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.
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Data availability
The X-ray crystallographic data for compounds 10c and [Ir]-TolNH2 have been deposited in the Cambridge Crystallographic Data Centre with CCDC nos. 1952123 and 1956819, respectively, and can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/getstructures. All other data supporting the findings of this study are available within the Article and its Supplementary Information.
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Acknowledgements
G.C. acknowledges financial support from grants NSFC-21725204, NSFC-21672105, NSFC-21421062, NSFC-21901127 and NCC2020FH02, the China Postdoctoral Science Foundation (2018M640225, 2019T120179) and Laviana Pharma for the experimental part of this work. S.C. thanks the Institute for Basic Science (IBS-R010-D1) in the Republic of Korea for financial support.
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H.W. formulated the initial ideas for this work, carried out most of the reaction optimization and structural determination of products studies, and prepared the Supplementary Information. F.S. helped with the development of reaction conditions and expansion of substrate scope. S.Z., Z.B. and D.C. helped with expanding the substrate scope. H.J. and H.W. conducted the computational studies and prepared part of the manuscript and Supplementary Information. S.C. supervised the computational studies and edited the manuscript. G.H. supervised experimental studies. G.C. supervised the project, coordinated with S.C. on computational studies, and prepared most of the manuscript.
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Supplementary Information
Supplementary Figs. 1–25 and Tables 1–19. Detailed synthetic procedures, compound characterization, NMR spectra, X-ray crystallographic data and computational details.
Supplementary Data 1
The single point energy output files.
Supplementary Data 1
Crystallographic data for compound 10c. CCDC reference 1952123.
Supplementary Data 2
Crystallographic data for compound [Ir]-TolNH2. CCDC reference 1956819.
Supplementary Data 1
Structure factors file for compound [Ir]-TolNH2. CCDC reference 1956819.
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Wang, H., Jung, H., Song, F. et al. Nitrene-mediated intermolecular N–N coupling for efficient synthesis of hydrazides. Nat. Chem. 13, 378–385 (2021). https://doi.org/10.1038/s41557-021-00650-0
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DOI: https://doi.org/10.1038/s41557-021-00650-0
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