Achiral Pyridine Ligand-Enabled Enantioselective Radical Oxytrifluoromethylation of Alkenes with Alcohols

Abstract

A conceptually novel strategy with achiral pyridine as the ancillary ligand to stabilize high-valent copper species for the first asymmetric radical oxytrifluoromethylation of alkenes with alcohols under Cu^I /phosphoric acid dual-catalysis has been developed. The transformation features mild reaction conditions, a remarkably broad substrate scope and excellent functional group tolerance, offering an efficient approach to a wide range of trifluoromethyl-substituted tetrahydrofurans bearing an α-tertiary stereocenter with excellent enantioselectivity. Mechanistic studies support the presumed role of the achiral pyridine as a coordinative ligand on copper metal to stabilize the key transient reaction species involved in the asymmetric induction process.

Keywords: achiral ligands; alkene oxytrifluoromethylation; asymmetric catalysis; copper; radical reactions.