含未保护羟基2-吡咯烷酮衍生物的直接还原氰基化：N-甲基-2-别-Bulgecinine的立体选择性合成

doi:10.6023/cjoc201703024

有机化学 ›› 2017, Vol. 37 ›› Issue (5): 1189-1197.DOI: 10.6023/cjoc201703024 上一篇下一篇

研究论文

含未保护羟基2-吡咯烷酮衍生物的直接还原氰基化：N-甲基-2-别-Bulgecinine的立体选择性合成

高燕娇, 肖振华, 刘良先, 黄培强

福建省化学生物学重点实验室能源材料化学协同创新中心厦门大学化学化工学院化学系厦门 361005

收稿日期:2017-03-13 修回日期:2017-04-01 发布日期:2017-04-10
通讯作者: 刘良先,黄培强 E-mail:lxliu@xmu.edu.cn;pqhuang@xmu.edu.cn
基金资助:
国家自然科学基金（No.21332007）和教育部长江学者和创新团队发展计划资助项目.

Direct Reductive Cyanation of A 2-Pyrrolidinone Chiral Building Block Bearing An Unprotected Hydroxyl Group: A Stereoselective Synthesis of N-Methyl-2-epi-bulgecinine

Gao Yanjiao, Xiao Zhenhua, Liu Liangxian, Huang Peiqiang

Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Centre of Chemistry for Energy Materials, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005

Received:2017-03-13 Revised:2017-04-01 Published:2017-04-10
Contact: 10.6023/cjoc201703024 E-mail:lxliu@xmu.edu.cn;pqhuang@xmu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21332007) and the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education.

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1. 含未保护羟基2-吡咯烷酮衍生物的直接还原氰基化：N-甲基-2-别-Bulgecinine的立体选择性合成.PDF(1405KB)

摘要/Abstract

报道手性合成砌块（4S，5R）-N-苄基-4-苄氧基-5-羟甲基-2-吡咯烷酮（3a）的直接还原氰基化及产物的立体化学与转化研究.含未保护羟基的内酰胺用LiAlH₄/KCN体系直接还原氰基化，生成比例为69：31的2，5-反式/顺式非对映立体异构体.与文献类似结果对比显示，氰基负离子对5-羟甲基-D-1-吡咯啉鎓中间体的加成主要受立体电子效应和C（5）位取代基（羟甲基）与进攻试剂间烯丙型1，3-位阻控制.该混合物在碱性条件下水解，生成比例为10：90的2，5-反式/2，5-顺式-bulgecinine衍生物.这一结果表明氰基水解反应伴随着在C（2）位发生了有合成价值的串联差向异构化.由此建立了立体选择性地合成2，5-顺式（-）-N-甲基-2-别-bulgecinine的简便方法.

关键词: 酰胺, 腈类化合物, 亚胺鎓离子, 立体选择性合成, 差向异构化

The direct reductive cyanation of N-benzyl-4-benzyloxy-5-hydroxymethyl-2-pyrrolidinone (3a), a lactam bearing a free hydroxyl group, has been achieved with the LiAlH₄/KCN combination. The reaction afforded 2,5-trans-2-cyano-5-hydroxylmethyl-4-benzyloxy-pyrrolidine (5a) and its cis-diastereomer 5b in a ratio of 69:31 with a combined yield of 63%. The observed 2,5-trans-stereoselectivity is suggested to be resulted from both stereoelectronic effect and allylic 1,3-strain between the hydroxymethyl group at C(5) and the incoming cyanide anion on the presumed Δ-1 pyrrolinium ion intermediate. The subsequent hydrolysis of the cyano group of the diastereomeric mixture 5a/5b (trans:cis=69:31) under basic conditions afforded the corresponding 5-hydroxymethyl-4-benzyloxyproline with 2,5-cis-diastereomer as the major diastereomer (trans:cis=10:90). This result implies that a synthetically useful epimerization at C(2) has occurred concomitantly. This unexpected result afforded a concise and highly stereoselective synthesis of 2,5-cis-(-)-N-methyl-2-epi-bulgecinine.

Key words: amides, nitriles, iminium ion, stereoselective synthesis, epimerization

引用此文

高燕娇, 肖振华, 刘良先, 黄培强. 含未保护羟基2-吡咯烷酮衍生物的直接还原氰基化：N-甲基-2-别-Bulgecinine的立体选择性合成[J]. 有机化学, 2017, 37(5): 1189-1197.

Gao Yanjiao, Xiao Zhenhua, Liu Liangxian, Huang Peiqiang. Direct Reductive Cyanation of A 2-Pyrrolidinone Chiral Building Block Bearing An Unprotected Hydroxyl Group: A Stereoselective Synthesis of N-Methyl-2-epi-bulgecinine[J]. Chin. J. Org. Chem., 2017, 37(5): 1189-1197.

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含未保护羟基2-吡咯烷酮衍生物的直接还原氰基化：N-甲基-2-别-Bulgecinine的立体选择性合成

Direct Reductive Cyanation of A 2-Pyrrolidinone Chiral Building Block Bearing An Unprotected Hydroxyl Group: A Stereoselective Synthesis of N-Methyl-2-epi-bulgecinine

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