相转移催化法和手性催化加氢法立体选择性地合成Fmoc保护的(S)-3,5-二溴苯丙氨酸  

Synthesis of Fmoc-protected (S)-3,5-Dibromophenylalanine in the Presence of a Phase Transfer Catalyst or a Chiral Catalyst

作　　者：王沁婷 赵帅[1] 金雷[1] 陈新[1] 

机构地区：[1]常州大学制药与生命科学学院,常州213164

出　　处：《有机化学》2016年第9期2242-2246,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金面上(No.21272029)资助项目~~

摘　　要：通过两种不对称催化方法合成了(S)-3,5-二溴苯丙氨酸.一种方法是以二苯亚胺甘氨酸叔丁酯和3,5-二溴苄基溴为底物,在O-烯丙基-N-9-蒽甲基溴化辛可宁定催化下,经不对称烷基化反应得到了(S)-3,5-二溴苯丙氨酸的衍生物,ee值达到94.9%,重点优化了不对称相转移催化烷基化反应的条件,得到了最优反应条件.另一种方法是以2-乙酰胺基-3-(3,5-二溴苯基)丙烯酸为底物,在双(1,5-环辛二烯)-三氟甲磺酸铑(I)和(R)-N-二苯基膦-N-甲基-(S)-2-(二苯基膦)二茂铁基乙胺催化下加氢得到乙酰基保护的(S)-3,5-二溴苯丙氨酸,再进行水解反应,最终得到(S)-3,5-二溴苯丙氨酸.经Fmoc的保护,得到Fmoc保护的(S)-3,5-二溴苯丙氨酸,ee值达到94.7%.所述两种方法中,第一种方法产率较高,对映选择性也较高,适合应用于其他手性二卤代苯丙氨酸的合成.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.

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 

分 类 号：O625.5[理学—有机化学]