A Practical Asymmetric Synthesis of Isopropyl (1R,2S)-Dehydrocoronamate

作者：Tang Wenjun^*; Wei Xudong; Yee Nathan K; Patel Nitinchandra; Lee Heewon; Savoie Jolaine; Senanayake Chris H

来源：Organic Process Research & Development, 2011, 15(5): 1207-1211.

DOI：10.1021/op200038y

A novel asymmetric synthesis of isopropyl (1R,2S)-dehydrocoronamate is described from (S)-1,2,4-butanetriol as the starting material in 28% overall yield. Highlights of this synthetic route include selective cyclopropanation between chiral cyclic sulfate 5 and diisopropyl malonate (8c), formation of vinylcyclopropane 3c via elimination of halide 4c, selective monohydrolysis of diisopropyl ester 3c, and Curtius rearrangement of acid 10 to form isopropyl (1R,2S)-dehydrocoronamate TsOH salt 13 in >99% ee. With the involvement of only three isolations, this chromatography-free process provides a rapid and practical access to (1R,2S)-1-amino-2-vinylcyclopropane-1-carboxylic acid derivatives.

• 出版日期2011-10