Macrocyclic Lactone Formation through Sulfide Contraction: Synthesis of (±)-Diplodialide A

A methodology for the synthesis of macrocyclic β-ketolactones from ω-hydroxythioamides is described. The hydroxythioamides were esterified with chloroacetyl chloride, and the resulting chloroesters underwent Eschenmoser sulfide contraction when treated with sodium iodide, diisopropylethylamine, and triethyl phosphite in acetonitrile. The β-ketolactones were obtained in 25-58% yield. The utility of the method was demonstrated by the synthesis of diplodialide A.