Visible light-promoted copper catalyzed regioselective acetamidation of terminal alkynes by arylamines

Abstract

Herein, we describe a copper photoredox catalyzed synthesis of acetamide via regioselective C–N coupling of arylamines with terminal alkynes using molecular oxygen (O₂) as an oxidant at room temperature under visible light irradiation (47 examples). Unique simultaneous formation of both amide and ester functionalities occurs via intramolecular cyclization in a single-step reaction in the case of anthranilic acids using inexpensive copper as a catalyst and eco-friendly O₂ as an oxidant and reagent. Different substrates undergo different reaction pathways to generate similar acetamide products, as evidenced by ¹⁸O₂ labelling experiments. The current protocol was also applied for the rapid, few step preparation of biologically active inhibitors (BACE-1 and PDE4). This process can be readily scaled up to a gram scale, and calculations of green metrics suggest the economic feasibility and eco-friendly nature of the current photoredox approach.