Page 154 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

asymmetric reduction using bakers' yeast 141

Materials and equipment

. Immobilized Bakers' Yeast, 200 g
. Sucrose, 40 g
. N-CBZ-3-Ketoproline ethyl ester, 5.64 g
. Ethanol, 10 mL
. Celite
. 2 L Erlenmeyer flask
. Magnetic stirrer
. Dropping funnel
. Buchner funnel

Procedure
1. The beads from the previous procedure ( 200 g) were placed into a 2 L
Erlenmeyer flask containing a large magnetic bar. Distilled water was
added to give 950 mL total volume. Sucrose (40 g) was added and the
mixture was allowed to stir vigorously for 30 minutes after which time a
solution of the keto ester (5.64 g, 20 mmol) in ethanol (10 mL), was added
over a period of 3 hours. The reaction was monitored by TLC and stopped
when most of the starting material had been consumed (no longer than 24
hours).
2. The aqueous liquid was decanted onto a bed of Celite in an 11 cm Bu Èchner
funnel. The remaining yeast beads were washed and decanted three times
using ethyl acetate (200 mL portions). The beads were then pressed free of
their liquid content by compression against the filter. The resulting yeast
cake was rinsed with ethyl acetate ( 100 mL) and the layers of the filtrate
were then separated. The aqueous layer was saturated with sodium chloride,
filtered through Celite to remove gelatinous emulsions, and then extracted
with ethyl acetate (200 mL). The combined organics were dried over magne-
sium sulfate, filtered, and evaporated to give 5.53 g of the crude product.
3. The crude product may be purified by chromatography over silica gel (eluted
with 1:1 ethyl acetate±hexane). Average purified yield 85 %. R f 0.35 (50:50
hexane:ethyl acetate).
The optical purity and stereochemistry was established by conversion to
the known N-BOC protected proline and by comparison of spectral data
[6]
and rotation values . Additionally, the optical purity was established by
HPLC analysis of the 3,5-dinitrobenzoates on a Pirkle column and by
Mosher ester analysis.
1
H NMR (400 MHz, CDCl 3 ): d 1.24±1.30 (m, 3H), 2.02±2.12 (m, 2H),
2.65 (s, 1H, broad), 3.53±3.58 (m, 1H), 3.69±3.73 (m, 1H), 4.08±4.15 (m,
1H), 4.22±4.26 (m, 1H), 4.41±4.46 (m, 1H), 4.59±4.62 (m, 1H), 5.04±5.19 (m,
2H), 7.29±7.36 (m, 5H).
13
C NMR (100 MHz, CDCl 3 ): d 14.0 and 14.1, 32.0 and 32.8, 44.2 and
44.4, 61.2 and 61.3, 63.5 and 63.8, 67.1, 71.4 and 72.2, 127.7 and 127.8, 127.9