Nitrene-mediated intermolecular N–N coupling for efficient synthesis of hydrazides

Abstract

N–N linkages are found in many natural compounds and endow fascinating structural and functional properties. In comparison to the myriad methods for the construction of C–N bonds, chemistry for N–N coupling, especially in an intermolecular fashion, remains underdeveloped. Here, we report a nitrene-mediated intermolecular N–N coupling of dioxazolones and arylamines under iridium or iron catalysis. These reactions offer a simple and efficient method for the synthesis of various hydrazides from readily available carboxylic acid and amine precursors. Although the Ir-catalysed conditions usually give higher N–N coupling yield than the Fe-catalysed conditions, the reactions of sterically more demanding dioxazolones derived from α-substituted carboxylic acids work much better under the Fe-catalysed conditions. Mechanistic studies revealed that the nitrogen atom of Ir acyl nitrene intermediates has strong electrophilicity and can undergo nucleophilic attack with arylamines with the assistance of Cl···HN hydrogen bonding to form the N–N bond with high efficiency and chemoselectivity. Although many natural products and drug molecules contain N–N linkages, the chemistry of N–N coupling is somewhat underdeveloped. Now, a nitrene-mediated intermolecular N–N coupling of dioxazolones and arylamines that relies on iridium or iron catalysis has been developed. These reactions offer a simple and efficient method for the synthesis of hydrazides from readily available precursors.

Cite this article

Wang, H., Jung, H., Song, F. et al. Nitrene-mediated intermolecular N–N coupling for efficient synthesis of hydrazides. Nat. Chem. (2021). https://doi.org/10.1038/s41557-021-00650-0

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