Copper-Catalyzed Asymmetric Conjugate Addition of Alkene-Derived Nucleophiles to Alkenyl-Substituted Heteroarenes

Abstract

We herein report the copper-catalyzed asymmetric conjugate addition of β-substituted alkenyl heteroarenes, the one of most challenging Michael acceptors, with alkenes as the latent nucleophiles. Diverse chiral heteroarenes bearing two vicinal stereocenters were obtained in good to excellent yields, generally excellent enantioselectivity, and a good level of diastereoselectivity. The products of the Michael addition can be readily transformed into other valuable acyclic enantioenriched structures bearing three contiguous stereocenters via chiral amine catalysis. Mechanistic studies, including an isotope labeling experiment, a nonlinear effect study, kinetic isotope effect experiments, and initial-rate kinetics studies, were implemented, and the experimental results indicated that the hydrocupration step might be the turnover-limiting step. Moreover, the origin of preferential alkene hydrocupration in the presence of β-substituted alkenyl heteroarenes and the Ph-BPE-ligated CuH catalyst was also elucidated via some control experiments.