Copper-Catalyzed C─N Cross-Coupling of Benzohydrazides with Boronic Acids for N-Aryl Amide Synthesis

Abstract

An operationally simple and efficient protocol for the synthesis of N-aryl amides has been developed, based on the copper-catalyzed coupling of benzohydrazides with boronic acids. The transformation relies on the unique in situ activation of the benzohydrazide precursors using a telescoped mixture of tert-butyl nitrite (TBN) and trimethylsilyl chloride (TMSCl). The subsequent cross-coupling process is efficiently promoted by copper(I) chloride, potassium tert-butoxide, and cesium fluoride (CsF) under open-air, ambient-temperature conditions. Furthermore, this one-pot protocol enables rapid access to a broad range of 27 examples of N-aryl amide derivatives, delivering moderate to excellent yields ranging from 40% to 88% under mild conditions with excellent functional group tolerance. The operational simplicity, ambient open-air conditions, demonstrated synthetic utility, and gram-scale applicability underscore the practical value of this protocol.