Page 140 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

asymmetric reduction of ketones 127

. Magnetic stirrer bar
. Rotary evaporator
. Chromatography column (200 mL)

Procedure

1. In a glass autoclave equipped with a magnetic stirrer bar were placed BisP*±
RuBr 2 (52 mg), methyl 3-oxopentanoate (10.7 g), and degassed methanol/
water (10/1) 200 mL under an argon atmosphere.
2. Then argon gas was replaced with hydrogen. The hydrogenation was per-
2
formed at 70 8C under 6 kg/cm of hydrogen for 10 hours.
3. The solvent was removed under reduced pressure and the residue was
purified by chromatography on silica gel (chloroform:acetone ˆ 3:1) to
afford (R)-(ÿ)-methyl 3-hydroxypentanoate (10.4 g, 96 %, 98 % ee) as a
colourless oil.
The ee (98 %) was determined by HPLC (CHIRALCEL OD, flow rate
0.5 mL/min, eluent n-hexane/2-propanol ˆ 95/5); (R)-enantiomer: R t
13.8 min, (S)-enantiomer: R t 28.4 min.
1
H NMR (400 MHz, CDCl 3 ): d 0.97 (3H, t, J 7.4 Hz), 1.48±1.58 (2H, m),
2.41 (1H, dd, J 9.1 and 16.4 Hz), 2.53 (1H, dd, J 3.0 and 16.4 Hz), 2.91 (1H, br
s), 3.72 (3H, s), 3.95 (1H, m).
ÿ1
IR (neat, cm ): 3443 (OH), 2965, 2881, 1738 (CˆO), 1439, 1284, 1172,
1113, 1068, 1015, 983.

Conclusion
The asymmetric hydrogenation with BisP*±RuBr 2 may be applied to a wide
range of b-ketoesters, b-ketoamides, and b-ketophosphonates. Table 9.2 shows
typical examples.

9.5 (1S, 3R, 4R)-2-AZANORBORNYLMETHANOL, AN EFFICIENT
LIGAND FOR RUTHENIUM CATALYSED ASYMMETRIC TRANSFER
HYDROGENATION OF AROMATIC KETONES

Diego A. Alonso and Pher G. Andersson

DepartmentofOrganicChemistry,UppsalaUniversity,Box531,S-75121Uppsala,Sweden.
Asymmetric ruthenium-catalysed hydrogen transfer from 2-propanol to ketones
is an efficient method for the preparation of optically active secondary alco-
hols [41] . Very recently, a new catalytic system has been developed based on
ruthenium complexes having 2-azanorbornylmethanol as the chiral ligand
(Figure 9.2), and their efficiency as catalysts for the enantioselective transfer
hydrogenation of aromatic ketones has been demonstrated, affording the cor-
responding secondary alcohols with high rates and excellent ee's [42] .