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

Abstract

In this article, we describe the synthesis of γ‐lactones through the reaction of sulfoxonium ylides, aldehydes, and disubstituted ketenes. The one‐pot sequential method provides access to γ‐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 γ‐lactone product.

Asymmetric transformations from sulfoxonium ylides

“…[28][29][30][31][32][33][34][35][36] Important progress has also been made with regards to metal or carbenefree reactions by exploring the potential nucleophilicity of the sulfoxonium ylides. Some representative examples are the insertion reactions, [37][38][39] a-halogenations, 40 alkylations, 41 cyclizations, [42][43][44][45] ring CH 2 -homologations and epoxide ring opening reactions (Scheme 2H-L). [46][47][48] With respect to the asymmetric transformations, the reactions of the sulfoxonium ylides still lack research compared to the sulfonium ylides.…”

“… 28–36 Important progress has also been made with regards to metal or carbene-free reactions by exploring the potential nucleophilicity of the sulfoxonium ylides. Some representative examples are the insertion reactions, 37–39 α-halogenations, 40 alkylations, 41 cyclizations, 42–45 ring CH 2 -homologations and epoxide ring opening reactions ( Scheme 2H–L ). 46–48 …”