DMAPO/Boc2O-Mediated One-Pot Direct N-Acylation of Less Nucleophilic N-Heterocycles with Carboxylic Acids

In contrast to the considerable progress in the development of methodologies for amide bond formation in amines, the development of direct N-acylation of less nucleophilic N-heterocycles and amides with carboxylic acids is still challenging. In this report, we describe the direct N-acylation of less nucleophilic heterocycles and amides with carboxylic acids promoted by the 4-(N,N-dimethylamino)pyridine N-oxide (DMAPO)/di-tert-butyl dicarbonate (Boc(2)O) system. The new one-pot method, which does not involve pre-activation of substrates, enables the direct N-acylation of a wide variety of nitrogen nucleophiles such as indole, carbazole, pyrrole, pyrazole, lactam, oxazolidinone, and anilide with carboxylic acids in high yield. The new method also exhibits excellent functional group tolerance and broad substrate scope. As the present method is practical, operationally simple, and scalable, it should find wide applications in both academic and industrial laboratories.

Automated summary

This report presents a practical and operationally simple method for the direct N-acylation of less nucleophilic heterocycles and amides with carboxylic acids. The method utilizes the DMAPO/Boc(2)O system and does not require pre-activation of substrates. It demonstrates high yield, excellent functional group tolerance, and broad substrate scope, making it suitable for both academic and industrial laboratories.