Rapid and scalable ruthenium catalyzed meta-C-H alkylation enabled by resonant acoustic mixing

Synthetic chemistry approaches for direct C-H bond alkylation offers a promising alternative to traditional functional-group-centered strategies which often involve multi-step procedures and may suffer from a variety of challenges including scalability. Here, we introduce resonant mixing as an efficient method for meta-C-H alkylation of arenes using a Ru-catalyst, avoiding the need for bulk solvents, external temperature, or light. The described methodology is highly rapid, enabling multigram-scale synthesis of meta-alkylation products within a short reaction time and achieving a very high turnover frequency. The reaction operates via a radical mechanism and is characterized by its mild reaction conditions, substrate compatibility, and exceptional meta-selectivity, all while significantly reducing reaction times.