Diastereoselective Synthesis of γ‐Lactones through Reaction of Sulfoxonium Ylides, Aldehydes, and Ketenes: Substrate Scope and Mechanistic Studies. Issue 1 (9th December 2020)

• Record Type: Journal Article
• Authors: Peraino, Nicholas J.; Mondal, Mukulesh; Ho, Han‐Jen; Beuque, Antoine; Viola, Evan; Gary, Melanie; Wheeler, Kraig A.; Kerrigan, Nessan J.
• Is Part Of: European journal of organic chemistry. Issue 1(2021)
• Page Start: 151
• Page End: 160
• Publication Date: 2020-12-09
• Subjects: Betaines -- Cumulenes -- Diastereoselectivity -- Lactones -- Ylides; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202001233
• Languages: English
• ISSNs: 1434-193X

Abstract

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. Abstract : The reaction of sulfoxonium ylides, aldehydes, and disubstituted ketenes provides access to γ ‐lactones in moderate to excellent yields with moderate to good diastereoselectivity favoring the trans ‐diastereomer (dr up to 92 : 8). A [3, 3]‐sigmatropic rearrangement is proposed to be the key mechanistic step.