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


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

  1. 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;;
  • 基金资助:

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

Wang Lina, Wang Nanc, Qi Yuea, Sun Shutaob, Liu Xigongb, Li Weia, Liu Leib   

  1. 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).

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