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.
- C-H functionalization
- late-stage functionalization