Asymmetric Michael Addition of α-Substituted Isocyanoacetates with Maleimides Catalyzed by Chiral Tertiary Amine Thiourea

• Published in: Journal of organic chemistry Vol. 77; no. 6; pp. 2947 - 2953
• Main Authors: Bai, Jian-Fei, Wang, Liang-Liang, Peng, Lin, Guo, Yun-Long, Jia, Li-Na, Tian, Fang, He, Guang-Yun, Xu, Xiao-Ying, Wang, Li-Xin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.03.2012; Amer Chemical Soc
• Subjects: Acetates - chemistry; Amines - chemistry; Catalysis; Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Isocyanates - chemistry; Maleimides - chemistry; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; Thiourea - chemistry; ORGANOCATALYTIC CYCLIZATION; CYANOACETATES; ENANTIOSELECTIVE CONJUGATE ADDITION; CONSTRUCTION; OXINDOLES; ISOCYANOESTERS; DERIVATIVES; ALPHA,ALPHA-DISUBSTITUTED ALDEHYDES; Michael addition; Agonist; Catalytic reaction; Maleimide derivative; Enantioselectivity; Nitrogen heterocycle; Bifunctional compound; Chiral compound; Thioureas; Diastereoselectivity; Imide; Asymmetric synthesis; Tertiary amine; Enantiomeric excess; Chemical synthesis; Isocyanide
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo2025288

A highly diastereoselective and enantioselective Michael addition of α-substituted isocyanoacetates with maleimides catalyzed by bifunctional tertiary amine thioureas has been developed. Various chiral succinimide derivatives bearing adjacent quaternary and tertiary stereocenters were prepared in excellent yields (up to 98%), diastereoselectivities (up to 99:1), and enantioselectivities (up to 98% ee). The synthetic utility of chiral succinimide derivatives is also demonstrated in the preparation of h5-HT1d receptor agonist motifs.