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

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.