Enabling Room-Temperature Copper Cross-Coupling Reactions of Anilines with Aryl Bromides

Biaryl amines are essential structural motifs prevalent in agrochemicals, pharmaceuticals, and materials. Herein, we present a novel copper-catalyzed method for aniline cross-couplings promoted by a 6-hydroxy picolinhydrazide ligand. The method achieves room-temperature reactivity with aryl bromides, enabled by a methanol/ethanol solvent mixture and a mild, functional group-compatible base, with catalyst loadings as low as 0.5 mol%. The use of industrially preferred bases and solvents, as well as the high catalytic activity, offers a significant advancement in the practicality and scalability of industrial processes. Furthermore, the approach extends to the cross-coupling of aryl chlorides under elevated temperatures and demonstrates compatibility with additional nucleophile classes.