Regioselective Hydroarylation of Ynamides: A Direct Synthetic Route to Trisubstituted Enamides

Trisubstituted enamides are commonly found in natural products, pharmaceuticals, and functional materials. A general method for synthesizing trisubstituted enamides is the hydroarylation of ynamides. A metal-free, atom-efficient, regioselective 1,2-hydroarylation of ynamides is herein demonstrated using an arene as a coupling partner. The reaction exhibits a broad substrate scope and tolerates ynamides derived from biologically relevant molecules, highlighting its synthetic utility. In addition, the hydroarylated products can be readily transformed into diverse functional molecules, demonstrating the versatility of this approach.