Direct access to hydrazides and amides from carboxylic acids via acyloxyphosphonium ion

Abstract

Adding an amine moiety to a carbonyl group poses a challenging synthetic task; nevertheless, it is a crucial step in developing numerous bioactive molecules. Here, we report a straightforward and efficient protocol for synthesizing various amides using deoxygenated amidation of abundant carboxylic acids. This modular one-pot method uses feedstock carboxylic acids as acyl surrogates, amines, and sulfonyl hydrazides as coupling reagents. This method is a simple and affordable way to introduce structural diversity. Several biologically relevant skeletons have been easily synthesized under mild conditions. We identified the crucial reaction intermediates, bromophosphonium ion, and acyloxyphosphonium ion, through NMR spectroscopy. We have also used this protocol for the late-stage functionalization of pharmaceuticals and blockbuster drugs.