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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.

References

  1. Zhang, P., Zhang, D., Dong, J., Chen, G. & Li, J. Direct synthesis of methylchlorosilanes: catalysts, mechanisms, reaction conditions, and reactor designs. Org. Process Res. Dev. 26, 2270–2280 (2022).

    Article  CAS  Google Scholar 

  2. Zhang, Y., Li, J., Liu, H., Zhong, Z. & Su, F. Recent advances in Rochow-Müller process research: driving to molecular catalysis and to a more sustainable silicone industry. ChemCatChem 11, 2757–2779 (2019).

    Article  CAS  Google Scholar 

  3. Seyferth, D. Dimethyldichlorosilane and the direct synthesis of methylchlorosilanes. The key to the silicones industry. Organometallics 20, 4978–4992 (2001).

    Article  CAS  Google Scholar 

  4. Clarke, M. P. The direct synthesis of methylchlorosilanes. J. Organomet. Chem. 376, 165–222 (1989).

    Article  CAS  Google Scholar 

  5. Arkles, B. in Handbook of Grignard Reagents (eds Silverman, G. S. & Rakita, P. E.) 667–675 (Dekker, 1996).

  6. He, T., Klare, H. F. T. & Oestreich, M. Silylium-ion regeneration by protodesilylation enables Friedel–Crafts alkylation with less isomerization and no defunctionalization. ACS Catal. 11, 12186–12193 (2021).

    Article  CAS  Google Scholar 

  7. Wu, Q. et al. Cleavage of unactivated Si–C(sp3) bonds with Reed’s carborane acids: formation of known and unknown silylium ions. Angew. Chem. Int. Ed. 57, 9176–9179 (2018).

    Article  CAS  Google Scholar 

  8. Fleming, I., Henning, R. & Plaut, H. The phenyldimethylsilyl group as a masked form of the hydroxy group. J. Chem. Soc. Chem. Commun. 29–31 (1984).

  9. Jones, G. R. & Landais, Y. The oxidation of the carbon-silicon bond. Tetrahedron 52, 7599–7662 (1996).

    Article  CAS  Google Scholar 

  10. Benkeser, R. A. & Muench, W. C. New synthesis of internally substituted alkyl silanes. J. Am. Chem. Soc. 95, 285–286 (1973).

    Article  CAS  Google Scholar 

  11. Watanabe, H., Aoki, M., Sakurai, N., Watanabe, K. & Nagai, Y. Selective synthesis of mono-alkyldichlorosilanes via the reaction of olefins with dichlorosilane catalyzed by group VIII metal phosphine complexes. J. Organomet. Chem. 160, C1–C7 (1978).

    Article  CAS  Google Scholar 

  12. Out, G. J. J., Klok, H. A., Schwegler, L., Frey, H. & Möller, M. Hydrosilylation of 1-alkenes with dichlorosilane. Macromol. Chem. Phys. 196, 185–194 (1995).

    Article  CAS  Google Scholar 

  13. Yuan, W., Smirnov, P. & Oestreich, M. Custom hydrosilane synthesis based on monosilane. Chem 4, 1443–1450 (2018).

    Article  CAS  Google Scholar 

  14. Smirnov, P. & Oestreich, M. Merging platinum-catalyzed alkene hydrosilylation with SiH4 surrogates: salt-free preparation of trihydrosilanes. Organometallics 35, 2433–2434 (2016).

    Article  CAS  Google Scholar 

  15. Fan, X. et al. Stepwise on-demand functionalization of multihydrosilanes enabled by a hydrogen-atom-transfer photocatalyst based on eosin Y. Nat. Chem. 15, 666–676 (2023).

    Article  CAS  PubMed  Google Scholar 

  16. Chan, T. H. & Fleming, I. Electrophilic substitution of organosilicon compounds—applications to organic synthesis. Synthesis 761–786 (1979).

  17. Matsuoka, K. et al. Chemoselective cleavage of Si–C(sp3) bonds in unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). J. Am. Chem. Soc. 143, 103–108 (2021).

