Mechanochemical Functionalization of Heterocycles by C–H Activation: An Update

The mechanochemical C-H activation of heterocycles presents a sustainable, solvent-free alternative to the traditional solution-phase synthesis. Heterocycles are fundamental molecular scaffolds in medicinal chemistry and drug discovery. This review highlights recent advances in mechanochemical methods for metal-catalyzed and metal-free C-H functionalization/derivatization, including arylation, alkenylation, acylation, borylation, trifluoromethylation, etc., applied across various heterocyclic compounds. Emphasizing green aspects, this synopsis provides a comprehensive overview of mechanochemical innovations, their unique features and advantages, transformative potential for ecofriendly synthesis, and future prospects of sustainability.