Synthesis of Leiodolide A Macrolactone

Abstract

A convergent route toward the synthesis of leiodolide A (1) is described. Our studies explored reactions of the indium chloride-induced transmetalation of allylic stannane 32 for nucleophilic addition with nonracemic aldehyde 15. The stereoselective formation of the all-syn stereotriad was rationalized by an in situ isomerization to produce the Z-allylindium reagent for subsequent anti-Felkin addition. The inversion of C₁₇ stereochemistry led to an effective π-allyl Stille cross coupling utilizing Z-alkenylstannane 11b. The Horner-Wadsworth-Emmons reaction provides macrolactone 37 which exhibits discrepancies as compared with reported NMR data for the purported leiodolide A.