Heteroaryl amides are ubiquitous motifs in bioactive molecules, yet their efficient synthesis remains challenging due to the high oxidation potential and low nucleophilicity of heteroaryl amines. Herein, we report a redox-mediator-controlled electrochemical strategy for the decarboxylative amidation of α-ketoacids with heteroaryl amines. In this dual-oxidation approach, mediated by ferrocene, both the α-ketoacid and the amine undergo simultaneous single-electron oxidation, generating an acyl radical and a nitrogen-centered radical that cross-couple to afford the desired amides. The method operates under mild conditions, requires no external oxidants, exhibits broad substrate scope, and is readily applicable on a gram scale.
Sa et al. (Mon,) studied this question.