Synthesis of Leiodolide A Macrolactone
David R Williams1, Fese M Okha1, Sarah A Ward1
1Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.
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.
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