Page 167 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

154 hydrolysis, oxidation and reduction

. Borane dimethylsulfide, 2 M in THF, 1.2 mL, 2.4 mmol, 1.2 eq
. Chloroacetophenone, 310 mg, 2 mmol
Chloroacetophenone is toxic and needs to be manipulated using gloves
and eye protection in a well-ventilated fume-hood.

. Aqueous solution of hydrochloric acid, 1 N, 3 mL
. Diethyl ether
. Aqueous solution of sodium hydroxide, 2 N, 20 mL
. Sodium sulfate
. p-Anisaldehyde dip

. 50 mL Two-necked round-bottomed flask with a magnetic stirrer bar
. Magnetic stirrer hot plate with a thermostatically controlled oil bath and
thermometer
. Syringe pump
. Syringe, 3 mL
. Separating funnel, 250 mL
. Kugelrohr apparatus

Procedure

1. A 50 mL round-bottomed flask equipped with a magnetic stirrer was dried
overnight at 150 8C and placed under vacuum and then flushed with nitro-
gen.
2. The flask was charged with the sulfoximine catalyst (68 mg) and dry toluene
(4 mL). To this white suspension was added borane dimethylsulfide (1.2 mL).
The mixture became clear with the evolution of hydrogen.
3. After 15 minutes a solution of chloroacetophenone (310 mg) in dry toluene
(2 mL) was added via a syringe pump over a period of 3 hours at room
temperature.
4. After completion of the addition the mixture was stirred for a further 10
minutes. The reaction was quenched with an aqueous solution of HCl (1 N,
3 mL) and water (10 mL).
5. The mixture was transferred into a separating funnel and the two phases
separated. The aqueous layer was extracted with diethyl ether (3 30 mL)
and the combined organic layers washed with an aqueous solution of
sodium hydroxide (2 N, 20 mL) and then dried over sodium sulfate, filtered
and concentrated.
6. The alcohol was obtained by distillation of the residue using a Kugelrohr
apparatus (120 8C, 3 mmHg) to give (S)-2-chloro-1-phenylethanol (233 mg,
1.49 mmol, 73 %).
The ee (82 %) was determined by chiral GC analysis (Lipodex 1 E, 25 m,
0.25 mm ID, temperatures: column 120 8C isotherm, injector 250 8C, detector
250 8C, mobile phase helium) R t (R)-enantiomer: 45.3 min, R t (S)-enantiomer:
46.5 min.