    Article  CAS  PubMed  Google Scholar 

  18. Roy, A. & Oestreich, M. At long last: the Me3Si group as a masked alcohol. Angew. Chem. Int. Ed. 60, 4408–4410 (2021).

    Article  CAS  Google Scholar 

  19. Klare, H. F. T. & Oestreich, M. The power of the proton: from superacidic media to superelectrophile catalysis. J. Am. Chem. Soc. 143, 15490–15507 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. Kipping, F. S. Organic derivatives of silicon. Part III. dl-Benzylmethylethylpropylsilicane and experiments on the resolution of its sulphonic derivative. J. Chem. Soc. Trans. 91, 717–747 (1907).

    Article  CAS  Google Scholar 

  21. Sommer, L. H., Marans, N. S., Goldberg, G. M., Rockett, J. & Pioch, R. P. A new reaction in organosilicon chemistry. J. Am. Chem. Soc. 73, 882 (1951).

    Article  CAS  Google Scholar 

  22. Sommer, L. H. et al. Aliphatic organo-functional siloxanes. J. Am. Chem. Soc. 75, 2932–2934 (1953).

    Article  CAS  Google Scholar 

  23. Sommer, L. H., Barie, W. P. & Gould, J. R. Kinetics and mechanism of methyl–silicon cleavage by sulfuric acid. J. Am. Chem. Soc. 75, 3765–3767 (1953).

    Article  CAS  Google Scholar 

  24. Shorr, L. M., Freiser, H. & Speier, J. L. Methyl–silicon cleavage of certain substituted carboxylic acids in sulfuric acid. Kinetics and mechanism. J. Am. Chem. Soc. 77, 547–551 (1955).

    Article  CAS  Google Scholar 

  25. O’Brien, D. H. & Harbordt, C. M. Cleavage of alkylsilanes by strong acids. J. Organomet. Chem. 21, 321–328 (1970).

    Article  Google Scholar 

  26. Olah, G. A., Husain, A., Gupta, B. G. B., Salem, G. F. & Narang, S. C. Synthetic methods and reactions 104. Silylations with in situ generated trimethylsilyl triflate reagent systems. J. Org. Chem. 46, 5212–5214 (1981).

    Article  CAS  Google Scholar 

  27. Finke, U., Moretto, H.-H., Niederprüm, H. & Vorbrüggen, H. Silylester der Perfluoralkansulfonsauren sowie Verfahren zu deren Herstellung. German patent DE2803125A1 (1978).

  28. Demuth, M. & Mikhail, G. A convenient in situ preparation of trimethylsilyl trifluoromethanesulfonate. Synthesis 827 (1982).

  29. Reed, C. A. Myths about the proton. The nature of H+ in condensed media. Acc. Chem. Res. 46, 2567–2575 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Reed, C. A. H+, CH3+, and R3Si+ carborane reagents: when triflates fail. Acc. Chem. Res. 43, 121–128 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Russell, G. A. Catalysis by metal halides. III. The question of the existence of siliconium ions. J. Am. Chem. Soc. 81, 4831–4833 (1959).

    Article  CAS  Google Scholar 

  32. Eaborn, C. Organosilicon compounds. Part I. The formation of alkyliodosilanes. J. Chem. Soc. 2755–2764 (1949).

  33. Russell, G. A. Catalysis by metal halides. I. Mechanism of the disproportionation of ethyltrimethylsilane. J. Am. Chem. Soc. 81, 4815–4825 (1959).

    Article  CAS  Google Scholar 

  34. Sakurai, H., Tominaga, K., Watanabe, T. & Kumada, M. Aluminium chloride-catalyzed reactions of organosilicon compounds II. Facile syntheses of alkylchlorosilanes, -germanes, and -stannanes. Tetrahedron Lett. 7, 5493–5497 (1966).

    Article  Google Scholar 

  35. Haubold, W., Gemmler, A. & Kraatz, U. Tetramethylsilan – ein Methylierungsreagenz für Bortrihalogenide. Z. Naturforsch. 33b, 140–141 (1978).

