Iridium-Catalyzed Regiodivergent Atroposelective C–H Alkylation of Heterobiaryls with Alkenes

The atroposelective direct C–H alkylation of heterobiaryls
with simple alkenes represents a challenging and underexplored frontier.
Herein we report an iridium(I)-catalyzed regiodivergent and enantioselective
C–H alkylation of 1-arylisoquinolines or 2-arylpyridines with
alkenes. By utilizing a cationic iridium catalyst with different types
of chiral bidentate phosphine ligands, both linear- and branched-selective
C–H alkylations were achieved with high regioselectivities
and enantioselectivities. With this atom-economic and ligand-enabled
regiodivergent protocol, a series of axially chiral nitrogen-containing
heterobiaryls were synthesized with good efficiency and high enantioselectivity.
For the linear-selective alkylation involving the styrene moiety,
computational investigations illuminated that the regioselectivity
is established during the migratory insertion step of styrene into
the Ir–C bond. Both experimental and density functional theory
(DFT) studies concerning the substituent effects of the styrene moiety
were also conducted. These results suggest the primacy role of the
resonance effect relative to the field-inductive effect in determining
the regioselectivity of this transformation.