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
收稿日期: 2016-01-31
修回日期: 2015-03-17
网络出版日期: 2016-04-07
基金资助
国家自然科学基金面上（No.21272029）资助项目.
Synthesis of Fmoc-protected (S)-3,5-Dibromophenylalanine in the Presence of a Phase Transfer Catalyst or a Chiral Catalyst
Received date: 2016-01-31
Revised date: 2015-03-17
Online published: 2016-04-07
Supported by
Project supported by the National Natural Science Foundation of China (No.21272029).
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.
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
王沁婷 , 赵帅 , 金雷 , 陈新 . 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[J]. 有机化学, 2016 , 36(9) : 2242 -2246 . DOI: 10.6023/cjoc201601045
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.
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