Mechanochemical Solvent-Free Catalytic C-H Methylation

Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6660-6666. doi: 10.1002/anie.202010202. Epub 2020 Dec 17.

Abstract

The mechanochemical, solvent-free, highly regioselective, rhodium-catalyzed C-H methylation of (hetero)arenes is reported. The reaction shows excellent functional-group compatibility and is demonstrated to work for the late-stage C-H methylation of biologically active compounds. The method requires no external heating and benefits from considerably shorter reaction times than previous solution-based C-H methylation protocols. Additionally, the mechanochemical approach is shown to enable the efficient synthesis of organometallic complexes that are difficult to generate conventionally.

Keywords: C−H functionalization; arenes; mechanochemistry; organometallics; rhodium.