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2020 , Vol. 40 >Issue 11: 3934 - 3943

DOI: https://doi.org/10.6023/cjoc202004027

研究论文

基于δ-腈基取代对亚甲基苯醌1,6-氮杂共轭加成的大位阻α-氰胺合成研究

  • 王琳 ,
  • 王楠 ,
  • 齐越 ,
  • 孙书涛 ,
  • 刘希功 ,
  • 李伟 ,
  • 刘磊
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  • a 山东中医药大学药学院 济南 250355;
    b 山东大学化学与化工学院 济南 250100;
    c 山东省肿瘤防治研究院(山东省肿瘤医院) 山东第一医科大学(山东省医学科学院) 济南 250117

收稿日期: 2020-04-17

  修回日期: 2020-05-14

  网络出版日期: 2020-05-19

基金资助

国家自然科学基金（Nos.21722204，21971148）资助项目.

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Synthesis of Sterically Hindered α-Aminonitriles through 1,6-Aza-conjugate Addition of Anilines to δ-Cyano Substituted para-Quinone Methides

  • Wang Lin ,
  • Wang Nan ,
  • Qi Yue ,
  • Sun Shutao ,
  • Liu Xigong ,
  • Li Wei ,
  • Liu Lei
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  • a Department of Pharmaceutical Analysis, School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355;
    b School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100;
    c The First Ward of Intervention Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117

Received date: 2020-04-17

  Revised date: 2020-05-14

  Online published: 2020-05-19

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 21722204, 21971148).

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摘要

目前对亚甲基苯醌参与的1，6-共轭加成反应的研究主要集中在对预先合成的δ-单取代底物进行三级碳中心的构建.报道了一级芳胺对预先制备的δ-氰基-δ-芳基二取代对亚甲基苯醌的1，6-氮杂共轭加成反应，高效地合成了一系列含有四级碳手性中心的大位阻胺类化合物.该方法条件温和、反应迅速，同时芳胺和对亚甲基苯醌的适用范围广泛.此外，环状二级胺例如吗啉和咪唑也是合适的亲核试剂.

关键词： 对亚甲基苯醌; δ-氰基-δ-芳基二取代; 大位阻胺; 氮杂四级碳中心; 1,6-氮杂共轭加成

本文引用格式

王琳 , 王楠 , 齐越 , 孙书涛 , 刘希功 , 李伟 , 刘磊 . 基于δ-腈基取代对亚甲基苯醌1,6-氮杂共轭加成的大位阻α-氰胺合成研究[J]. 有机化学, 2020 , 40(11) : 3934 -3943 . DOI: 10.6023/cjoc202004027

Abstract

Current 1,6-conjugate addition typically focused on pre-synthesized para-quinone methides bearing a δ-mono substituent for tertiary stereocenter formation. Here, an efficient 1,6-aza-conjugate addition of primary anilines to pre-prepared δ-CN-δ-aryl disubstituted para-quinone methides for facile access to sterically hindered amines with a fully substituted α-car-bon center has been described. The mild and expeditious method exhibited broad scopes of both aniline and para-quinone methide components. The generality of the method in modular preparation of medicinally valuable, sterically hindered amines was further demonstrated by using cyclic secondary amines like morpholine and imidazole as nucleophilic components.

Key words： para-quinone methide; δ-CN-δ-aryl disubstitution; sterically hindered amine; aza-quaternary carbon; 1,6-aza-conjugate addition

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