An aerobic copper-catalyzed multi-component reaction strategy for N′,N′-diaryl acylhydrazine synthesis: reactions and mechanism

Abstract

A sequential multi-component reaction of aldehydes and aryl hydrazines for the synthesis of N′,N′-diaryl acylhydrazines with high regioselectivity has been achieved via an aerobic copper-catalyzed process. This mild, operationally simple method enables the transformation of commercially available aldehydes, along with aryl hydrazines, into the corresponding N′,N′-diaryl acylhydrazines with high regioselectivity and in moderate to good yields. This transformation employs aryl hydrazine as a dual synthon – a hydrazine and an aryl synthon. The value of this efficient synthetic protocol has been demonstrated through a gram-scale experiment and late-stage modification of bioactive natural products and drug molecules. Mechanistic investigations support the generation of an acyl diazene intermediate and an aryl radical species, along with the dual role of air as the sole oxidant and the source of the oxygen functionality in this aerobic C–N bond coupling reaction.