One-Pot Construction of Multiple Contiguous Chiral Centers Using Michael Addition of Chiral Amine

• Published in: Journal of organic chemistry Vol. 75; no. 12; pp. 4201 - 4211
• Main Authors: Ozeki, Minoru, Ochi, Shunsuke, Hayama, Noboru, Hosoi, Shinzo, Kajimoto, Tetsuya, Node, Manabu
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 18-06-2010
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Amines - chemical synthesis; Amines - chemistry; Chemistry; Esters - chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Preparations and properties; Stereoisomerism; Terpenoids; Michael addition; One pot reaction; Terpenoid; Cyclohexane derivatives; Hydroxyester; Nitrogen heterocycle; β-Lactams; Lactam; Chiral compound; Aldol condensation; Unsaturated compound; Ester; Terpene; Amine; Aminoester; Asymmetric synthesis; Benzylic compound; Monoterpene
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo1004586

Multiple contiguous chiral centers were constructed in one pot using three types of multistep reactions initiated with the Michael addition of N-benzyl-2(R)-methoxy-(+)-10-bornylamide to α,β-unsaturated esters, i.e., asymmetric Michael−aldol reaction, double Michael addition, and double Michael−aldol reaction. The chiral 2-methoxy-10-bornyl group as well as the benzyl group on the amino group of the products in the Michael−aldol reaction could be easily cleaved by treatment with NIS (4 equiv), and β-amino esters with multiple contiguous chiral centers were obtained in good yield. As an application, the β-amino-β′-hydroxy ester obtained in the asymmetric Michael−aldol reaction was converted to the β-lactam derivative in good yield.