Page 160 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

asymmetric reduction using nonmetallic catalysts 147

Procedure

1. A 100 mL two-necked round-bottomed flask equipped with a magnetic
stirrer bar and an addition funnel were dried in an oven at 120 8C overnight.
The dry flask, equipped with the addition funnel, was placed under vacuum
until cool and then flushed with nitrogen.
2. The flask was charged with (S)-Me-CBS (1 M solution in toluene, 1.2 mL) in
10 mL of tetrahydrofuran. The mixture was cooled with an ice-bath and
then BH 3 :THF (6.7 mL) was added. The solution was stirred for 15 minutes.
3. The addition funnel was filled with acetophenone (1.16 mL) and dry tetra-
hydrofuran (5 mL); this solution was then added over 2 hours to the cold
reaction mixture.
4. After completion, the reaction was stirred for an additional 30 minutes at
room temperature.
5. The reaction was followed by TLC (eluent: petroleum ether±ethyl acetate;
75:25). The acetophenone was UV active, stained yellow with p-anisalde-
hyde, R f 0.68. Phenylethanol had a low UV activity, stained purple with
p-anisaldehyde, R f 0.46.
6. The reaction was quenched by careful addition of methanol (5 mL, hydrogen
evolution). An aqueous solution of hydrochloric acid 1N (10 mL) was then
added and a white suspension appeared. The mixture was stirred for 15 min-
utes.
7. Diethyl ether was added (30 mL) and the two-phase solution was transferred
into a separating funnel. The organic phase was separated and the aqueous
layer extracted with diethyl ether (2 20 mL). The combined organic layers
were washed with water (4 30 mL) and with brine (2 30 mL), dried over
magnesium sulfate, filtered and concentrated to give a yellow oil (1.64 g).
8. The residue was purified by Kugelrohr distillation giving the phenylethanol
as a colourless oil (1.1 g, 90 %).
The ee (95 %) was determined by chiral GC (Lipodex 1 E, 25 m, 0.25 mm
ID, temperatures: column 80 8C isotherm, injector 250 8C, detector 250 8C,
mobile phase helium). R t (S)-enantiomer: 68.3 min, R t (R)-enantiomer:
71.1 min.
1 H NMR (200 MHz, CDCl 3 ): d 7.18±7.36 (m, 5H, Ph); 4.87 (qd, J 6.6 Hz,
J 3.3 Hz, 1H, CHOH); 2.25 (br s, 1H, OH); 1.48 (d, J 6.6 Hz, 3H, CH 3 ).
ÿ1
IR (CHCl 3 , cm ): 3611, 3458 (O±H), 3011, 2981 (C±H Ar), 2889 (C±H
aliphatic), 1603 (Ar), 1493, 1453 (Ar), 1379 (Ar), 1255, 1075 (O±H), 895, 693
(Ar).
‡
Mass: calculated for C 8 H 10 O: m/z 122.07317, found [M] 122.07293.
Conclusion

The reduction using oxazaborolidine borane needs to be done in anhydrous
conditions to avoid the decomposition of the catalyst. The addition of aceto-
phenone has to be as slow as possible to obtain a good enantiomeric excess.
However, the reaction is easy to handle, the catalyst is commercially available