有机化学 ›› 2014, Vol. 34 ›› Issue (8): 1616-1622.DOI: 10.6023/cjoc201403004 上一篇    下一篇

研究论文

2-氮杂双环[3.1.0]己烷-3-羧酸的不对称合成

付行花, 樊俭俭, 邹爱宗, 俞娟, 何广科, 朱红军   

  1. 南京工业大学理学院 南京 211816
  • 收稿日期:2014-03-03 修回日期:2014-03-31 出版日期:2014-08-25 发布日期:2014-04-18
  • 通讯作者: 朱红军 E-mail:zhuhj@njtech.edu.cn
  • 基金资助:
    国家“十二五科技支撑计划”(No.2011BAE06A07-04)资助项目.

Asymmetric Synthesis of 2-Azabicyclo[3.1.0]hexane-3- carboxylic Acid

Fu Xinghua, Fan Jianjian, Zou Aizong, Yu Juan, He Guangke, Zhu Hongjun   

  1. College of Sciences, Nanjing Tech University, Nanjing 211816
  • Received:2014-03-03 Revised:2014-03-31 Online:2014-08-25 Published:2014-04-18
  • Supported by:
    Project supported by the National Key Technology R&D Program of the Ministry of Science and Technology (No. 2011BAE06A07-04).

设计了以D-谷氨酸或L-谷氨酸为原料,经氨基保护、4-二甲氨基吡啶(DMAP)催化环合、还原脱水成烯、不对称Simmons-Smith反应、水解,高立体选择性合成2-氮杂双环[3.1.0]己烷-3-羧酸的路线. 用1H NMR,13C NMR,单晶X衍射等对中间体及目标产物进行了结构表征. 优化了DMAP催化环合、Simmons-Smith和水解反应的工艺条件,结果表明,DMAP催化环合反应在原料比为n(DMAP):n(二碳酸二叔丁酯):n(吡啶)=0.40:4.0:1.0条件下,(R)-5-氧代吡咯-1,2-二甲酸二叔丁酯的收率可达82%;Simmons-Smith反应随着反应时间延长,顺式结构与反式结构含量比不断变化,直到反应时间为19.5 h时,顺式与反式达到最佳比为6:1,收率为75%. 总收率达30%,de值72%.

关键词: 2-氮杂双环[3.1.0]己烷-3-羧酸, 谷氨酸, DMAP催化环合, 水解反应, 不对称合成

2-Azabicyclo[3.1.0]hexane-3-carboxylic acids were obtained via amino protection, 4-dimethylaminopyridine (DMAP) catalytic cyclization, reduction-dehydration into alkene, asymmetric Simmons-Smith reaction and hydrolysis reaction from glutamic acid. The intermediates and target products were characterized by 1H NMR and 13C NMR. (1R,3S,5R)- 2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid and (1S,3S,5S)-2-(tert-butoxycarbonyl)-2-azabicyclo-[3.1.0]hexane-3-carboxylic acid were analyzed by X-ray diffraction as well. The process conditions about DMAP catalytic cyclization reaction, Simmons-Smith reaction and hydrolyzation were discussed. The results show that the yield of (R)-1,2-di-tert-butyl 5-oxopyrrolidine- 1,2-dicarboxyate was 82% at the ratio of n(DMAP):n(di-tert-butyl dicarbonate):n(pyridine)=0.40:4.0:1.0. The ratio of cis/trans-form varied with the reaction time in Simmons-Smith reaction, which gave a best ratio of 6:1 at 19.5 h. The total yield is 30%, and the de value is 72%.

Key words: 2-azabicyclo[3.1.0]hexane-3-carboxylic acid, glutamic acid, DMAP catalytic cyclization, hydrolysis reaction, asymmetric synthesis