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Arenium-ion-catalysed halodealkylation of fully alkylated silanes

Nature volume 623, pages 538–543 (2023)Cite this article

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Abstract

‘Organic silicon’ is not found in nature but modern chemistry is hard to imagine without silicon bound to carbon. Although silicon-containing commodity chemicals such as those emerging from the ‘direct process’1,2,3,4 look simple, it is not trivial to selectively prepare aryl-substituted and alkyl-substituted (functionalized) silicon compounds, known as silanes. Chlorosilanes such as Me4−nSiCln (n = 1–3) as well as SiCl4 (n = 4) are common starting points for the synthesis of silicon-containing molecules. Yet these methods often suffer from challenging separation problems5. Conversely, silanes with four alkyl groups are considered synthetic dead ends. Here we introduce an arenium-ion-catalysed halodealkylation that effectively converts Me4Si and related quaternary silanes into a diverse range of functionalized derivatives. The reaction uses an alkyl halide and an arene (co)solvent: the alkyl halide is the halide source that eventually engages in a Friedel–Crafts alkylation with the arene to regenerate the catalyst6, whereas the arenium ion acts as a strong Brønsted acid for the protodealkylation step7. The advantage of the top-down halodealkylation methodology over reported bottom-up procedures is demonstrated, for example, in the synthesis of a silicon drug precursor. Moreover, chemoselective chlorodemethylation of the rather inert Me3Si group attached to an alkyl chain followed by oxidative degradation is shown to be an entry into Tamao–Fleming-type alcohol formation8,9.

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Fig. 1: Substitution reactions at silicon atoms.
Fig. 2: Chemoselective halodealkylation of tetraalkylsilanes.
Fig. 3: Chemoselective chlorodealkylation followed by derivatization with carbon and heteroatom nucleophiles.
Fig. 4: Proposed initiation and catalytic cycle of the arenium-ion-promoted halodealkylation of fully alkylated silanes.

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The authors declare that all other data supporting the findings of this study are available in the Article and its Supplementary Information and are also available from the corresponding author on request.

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Acknowledgements

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2008/1-390540038, UniSysCat). M.O. is indebted to the Einstein Foundation Berlin for an endowed professorship.

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  1. Institut für Chemie, Technische Universität Berlin, Berlin, Germany

    Tao He, Hendrik F. T. Klare & Martin Oestreich

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Contributions

T.H., H.F.T.K. and M.O. conceived the work and designed the experiments. T.H. performed the experiments and analysed the data. T.H., H.F.T.K. and M.O. discussed the results and co-wrote the manuscript.

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Correspondence to Hendrik F. T. Klare or Martin Oestreich.

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Nature thanks Chuan He, Shigeki Matsunaga and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

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Extended Data Table 1 Optimization of the catalytic halodeethylation of tetraethylsilanea
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He, T., Klare, H.F.T. & Oestreich, M. Arenium-ion-catalysed halodealkylation of fully alkylated silanes. Nature 623, 538–543 (2023). https://doi.org/10.1038/s41586-023-06646-9

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