Mechanochemical Solvent-Free Catalytic C-H Methylation

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.

Automated summary

This new mechanochemical method enables highly regioselective C-H methylation of (hetero)arenes, showing excellent functional-group compatibility and shorter reaction times, and can be used for the synthesis of biologically active compounds.