Synthesis of Leiodolide A Macrolactone

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