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2014 , Vol. 34 >Issue 8: 1616 - 1622

DOI: https://doi.org/10.6023/cjoc201403004

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
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  • 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

  网络出版日期: 2014-04-18

基金资助

国家“十二五科技支撑计划”（No.2011BAE06A07-04）资助项目.

收起

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

  • Fu Xinghua ,
  • Fan Jianjian ,
  • Zou Aizong ,
  • Yu Juan ,
  • He Guangke ,
  • Zhu Hongjun
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  • College of Sciences, Nanjing Tech University, Nanjing 211816

Received date: 2014-03-03

  Revised date: 2014-03-31

  Online 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).

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摘要

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

本文引用格式

付行花 , 樊俭俭 , 邹爱宗 , 俞娟 , 何广科 , 朱红军 . 2-氮杂双环[3.1.0]己烷-3-羧酸的不对称合成[J]. 有机化学, 2014 , 34(8) : 1616 -1622 . DOI: 10.6023/cjoc201403004

Abstract

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

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