ABSTRACT Efficient amide bond formation is pivotal in drug development, yet traditional methods often rely on pre‐activated substrates or toxic reagents. We present a copper‐catalyzed, CS 2 ‐mediated direct amidation enabling carboxylic acids and anilines to couple under mild, aerobic conditions without pre‐activation. The strategy achieves late‐stage modification of pharmaceuticals, amino acids, and peptides, showcasing broad substrate tolerance and functional group compatibility. Mechanistic insights identify thiourea‐derived carbodiimide intermediates via oxygen‐dependent desulfurization.
Zhong et al. (Thu,) studied this question.