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Deaminative Giese-type reaction

Nature Chemistry volume 17, pages 1556–1564 (2025)Cite this article

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Abstract

Primary aliphatic amines are essential components in numerous functional molecules and rank among the most readily available commercial building blocks. Although commonly utilized as nitrogen nucleophiles, their application as alkyl sources for constructing (sp3)C–C(sp3) bonds remains a notable challenge. Here we present an approach integrating nitrogen-atom deletion into the aza-Michael reaction, thereby redirecting the classical pathway from (sp3)C–N bond formation to (sp3)C–C(sp3) bond construction. Leveraging commercially available O-diphenylphosphinylhydroxylamine as an efficient nitrogen-deletion reagent, this method enables a wide variety of primary aliphatic amines to serve as alkyl sources in couplings with structurally diverse electron-deficient olefins. This Giese-type reaction proceeds under mild conditions, achieves completion within 10 min and exhibits broad functional-group compatibility. By bridging two foundational transformations—the aza-Michael reaction and the Giese-type reaction—this approach interlinks their product spaces through a unified precursor library, substantially enhancing synthetic utility.

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Fig. 1: Background and our strategy to access a direct deaminative Giese-type reaction.
Fig. 2: Late-stage modification and synthesis of bioactive molecules.
Fig. 3: Multiple functionalization using a nitrogen atom as a traceless directing group.
Fig. 4: Mechanistic studies.

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The data supporting the findings of this study are available within the Article and its Supplementary Information.

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Acknowledgements

Financial support for this work was provided by the National Natural Science Foundation of China (22071100, 22271148) and the Natural Science Foundation of Jiangsu Province (BK20231400).

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Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China

    Panpan Ma, Zhangkai Cui & Hongjian Lu

  2. The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Normal University, Wuhu, China

    Hongjian Lu

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  1. Panpan Ma
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  2. Zhangkai Cui
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Contributions

P.M. and H.L. designed the experiments. P.M. and Z.C. performed the experiments and analysed the data. All authors participated in writing the paper. H.L. conceived and supervised the project.

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Correspondence to Hongjian Lu.

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Supplementary Figs. 1 and 2, Experimental procedures and NMR spectra.

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Ma, P., Cui, Z. & Lu, H. Deaminative Giese-type reaction. Nat. Chem. 17, 1556–1564 (2025). https://doi.org/10.1038/s41557-025-01888-8

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