Synthesis of the C1–C12 acid fragment of amphidinolide T marine macrolides via SmI 2-mediated enantioselective reductive coupling of aldehydes with a chiral crotonate

Abstract

A new strategy for enantioselective assembly of the trisubstituted tetrahydrofuran ring has been established for synthesis of the C1–C12 acid fragment of amphidinolide T series marine macrolides. The key steps involve the SmI 2-mediated highly enantioselective reductive coupling of an aldehyde with the (1 S,2 R)- N-methylephedrine-derived crotonate to form the cis-3,4-disubstituted γ-butyrolactone and the subsequent BF 3-mediated 1,3- anti-selective allylation of the five-membered-ring oxocarbenium ion with allyltrimethylsilane. The desired C1–C12 acid fragment was obtained in >25% overall yield via a 9-step sequence.