Diastereoselective Synthesis of γ-Lactones through Reaction of Sulfoxonium Ylides, Aldehydes, and Ketenes: Substrate Scope and Mechanistic Studies

In this article, we describe the synthesis of gamma-lactones through the reaction of sulfoxonium ylides, aldehydes, and disubstituted ketenes. The one-pot sequential method provides access to gamma-lactones from disubstituted ketenes, in moderate to excellent yields, and with good diastereoselectivity favoring the trans-diastereomer (dr up to 92 : 8). The reaction mechanism was investigated by performing labeling, crossover, and various control experiments. The results of those experiments support the reaction mechanism involving betaine formation, reaction of the betaine with a ketene to form an enolate intermediate, [3,3]-sigmatropic rearrangement of an enolate intermediate, and finally, 5-exo-tet cyclization to afford the gamma-lactone product.