Enantioselective copper-catalysed defluorinative alkylation of polyfluoroarenes with alkenes and 1,3-dienes

Abstract

Despite impressive advances in the field of defluorinative alkylation of polyfluoroarenes, the corresponding asymmetric counterpart has remained a formidable challenge. Herein, we present the first example of asymmetric defluorinative alkylation of polyfluoroarenes with readily accessible alkenes, 1,3-dienes, and even (Z/E)-mixed 1,3-dienes as potential nucleophiles in the presence of a chiral CuH catalyst, avoiding the conventional utilization of highly reactive organometallics. This method enables the efficient construction of the challenging chiral Csp³–C_ArF bond with outstanding stereocontrol (up to 99% ee in most cases). This reaction proceeds under mild reaction conditions, demonstrating excellent functional group compatibility and high regio- and stereoselectivity. Experimental studies in conjunction with density functional theory (DFT) calculations were carried out to unravel the plausible mechanism and elucidate the origins of excellent enantioselectivity.