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
6

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

13

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

17

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

18

Intermediates in Noyoris transfer hydrogenation

18-e hydride

16-e amido complex

19