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.