Asymmetric
reductive three-component arylalkylation of alkenes
via the radical relay method has been well established, while asymmetric
arylalkylation via the migratory insertion strategy remains unexplored.
We report enantioselective nickel-catalyzed cross-electrophile arylalkylation
of alkenes with aryl- and alkyl halides via an integrated Heck carbometalation/radical
cross-coupling sequence. This protocol employing a chiral Ni/PHOX
catalytic system allows terminal and internal alkenes to successfully
engage the arylalkylation with exquisite control of regio-, chemo-,
and stereoselectivity. More importantly, this reductive arylalkylation
undergoes regio- and enantioselective arylnickelation followed by
radical cross-coupling via Csp3–Csp3 reductive
elimination, thus exhibiting reverse regioselectivity to the radical
relay method. Mild reaction conditions and exceptional functional
group tolerance facilitate this method’s compatibility with
bioactive motifs and the modular synthesis of biologically active
compounds. The control experiments and density functional theory calculations
provide insights into the mechanism and origin of regio- and stereoselectivity,
and the hemilabile nature of the PHOX ligand is critical for achieving
this enantioselective arylalkylation.