Construction of enantioenriched eight-membered lactones via Pd-catalyzed asymmetric (6+2) dipolar annulation

作者：Wang, Bao-Cheng; Wei, Yi; Xiong, Feng-Ya; Qu, Bao-Le; Xiao, Wen-Jing; Lu, Liang-Qiu^*

来源：Science China Chemistry, 2022, 65(12): 2437-2443.

DOI：10.1007/s11426-022-1374-4

• asymmetric catalysis
• dipolar annulation
• eight-membered lactone
• ketene
• palladium

Concise synthesis of eight-membered lactones, a kind of medium-sized heterocycles widespread in many bioactive natural products, is highly significant. However, it still remains a challenge due to unfavorable entropic factor and transannular interaction. Herein, we disclose an enantioselective synthesis of eight-membered lactones through a Pd-catalyzed asymmetric (6+2) dipolar annulation of vinyl oxetanes and alpha-diazo ketones (20 examples, up to 93% yield and 95:5 er). This reaction features simple operation, mild conditions and good enantiocontrol, especially the challenging chiral all-carbon quaternary stereocenter. A newly developed chiral hybrid P,S ligand and the in-situ photo-generation of ketene dipolarophiles are crucial to this success.

• 单位
  中国科学院; 中国科学院研究生院