Coordinating activation strategy enables 1,2-alkylamidation of alkynes

Abstract

The radical 1,2-difunctionalization reaction of alkynes has been evolved into a versatile approach for expeditiously increasing the complexity of the common feedstock alkyne. However, intermolecular 1,2-carboamidation with general alkyl groups is an unsolved problem. Herein, we show that a coordinating activation strategy could act as an efficient tool for enabling radical 1,2-alkylamidation of alkynes. With the employment of diacyl peroxides as both alkylating reagents and internal oxidants, a large library of β-alkylated enamides is constructed in a three-component manner from readily accessible amides and alkynes. This protocol exhibits broad substrate scope with good functional group compatibility and is amenable for late-stage functionalization of natural molecules and biologically compounds.