me
OAc
H2 (1atm), benzene/EtOH, rt, 80%
HO
OAc
trans-disubstituted
Schneider, JOC 1973, 38, 951.
Wilkinsons catalyst selectivity
Site selectivity Directing group effects:
OH Cl PPh3 Rh Ph3P PPh3 H MeO KOR, H2 (6.8 atm), benzene, 50 C, 68% MeO OH
OK
PPh3 O PPh3 Rh H H
cis-isomer (exclusive) note: a mixture of cis and trans isomers resulted with Pd/C
MeO
MeO
Base-assisted formation of the alkoxide resulted in displacement of the chloride ligand and directed olefin complexation.
Thompson, JACS 1974, 96, 6232. Jardine, Prog. Inorg. Chem. 1981, 28, 63
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Cationic catalysts
Cationic catalysts are the most active homogeneous hydrogenation catalysts developed so far:
PPh3 Rh PPh3
Ir
PPh3 N
Cl PPh3 Rh Ph3P PPh3
Schrock-Osborn catalyst
Substrates
Crabtrees catalyst
TOF 4000 6400
Wilkinsons catalyst
700
10
4500
650
3800
13
4000
Catalytically active species
With bidentate ligands, olefin coordination can precede oxidative addition of H2 (S = methanol, ethanol, acetone).
Ph2 P P Ph2
Rh
H2 solvent = S
Ph2 P S Rh S P Ph2
H Ph2 P S Rh H P S Ph2
only species observed by NMR in the absence of olefin
unobservable
With monodenate ligands, the hydrogenation may involve formation of a dihydride intermediate:
PPh3 PPh3 H2 PPh3 S Rh S Ph3P H2 H PPh3 S Rh Ph3P H S
Rh
solvent = S
Catalyst precursor
unobservable intermediate
Only species observable by NMR
The difference is due to the strong trans-influence of hydride and phosphine ligands, which make unfavorable a trans H-M-PR3 structural arrangement. 10 Halpern, JACS 1977, 99, 8055; Schrock & Osborn, JACS 1976, 98, 2134.
Halperns mechanism of hydrogenation for cationic Rh catalysts with bidentate phosphines
Ph R NHAc Ph HN R H Ph 2 P Rh P O S Ph2 Ph Ph2 RP NH Rh P O Ph2 S Rh S P Ph2 Ph2 P R = CO2Me Ph R
NHAc
(E)-methyl 2-acetamido3-phenylacrylate
observed by NMR
Ph H Ph2 P R Rh P H O Ph2
observed by NMR
H2 rate-detrmining step
HN
Steps: (1) alkene addition, (2) H2 addition, (3) migratory insertion, (4) reductive elimination of the alkane, regeneration of the catalyst. Halpern, Science 1982, 217, 401.
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Cationic catalysts: substrate-directed hydrogenation
The unsaturated cationic catalysts can bind a ligating group of the substrate in addition to the olefin. This bidentate coordination determines the selectivity of hydrogenation:
OH Ir PCy3 N OH H Me OH Me H
2.5 mol%
Me
6-isopropyl-3methylcyclohex-2-enol
CH2Cl2, H2 (1atm), rt
64 : 1
2-isopropyl-5-methylcyclohexanol
Intermediate:
Hoveida, Chem. Rev. 1993, 93, 1307.
H Cy3P Py Ir OH H Me
i
Pr
Other functionalities also direct:
OH OH
Me
Me
H2 / Ir cat. 97%
Me Me H
Me
Me
H2 / Ir cat. >99%
Me Me H Me
H2 / Ir cat. >99%
Me H
56 : 1
124 : 1
999 : 1
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Asymmetric hydrogenation
A bidentate, C2 symmetric version of the cationic Schrock-Osborn catalyst affords high levels of enantioselectivity in the hydrogenation of achiral enamides. This was the first demonstration that a chiral metal complex could effectively transfer chirality to a non-chiral DIPAMP - chiral (C2) substrate.
Knowles, JACS 1975, 97, 2567.
Ph CO2H NHAc
(E)-2-acetamido-3phenylacrylic acid
MeO P Rh P
diphosphine
OMe
(S)-2-acetamido-3-phenylpropanoic acid
Ph
CO2H NHAc
H2 (1 atm), rt i-PrOH, >99% yield
93 % ee
A variety of bidentate chiral diphosphines have been synthesized and used to make amino acids by hydrogenation of enamides:
PPh2 PPh2
PPh2 PPh2
PPh2 PPh2
O O
PPh2 PPh2
Chiraphos
NORPHOS
R
SKEWPHOS
DIOP
PPh2 PPh2
P R P R H H
PPh2 PPh2
Fe
NMe2 PPh2 PPh2
For review on DuPhos: Burk, Acc. Chem. Res 2000, 33, 363.
BINAP
DuPHOS
BICP
JOSIPHOS
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H2-hydrogenation and transfer hydrogenation of C=O (ketones, aldehydes) and C=N (imines) bond
The catalytic hydrogenation of polar C=O and C=N bonds are key reactions in fine chemical and pharmaceutical synthesis. A very important group of catalysts operate by hydride transfer to the substrate in the outer coordination sphere of the complex. Hydrogen can come from H2 or from an organic donor, such as 2-propanol.
H2 hydrogenation: Transfer hydrogenation:
R1R2C=Q + H2 R1R2CH-QH R1R2C=Q + DH2 R1R2CH-QH + D
e.g. DH2 = (CH3)2CH-OH and D = (CH3)2C=O
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Metal-ligand bifunctional catalysts.
Noyori has coined the term metal-ligand bifunctional catalysts, describing systems containing an ancillary ligand cis to the hydride that assists in the hydride transfer step and this ligand must have an NH or OH (protic) group.
Steps: (I) substrate addition (outer sphere), (II) simultaneous hydride and proton transfer, (III) H2 addition, (IV) regeneration of the catalyst.
Morris, Coord. Chem. Rev. 2004, 248, 2201-2237.
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Enantioselective hydrogenation of polar bonds
Ruthenium complexes containing chiral diphosphine (e.g. (R)-binap) and diamine (e.g. (R,R)-diamine) ligands are very efficient enantioselective hydrogenation catalysts:
Only the S-form of the alcohol is produced
Note: Only trans-RuH2 are active catalysts, because of the strongly hydridic nature of transdihydrides.
Morris, Coord. Chem. Rev. 2004, 248, 2201-2237.
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Structures of the intermediate species
18-e trans-dihydride
16-e amido-hydride
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Noyoris transfer hydrogenation catalysts
Very efficient for enantioselective transfer hydrogenation.
Noyori, Acc. Chem. Res. 1997, 30, 97; JACS 2000, 122, 1466; JOC 2001, 66, 7931
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Intermediates in Noyoris transfer hydrogenation
18-e hydride
16-e amido complex
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