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

doi:10.6023/cjoc202004027

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (11): 3934-3943.DOI: 10.6023/cjoc202004027 Previous Articles Next Articles

Special Issue: 创刊四十周年专辑

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^a, 王楠^c, 齐越^a, 孙书涛^b, 刘希功^b, 李伟^a, 刘磊^b

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 发布日期:2020-05-20
通讯作者: 刘希功, 李伟, 刘磊 E-mail:201990000024@sdu.edu.cn;liwei6911@163.com;leiliu@sdu.edu.cn
基金资助:
国家自然科学基金（Nos.21722204，21971148）资助项目.

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

Wang Lin^a, Wang Nan^c, Qi Yue^a, Sun Shutao^b, Liu Xigong^b, Li Wei^a, Liu Lei^b

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:2020-04-17 Revised:2020-05-14 Published:2020-05-20
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21722204, 21971148).

1. cjoc202004027辅助材料.pdf(4268KB)

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

Cite this article

Wang Lin, Wang Nan, Qi Yue, Sun Shutao, Liu Xigong, Li Wei, Liu Lei. Synthesis of Sterically Hindered α-Aminonitriles through 1,6-Aza-conjugate Addition of Anilines to δ-Cyano Substituted para-Quinone Methides[J]. Chinese Journal of Organic Chemistry, 2020, 40(11): 3934-3943.

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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

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

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