Page 163 - Catalysts for Fine Chemical Synthesis Vol 1 - Robert & Poignant

150 hydrolysis, oxidation and reduction

4. When the reaction was at reflux, a solution of chloroacetophenone (154 mg)
in toluene (2 mL) was added via a syringe pump over 10 minutes. After
completion of the addition the reaction was stirred for a further 20 minutes.
5. The reaction was followed by TLC (eluent: petroleum ether±ethyl acetate;
85:15). The chloroacetophenone was UV active and stained grey with p-
anisaldehyde dip, R f 0.5. 2-Chloro-1-phenylethanol was UV active and
stained green-grey with p-anisaldehyde, R f 0.39.
6. The mixture was cooled to room temperature and the borane±dimethylsul-
fide was slowly hydrolysed by water (10 mL) and then by a saturated
solution of NH 4 Cl (10 mL).
7. The mixture was transferred into a separating funnel and the two phases were
separated. The aqueous layer was extracted with ethyl acetate (2 30 mL).
The combined organic layers were washed with water (3 30 mL), brine
(3 30 mL) and then dried over magnesium sulfate, filtered and concentrated
to give a crude oil (620 mg).
8. The crude material was purified by flash chromatography on silica gel (30 g)
using petroleum ether±ethyl acetate±triethylamine (89:10:1) as eluent to give
2-chloro-1-phenylethanol as an oil (140 mg, 90 %).
The ee (95 %) was determined by chiral GC (Lipodex 1 E, 25 m, 0.25 mm
ID, temperatures: column 105 8C isotherm, injector 250 8C, detector 250 8C,
mobile phase helium). R t (R)-enantiomer: 102.4 min; R t (S)-enantiomer:
106.7 min.
1
H NMR (200 MHz, CDCl 3 ): d 7.39±7.31 (m, 5H, Ph); 4.88 (ddd, J
8.8 Hz, J 3.3 Hz, J 3.3 Hz, 1H, CH); 3.74 (dd, J 3.3 Hz, J 11.5 Hz, 1H,
CH a H b ); 3.70 (dd, J 8.8 Hz, J 11.8 Hz, 1H, CH a H b ); 2.78 (br s, 1H, OH).
ÿ1
IR (CHCl 3 , cm ): 3586, 3460 (O±H), 3070, 3012, (C±H Ar), 2961, 2897
(C±H aliphatic), 1603 (Ar), 1494, 1454 (Ar), 1428, 1385, 1254, 1187, 1062,
1012, 870, 690.
‡
Mass: calculated for C 8 H 9 OCl: m/z 156.03419, found [M] 156.03385.

Conclusion
The reduction using the oxazaphosphinamide is easy to reproduce and the
results correlate with the published material. During the reaction the addition
of the chloroacetophenone solution needs to be as slow as possible; this is an
essential factor for obtaining a good enantiomeric excess. According to the
publication, the reaction could be performed without the prescribed precau-
tions to work under anhydrous conditions with only a small drop in selectivity
and no change to the reaction time. This is due to the stability of the phosphi-
namide reagent, which is not sensitive to water or oxygen. Another advantage
of using this catalyst is that it does not decompose under the reaction condi-
tions and could be recovered and re-used without any decrease in the reactivity.
In Table 11.2 different results obtained by oxazaphosphinamide catalysts are
reported. Some other examples are given in Table 11.4.