关键词: (S)-3,5-二溴苯丙氨酸, 相转移催化, 不对称催化氢化, 烷基化

Two methods of catalytic asymmetric synthesis of (S)-3,5-dibromophenylalanine are presented. One approach is to use asymmetric alkylation reaction starting from diphenylimine glycine tert-butyl ester and 3,5-dibromobenzyl bromide, with O-allyl-N-9-anthracene methyl bromide cinchonidine as phase-transfer catalyst, the (S)-3,5-dibromophenylalanine derivative was obtained (up to 94.9% ee). The optimized conditions of asymmetric phase transfer catalytic alkylation are explored. Another method is to employ asymmetric hydrogenation starting from 2-acetylamino-3-(3,5-dibromophenyl)acrylic acid with bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate and (R)-diphenylphosphino-N-methyl-1-[(S)-2-diphenyl-phos-phino)ferrocenyl]ethylamine[(R)-methyl BoPhoz] as chiral catalyst. (S)-3,5-Dibromophenylalanine hydrochloride was obtained after hydrolysis. By Fmoc protection, Fmoc-(S)-3,5-dibromophenylalanine was obtained (up to 94.7% ee). By comparison of the two methods, the first one gives higher overall yield and a little bit better selectivity, and is more suitable for the synthesis of other chiral dihalo-substituented phenylalanine derivatives.

Key words: (S)-3,5-dibromophenylalanine, phase transfer catalyst, asymmetric catalytic hydrogenation, alkylation