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Energy transfer-enabled unsymmetrical diamination using bifunctional nitrogen-radical precursors

Nature Catalysis volume 5, pages 1120–1130 (2022)Cite this article

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Abstract

Vicinal diamines, especially unsymmetrical ones, are among the most common structural motifs in biologically active molecules, natural products and pharmaceuticals. While the catalytic diamination of carbon–carbon double bonds provides rapid access to diamines, these reactions are often limited to installation of undifferentiated amino functionalities through transition metals or hypervalent iodine reagent catalysis. Herein we disclose a metal-free, photosensitized dearomative unsymmetrical diamination of various electron-rich (hetero)arenes with bifunctional diamination reagents, producing a series of previously inaccessible vicinal diamines with excellent regio- and diastereoselectivity. A class of bifunctional nitrogen-radical precursors was developed to simultaneously generate two N-centred radicals with different reactivity via an energy transfer process. In addition, the protocol was also found suitable for a wide range of alkenes. Notably, the formed vicinal diamines bear two differentiated amino functionalities, and either imine or amide units could readily and orthogonally be converted to unprotected amines, thereby facilitating selective downstream transformations.

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Fig. 1: Development of nitrogen-radical precursors.
Fig. 2: Reaction development.
Fig. 3: Mechanistic investigations.
Fig. 4: Dearomative unsymmetrical diamination of (hetero)arenes.
Fig. 5: Unsymmetrical diamination of alkenes.
Fig. 6: Synthetic applications.

Data availability

Materials and methods, experimental procedures, mechanistic studies, computational studies, sensitivity assessment and nuclear magnetic resonance (NMR) spectra are available in the Supplementary Information. Crystallographic information data files and xyz coordinates of the optimized structures are available as Supplementary files. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre under deposition nos. CCDC 2145161 (21) and 2145162 (66). Copies of crystallographic data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All other data are available from the authors upon reasonable request.

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Acknowledgements

We thank P. Bellotti, X. Yu, X. Zhang (all WWU) and H. Keum (KAIST) for helpful assistance and discussions. Generous financial support provided by the Alexander von Humboldt Foundation (G.T.), Fonds der Chemischen Industrie (R.K., Kekulé Scholarship no. 106151) and Deutsche Forschungsgemeinschaft (no. SFB 858) is gratefully acknowledged.

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Authors and Affiliations

  1. Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Münster, Germany

    Guangying Tan, Mowpriya Das, Roman Kleinmans, Felix Katzenburg, Constantin Daniliuc & Frank Glorius

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  1. Guangying Tan
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  2. Mowpriya Das
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  3. Roman Kleinmans
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Contributions

F.G. and G.T. conceived the project. G.T. and R.K. performed the initial screening experiments. G.T. and M.D. performed synthetic experiments. F.K. conducted computations. C.D. analysed X-ray structures. G.T. and F.G. supervised research and wrote the manuscript with contributions from all authors.

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Correspondence to Frank Glorius.

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Nature Catalysis thanks Wujiong Xia, Fangrui Zhong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–16 and Tables 1–4.

Supplementary Data 1

Crystallographic data for compound 21.

Supplementary Data 2

Crystallographic data for compound 66.

Supplementary Data 3

Cartesian coordinates for all calculated structures.

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Tan, G., Das, M., Kleinmans, R. et al. Energy transfer-enabled unsymmetrical diamination using bifunctional nitrogen-radical precursors. Nat Catal 5, 1120–1130 (2022). https://doi.org/10.1038/s41929-022-00883-3

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