辛可宁季铵盐的合成及催化不对称烷基化研究  

Synthesis of Cinchonine Quaternary Ammonium Salts and the Catalysis of Asymmetric Alkylation

作　　者：李智[1] 廉明明[1] 孟庆伟[1] 

机构地区：[1]大连理工大学制药科学与技术学院,精细化工国家重点实验室,大连116012

出　　处：《高等学校化学学报》2010年第8期1564-1569,共6页Chemical Journal of Chinese Universities

摘　　要：探索了辛可宁季铵盐的通用合成方法,确定辛可宁与取代苄溴在四氢呋喃中回流为最优反应途径,合成了11个羟基保留的辛可宁季铵盐,收率57%～88%,并合成了4种羟基保护季铵盐,羟基成醚过程在生成季铵盐前后均可进行,总收率62%～71%;羟基酯化只能在生成季铵盐之后进行,总收率78%.本文共合成了15个季铵盐(Cn-1～Cn-15),其中5个为新化合物,另有4个的合成方法未见文献报道.选用该类季铵盐催化剂催化二苯亚甲基甘氨酸叔丁酯的不对称苄基化反应,结果发现,催化剂苄基具有4-Br取代或羟基成醚均有助于提高反应产物的对映选择性.Cn-9可得到最优的反应结果,产率93%,e.e.值91%.Eleven catalysts bearing a free hydroxyl group were prepared by direct N-alkylation with corresponding substituted benzyl bromides under a reflux condition in good yields（57%—88%）.Other 4 catalysts with the chiral secondary alcohol protected by allyl,benzyl,propynyl and benzoyl were synthesized via two steps.The ether group at the phase-transfer catalysts could be approached before or after the N-benzylation reaction.In contrast,the hydroxyl group was changed to benzoic acid ester when the quaternary ammonium salt had been prepared.Fifteen phase-transfer catalysts were gotten,and 5 catalysts of them had never been reported.Then,various catalysts were screened for alkylating reactivity of glycine imine ester.Cinchonine derived catalysts Cn-9 proved to be highly reactive in 93% yield with 91% e.e.value.

关 键 词：辛可宁 季铵盐 相转移催化剂 不对称烷基化反应 

分 类 号：O621[理学—有机化学]