Oxidant-Free Amidation of Aldehydes Enabled by Electrophotocatalysis

An electrophotocatalytic method for C(sp²)–N bond formation via radical-polar crossover (RPC)-HAT catalysis is presented. The mild operating conditions enable functionalization of a wide range of compounds, with electricity as the sole oxidant.

Electrophotocatalysis (EPC) is emerging as a powerful tool in organic synthesis, offering unique redox transformations without the need for sacrificial oxidants or reductants. Building on this activation mode, we have developed an electrophotocatalytic method for the direct amidation of aldehydes, utilizing electricity and protons as oxidants and light to generate chlorine radicals for hydrogen atom transfer (HAT). This sustainable approach is compatible with a wide range of aldehydes and nitrogen-based nucleophiles, performing efficiently under batch conditions and demonstrating scalability with flow technology. The mild reaction conditions, adequate functional group tolerance, and versatility make this EPC protocol particularly suitable for C─N bond formation, enabling functionalization of diverse organic compounds and facilitating late-stage modifications in drug development.