Polysubstituted Piperidines via Iodolactonization: Application to the Asymmetric Synthesis of (+)-Pseudodistomin D

Abstract

Conjugate addition of lithium (S)-N-allyl-N-(α-methyl-p-methoxybenzyl)amide to methyl (E,E)-hepta-2,5-dienoate furnished the corresponding β-amino ester. N-Protecting group manipulation, ring-closing metathesis, and ester hydrolysis gave enantiopure [N(1')-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-2'-yl]ethanoic acid. Subsequent iodolactonization gave a bicyclic iodolactone scaffold. This key intermediate was elaborated to (+)-pseudodistomin D [in >99% ee and 7% yield over 16 steps from methyl (E,E)-hepta-2,5-dienoate].