Direct C–H silylation of arenes is a fundamentally important tool to access highly valuable organosilicon compounds, versatile building blocks in organic synthesis, drug discovery and materials science. To date this task has mainly been achieved via precious transition-metal catalysts that can promote C–H bond activation, though reports in main group chemistry have shown some limited potential of alkali-metal species to mediate these processes.^[1]

Breaking new ground, here we report a new versatile and efficient approach, using the highly encumbered yet strongly basic sodium amide NaTMP (TMP = 2,2,6,6-tetramethylpiperidide) to achieve selective C–H silylation of an array of arenes and heteroarenes with surprisingly excellent regioselective control. This method relies on the prolific ability of NaTMP to promote metalation of aromatic molecules, providing a mild strategy based on the extraordinary reactivity of sodium organometallics.^[2] By pairing this powerful base with bulky electrophilic chlorosilanes, in addition to mono-silylation reactions we can also promote unprecedented regioselective multi-silylation of non-activated arenes such as naphthalene or pyrene. These studies evidence the superior performance of the sodium amide in comparison with other existing metalating reagents. By combining reactivity studies with the trapping of key reaction intermediates, DFT analysis, and NMR reaction monitoring studies, we have gained mechanistic insight into this transformation, where steric and coordination effects possess a key role and reveal the close interplay between sodium and the silicon electrophile required to promote regioselective C–Si bond formation.

[1] (a) Y. Nakao, T. Hiyama, Chem. Soc. Rev. 2011, 40, 4893-4901. (b) C. Cheng, J. F. Hartwig, Chem. Rev. 2015, 115, 8946-8975. (c) A. A. Toutov, W. B. Liu, K. N. Betz, A. Fedorov, B. M. Stoltz, R. H. Grubbs, Nature 2015, 518, 80-84; (d) B. Neil, L. Saadi, L. Fensterbank, C. Chauvier, Angew. Chem. Int. Ed. 2023, 62, e202306115.
[2] (a) L. J. Bole, A. Tortajada, E. Hevia, Angew. Chem. Int. Ed. 2022, 61, e202204262; (b) A. Tortajada, E. Hevia, J. Am. Chem. Soc. 2022, 144, 20237-20242; (c) A. Tortajada, G. L. Righetti, A. McGinley, M. Mu, M. García-Melchor, E. Hevia, Angew. Chem. Int. Ed. 2024, 63, e202407262.