Synthesis of Axially Chiral Biaryls via Pd(II)-Catalysed Direct C(sp2)-H Olefination and Arylation

Herein, two efficient reaction protocols for the construction of axially chiral biaryls via Pd-catalysed direct C-H functionalization of 1-arylisoquinoline N-oxides through kinetic resolution have been uncovered. The atroposelective C-H olefination of 1-arylisoquinoline N-oxides is achieved with alkenes such as acrylates, styrenes, phenylvinyl sulfone, acrylonitrile, and maleimides, while the arylation is successfully attained with iodoarenes. The commercially available, cost-effective, and bench-stable chiral mono-protected amino acid is successfully utilized as the chiral ligand to achieve atroposelective products via kinetic resolution. The high conformational stability of the axially chiral products in different solvents and at high temperatures, as observed from the experimental studies and DFT calculations, shows their excellent stability. A plausible mechanism has been proposed based on the preliminary mechanistic studies, which were further evidenced by DFT calculations.