HFIP-Promoted Regioselective Hydrofunctionalization of Enamides and <i>N</i>-Vinyl Azoles

An efficient and regioselective method for the intermolecular hydrofunctionalization of enamides and <i>N</i>-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 <i>NH</i>-free indoles, pyrroles, and carbazoles as nucleophiles, proceeding via a Markovnikov-selective hydrofunctionalization pathway. The protocol is general and simple with broad substrate compatibility.