Chemistry Reference
In-Depth Information
Mechanism of Catalytic Asymmetric Hydrogenation
The reaction mechanism of the phosphine Rh complex-catalyzed hydrogenation has been elucidated by Halpern
[64], as also the mechanism of hydrogenation of an enamide, using a diphosphine yielding a phenylalanine
derivative as shown in Fig.
10
.
+
Ph
COOMe
+
Ph
P
P
S
NHCOMe
COOMe
Rh(I)
Rh(I)
NH
P
O
P
S
C
Me
2S
COOMe
*
S
- Ph
H
2
NHCOMe
+
+
Ph
CH
2
Ph
COOMe
S
P
C
P
Rh(III)
Rh(III)
COOMe
NH
NH
P
O
P
H
C
S
O
C
Me
Me
S=Solvent
Figure 10:
Mechanism of the Rh-diphosphine-catalyzed hydrogenation of an enamide.
First, solvent molecules (S) in the catalyst precursor are displaced by the olefinic substrate to form a chelate-Rh
complex in which the olefinic bond and the carbonyl oxygen interact with the Rh(I) centre. Hydrogen is oxidatively
added to the metal to form a Rh(III) dihydride intermediate. The two hydrogen atoms on the metal are successively
transferred to the carbon atoms of the coordinated olefinic bond by way of a five-membered chelate alkyl-Rh(III)
intermediate. The secondary binding of the carbonyl oxygen of the amide moiety results in a ring system that
stabilizes the reactive intermediate. Kinetic data suggest that, at roomtemperature, the oxidative addition of H
2
is
rate-limiting for the overall reaction. When an appropriate chiral phosphine ligand and proper reaction conditions
are chosen, high eantioselectivity is achieved. If a diphosphine ligand of
C
2
symmetry is used, two diastereoisomers
of the enamide coordination complex can be produced, because the olefin interacts with either the
re
face or the
si
face. This interaction leads to enantiomeric phenylalanine products via diastereoisomeric Rh(III) complexes.
Noyori's General Hydrogenation Catalysts
Noyori's discovery of the BINAP-Ru(II) complex catalysts was a major advance in stereoselective organic synthesis
[65]. The scope of the application of these catalysts is far reaching. These chiral Ru complexes serve as catalyst
precursors for the highly enantioselective hydrogenation of a range - and -unsaturated carboxylic acids [65].
An example is shown in Fig.
11
.
O
Ph
2
R
u
P
O
O
P
Ph
2
O
(
S
)-BINAP-Ru(OCOMe)
2
(0.5 mol%)
COOH + H
2
COOH
MeOH
MeO
MeO
(
S
)-Naproxen
92% yield, 97% ee
Figure 11
: The anti-inflammatory agent (
S
)-naproxen is produced in high yield and high eantiomeric excess using the Noyori's
catalyst.
This reaction, unlike Rh(I)-catalyzed olefin hydrogenation, proceeds via a metal monohydride mechanism. The
enantioselectivity is much higher in the use of the Rh catalyst and the sense of asymmetric induction is the opposite.
