Nickel/Photoredox-Catalyzed Enantioselective α-Aminoalkylation of 2-Iodopyridines

Chiral Ni-PHOX complexes in combination with photoredox catalysis are shown to be effective to achieve the asymmetric coupling of amino acids with 2-iodopyridines at the C2-position. The regio- and enantioselective protocol developed herein enables direct access to chiral pyrid-2-yl β-aminoalcohols, which are found in many active pharmaceutical ingredients. This methodology can be extended to other heteroarenes, such as quinolines and azines, on one gram scale. Computational studies supported by experimentation revealed the trend of ligand steric and electronic influences on enantioselectivity. A plausible mechanism was proposed using DFT to further rationalize the observed regio- and enantioselectivity.