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

摘要

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 andα-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.