Work

Cu(II)-Catalyzed Hydrofunctionalization of Unactivated Alkynes via π-Lewis Acid Activation

Year: 2025

Type: article

Abstract: A copper(II)-catalyzed stereodivergent hydrooxygenation of electronically unactivated alkynes with carboxylic acids is reported. Regioselectivity and kinetic reactivity are facilitated by a bidentate auxiliary, and syn - or anti -stereoselectivity is controlled through the judicious tuning of reaction conditions. The method affords trisubstituted E - or Z -alkenes with an enol ester functionality in a highly selective manner. Beyond carboxylic acids, a variety of other OH- and NH-nucleophiles react smoothly to furnish enol ether, enamine, and alkylidene β-lactam building blocks. Mechanistic experiments and density functional theory (DFT) calculations shed light on the nature of π-Lewis acid activation with Cu(II) and support a catalytic cycle that features an inner-sphere nucleocupration mechanism via a six-membered transition state for syn -addition and a base-assisted outer-sphere nucleocupration mechanism for anti -addition.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c10387