【作者】 李智；

【导师】 孟庆伟；

【作者基本信息】 大连理工大学 ， 药物化学， 2010， 硕士

【摘要】 不对称相转移催化烷基化反应是不对称形成C-C键的重要方法之一,本文研究了辛可宁衍生相转移催化剂的制备及催化二苯亚甲基甘氨酸叔丁酯不对称烷基化过程,主要研究内容如下：通过苯甲醛还原-溴化、卤素置换、苄胺水解-溴化、NBS溴化4种方法合成了14个取代苄基溴化物,产率38%～97%,并确定了取代苯甲醛还原-溴化法为取代苄基溴的最佳制备方法。实验发现金鸡纳碱与取代苄溴在四氢呋喃中回流为最佳的金鸡纳碱季铵盐制备方法,用该方法合成了11个金鸡纳碱季铵盐,和5个羟基保护的金鸡纳碱季铵盐,收率在57%～88%之间,产物经1H-NMR、13C-NMR、HRMS、比旋光、熔点表征,其中6个未见文献报道。选用16个金鸡纳碱季铵盐为不对称相转移催化剂催化二苯亚甲基甘氨酸叔丁酯的不对称烷基化过程,发现催化剂分子结构中的苄基具有4-Br取代基,或金鸡纳碱的羟基被醚化后其产物的对映选择性提高。以Cn-15为催化剂,对二苯亚甲基甘氨酸叔丁酯进行不同烷基化,可达95%产率,96%e.e.。更多还原

【Abstract】 The Asymmetric alkylation catalyzed by phase-transfer catalysts is one of the most important methods for establishing a C-C bond. This dissertation mainly focuses on the synthesis of cinchonine derivatived quaternary ammonium salts and the phase-transfer catalysis of the glycine imine ester asymmetric benzylation reaction.14 Substituted benzylbromides were synthesized by 4 different methods:benzaldehyde reduction-bromination, benzyl chloride halogen metathesis, benzylamine hydrolyzation-bromination, NBS bromination, yields 38%～97%. The benzaldehyde reduction-bromination was the best method for achieving substituted benzylbromide.We optimized the synthetic condition of cinchonine derivatived quaternary ammonium salts.11 catalysts bearing a free hydroxyl group and 5 catalysts with the chiral secondary alcohol protected were prepared by direct N-alkylation with corresponding substituted benzyl bromides under a reflux condition in 57%～88%yields. These quaternary ammonium salts identified by 1H-NMR,13C-NMR, HRMS, specific rotation and melting point.6 of them were novel compounds.16 catalysts were screened for alkylation of glycine imine ester using benzyl bromide. We found that the catalyst bearing an 4-Br benzyl group or the hydroxyl group protected by ether moiety could increase both the yield and e.e.. Cinchonine derived catalyst Cn-15 proved to be highly reactivity and selectivity, and up to 95%yield with 96%e. e..更多还原