INC/CNRS scientific news: breaking the carbon-hydrogen bond is child’s play

The synthesis of organosilanes by breaking carbon-hydrogen bonds is a cost-effective way of introducing silicon into an organic molecule. This difficult operation has been revisited by scientists who are proposing a radically new synthesis route, both rapid and virtuous, for these compounds whose properties have applications in medicinal chemistry and materials science.

Silylation of benzylic C-H bonds with silylated diazenes (tBu-N=N-Si) catalysed by potassium salts. The organometallic intermediates involved in the reaction mechanism are also shown. © Clément Chauvier

Located in the same period of the periodic table as carbon, silicon shares a number of properties with this pillar of organic chemistry, while offering the possibility of exploring new chemical spaces when it is introduced into the structure of organic molecules. The resulting organosilanes have numerous applications in materials science and medicinal chemistry, where they are used, for example, to modulate the pharmacokinetic properties of an active ingredient.

To obtain these compounds, one possible synthesis route involves breaking a carbon-hydrogen bond to insert the silicon atom into the backbone of the organic molecule, which will give it its new properties. Until now, this has been a complex operation, given the strength and ubiquity of C-H bonds, which, in order to be broken, require fairly general processes using catalysts based on noble metals.

Scientists at the Institute of Molecular Chemistry (CNRS/Sorbonne University) are proposing a radically new synthesis method for introducing silicon into a benzyl position, a carbon unit found in a large number of organic molecules. The use of a tert-butyl-silyldiazene (tBu-N=N-SiR3) combined with an abundant and inexpensive potassium-based catalyst enables the silylation of carbon-hydrogen bonds in toluene derivatives. This approach, which combines economy of atoms and mild conditions (ambient temperature, short reaction time), also makes it possible to do without the noble metals traditionally used as catalysts in this type of reaction, while limiting the production of waste to nitrogen (N2) and isobutane.

In addition, theoretical studies using molecular modelling calculations suggest that highly reactive potassium species are involved in the silylation reaction mechanism. In particular, tert-butylpotassium, an analogue in terms of reactivity to tert-butyllithium, which is well known to chemists for its dangerousness, is proposed as a key intermediate to explain the catalytic activity.

This new synthesis methodology, described in the journal Angewandte Chemie, offers a faster and more virtuous route to benzylic silanes.

Reference

Baptiste Neil, Lamine Saadi, Louis Fensterbank & Clément Chauvier
Organopotassium-Catalyzed Silylation of Benzylic C(sp3)‑H Bonds
Angew. Chem. Int. Ed. 2023

https://doi.org/10.1002/anie.202306115

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