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Photocatalytic site-selective radical C(sp3)–H aminoalkylation, alkylation and arylation of silanes

Nature Synthesis volume 4, pages 188–195 (2025)Cite this article

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Abstract

Organosilicon compounds are of great value in chemistry and material science. However, site-selective C–H bond functionalization of simple silanes to prepare more complex organosilicon compounds is challenging because of the presence of multiple C–H bonds in the same molecule. Here we report a broadly applicable photocatalytic site-selective radical functionalization of organosilicon compounds enabled by the β-silicon effect, wherein a silyl group selectively activates β-C(sp3)–H bonds, leading to lower bond dissociation energy than that of α-C(sp3)–H bonds and γ-C(sp3)–H bonds. Various β-C(sp3)–H bond aminoalkylation, alkylation and arylation reactions have been achieved and applied in complex molecule synthesis.

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Fig. 1: Background and our strategy of selective β-C(sp3)–H functionalization of silanes.
Fig. 2: β-C(sp3)–H alkylation of silanes with imines and electron-deficient alkenes.
Fig. 3: β-C(sp3)–H alkylation and arylation of silanes.
Fig. 4: Late-stage functionalization, intermolecular competition experiments, downstream transformations and the importance of silicon for high site selectivity.
Fig. 5: Proposed mechanism.

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Data availability

All data are available in the main text or Supplementary Information. Crystallographic data for the structure reported in this Article have been deposited at the Cambridge Crystallographic Data Centre under deposition no. CCDC 2257454 (58). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

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Acknowledgements

We are grateful to National Key R&D Program of China (2022YFA1506100, X.S.), National Natural Science Foundation of China (22471201, X.S.; 21901191, X.S.) and Fundamental Research Funds for the Central Universities (2042023kf0202, X.S.) for financial support. We thank T. Ritter (Max-Planck-Institut für Kohlenforschung) for helpful discussions. We thank R. Zhang from Core Facility of Wuhan University for the assistance with X-ray structure analysis. The theoretical calculations were performed on the supercomputing system in the Supercomputing Center of Wuhan University.

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Authors and Affiliations

  1. The Institute for Advanced Studies, Engineering Research Center of Organosilicon Compounds and Materials, Ministry of Education, Wuhan University, Wuhan, P. R. China

    Xingyi He, Yizhi Zhang, Shanshan Liu, Weilu Zhang, Zhening Liu, Yunlong Zhao & Xiao Shen

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  1. Xingyi He
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Contributions

X.S. conceived the idea, guided the project and wrote the paper with revisions by all the other authors; X.H. developed the catalytic methods and performed the mechanistic studies and synthetic applications. X.H., W.Z., Z.L. and Y. Zhao prepared the substrates and studied the scope. Y. Zhang performed the calculations of the BDEs. S.L. co-guided the project and analysed the spectra data. All the authors were involved in the discussion and analysis of the data.

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Correspondence to Xiao Shen.

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Competing interests

X.S., S.L. and X.H. may benefit from a patent based on the method disclosed in this paper. The other authors declare no competing interests.

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Peer review information

Nature Synthesis thanks Mark McLaughlin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Supplementary information

Supplementary Information

Experimental Details, Discussion, Sections 1–10, Figs. 1–5 and Tables 1–6.

Supplementary Data 1

Crystallographic data for compound 58, CCDC 2257454.

Supplementary Data 2

Structure factors for compound 58, CCDC 2257454.

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He, X., Zhang, Y., Liu, S. et al. Photocatalytic site-selective radical C(sp3)–H aminoalkylation, alkylation and arylation of silanes. Nat. Synth 4, 188–195 (2025). https://doi.org/10.1038/s44160-024-00664-9

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