    Article  CAS  Google Scholar 

  36. Bordeau, M., Djamei, S. M., Calas, R. & Dunogues, J. Nouvelles utilisations du tétraméthylsilane comme agent de méthylation des chlorosilanes; valorisation du méthyltrichlorosilane. J. Organomet. Chem. 288, 131–138 (1985).

    Article  CAS  Google Scholar 

  37. Heyduk, A. F., Labinger, J. A. & Bercaw, J. E. Catalytic alcoholysis of tetramethylsilane via Pt-mediated C–H bond activation. J. Am. Chem. Soc. 125, 6366–6367 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Alyev, I. Y., Rozhkov, I. N. & Knunyants, I. L. Anode chemistry of organosilanes. Oxidative replacement of alkyl group by fluoride ion. Tetrahedron Lett. 17, 2469–2470 (1976).

    Article  Google Scholar 

  39. Schäfer, A. et al. A new synthesis of triarylsilylium ions and their application in dihydrogen activation. Angew. Chem. Int. Ed. 50, 12636–12638 (2011).

    Article  Google Scholar 

  40. Labbow, R., Reiß, F., Schulz, A. & Villinger, A. Synthesis of the first persilylated ammonium ion, [(Me3Si)3NSi(H)Me2]+, by silylium-catalyzed methyl/hydrogen exchange reactions. Organometallics 33, 3223–3226 (2014).

    Article  CAS  Google Scholar 

  41. Omann, L. et al. Thermodynamic versus kinetic control in substituent redistribution reactions of silylium ions steered by the counteranion. Chem. Sci. 9, 5600–5607 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bähr, S. & Oestreich, M. A neutral RuII hydride complex for the regio- and chemoselective reduction of N-silylpyridinium ions. Chem. Eur. J. 24, 5613–5622 (2018).

    Article  PubMed  Google Scholar 

  43. Torigoe, T., Ohmura, T. & Suginome, M. Utilization of a trimethylsilyl group as a synthetic equivalent of a hydroxyl group via chemoselective C(sp3)–H borylation at the methyl group on silicon. J. Org. Chem. 82, 2943–2056 (2017).

    Article  CAS  PubMed  Google Scholar 

  44. Kajita, D. et al. Design and synthesis of silicon-containing fatty acid amide derivatives as novel peroxisome proliferator-activated receptor (PPAR) agonists. Bioorg. Med. Chem. Lett. 25, 3350–3354 (2015).

    Article  CAS  PubMed  Google Scholar 

  45. Lehmann, M., Schulz, A. & Villinger, A. Bissilylated halonium ions: [Me3Si–X–SiMe3][B(C6F5)4] (X=F, Cl, Br, I). Angew. Chem. Int. Ed. 48, 7444–7447 (2009).

    Article  CAS  Google Scholar 

  46. Budanow, A. et al. Two-coordinate gallium ion [tBu3Si-Ga-SitBu3]+ and the halonium ions [tBu3Si-X-SitBu3]+ (X = Br, I): sources of the supersilyl cation [tBu3Si]+. Organometallics 31, 7298–7301 (2012).

    Article  CAS  Google Scholar 

  47. Budanow, A., Bolte, M., Wagner, M. & Lerner, H.-W. The ion-like supersilylium compound tBu3Si–F–Al[OC(CF3)3]3. Eur. J. Inorg. Chem. 2524–2527 (2015).

  48. Merk, A. et al. Intramolecular halo stabilization of silyl cations—silylated halonium- and bis-halo-substituted siliconium borates. Chem. Eur. J. 27, 3496–3503 (2021).

    Article  CAS  PubMed  Google Scholar 

  49. Klare, H. F. T. et al. Silylium ions: from elusive reactive intermediates to potent catalysts. Chem. Rev. 121, 5889–5985 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Allemann, O., Duttwyler, S., Romanato, P., Baldridge, K. K. & Siegel, J. S. Proton-catalyzed, silane-fueled Friedel–Crafts coupling of fluoroarenes. Science 332, 574–577 (2011).

    Article  ADS  CAS  PubMed  Google Scholar 

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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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