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

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.