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 (Boc2O) 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.
This report describes a general method for the one‐pot direct N‐acylation of N‐heterocycles using our previously developed 4‐(N,N‐dimethylamino)pyridine N‐oxide (DMAPO)/di‐tert‐butyl dicarbonate (Boc2O) system. This system enables one‐pot N‐acylation reactions to provide bulky N‐acyl heterocycles starting from a wide variety of less nucleophilic N‐heterocycles and sterically hindered α‐fully substituted carboxylic acids in high yields. Moreover, this one‐pot method does not involve pre‐activation of substrates. The protocol has been successfully extended to one‐pot N‐acylation of 7‐azaindoles.
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