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

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.