Expeditious synthesis and applications of isoquinoline ring-modified Quinap derivatives

Abstract

A wide range of isoquinoline ring-modified Quinap oxides with different steric and electronic variations have been constructed through a palladium-catalyzed imidoylative cyclization of arylethenyl isocyanides with 2-diphenylphosphinyl-1-naphthyl bromides. The Pd-catalysis plays dual roles in the formation of both axial C–C bond and isoquinoline ring. This de novo synthetic strategy features good functional group tolerance, high yields and easy scale-up, providing Quinap derivatives with substitution patterns that could not be obtained using coupling reactions. Chiral ligands 7 and 12 can be readily prepared by transformation of the resulting Quinap oxide to their BINOL esters, and have been proven to be superb chiral ligands for the copper-catalyzed enantioselective A³-coupling and alkynylation of quinoline reactions. In general, the enantioselectivies obtained using ligands 7 and 12 are excellent, and the ee values are higher than those using Quinap as ligand, even three times higher in some cases. Mechanism studies revealed that a monomeric copper(I) complex bearing a single chiral ligand was formed and served as the catalytically active species.