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Chinese Journal of Organic Chemistry >

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

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

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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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 . DOI: 10.6023/cjoc202004027

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