Synthesis of the C1–C12 acid fragment of amphidinolide T marine macrolides via SmI2-mediated enantioselective reductive coupling of aldehydes with a chiral crotonate

• DOI: 10.1016/j.tet.2009.06.070
• Publication Date: 2009-06-25T10:21:41Z
• Authors: Jialu Luo; Huoming Li; Jinlong Wu; Xinglong Xing; Wei-Min Dai
• Keywords: Tetrahydrofuran; Oxocarbenium

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 SmI2-mediated highly enantioselective reductive coupling of an aldehyde with the (1S,2R)-N-methylephedrine-derived crotonate to form the cis-3,4-disubstituted γ-butyrolactone and the subsequent BF3-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.