HFIP-Promoted Regioselective Hydrofunctionalization of Enamides and N-Vinyl Azoles

An efficient and regioselective method for the intermolecular hydrofunctionalization of enamides and N-vinyl azoles has been developed, enabling the formation of diverse C–S, C–O, C–N, and C–C bonds. This transition-metal-free, additive-free, and Brønsted acid-free protocol employs hexafluoroisopropanol (HFIP) as the sole reagent, which plays a dual role: formation of iminium carbocation intermediate and facilitating nucleophile generation through its hydrogen-bonding network. The reaction demonstrates exceptional substrate versatility, accommodating thiophenols, alcohols, heterocyclic amines, as well as NH-free indoles, pyrroles, and carbazoles as nucleophiles, proceeding via a Markovnikov-selective hydrofunctionalization pathway. The protocol is general and simple with broad substrate compatibility.