Exploiting Carboxylate Effects to Enhance Cp*Co III -Catalyzed C–H Functionalization

Carboxylates are ubiquitous additives in Cp*Co III -catalyzed C–H functionalization, yet their influence on catalyst speciation and catalytic performance remains poorly understood. Herein, we demonstrate that carboxylate choice can markedly improve reaction efficiency, particularly for substrates bearing weakly coordinating directing groups. Combining high-throughput experimentation (HTE) and reaction optimization, we identified mesitoic acid (MesCO 2 H) as an effective additive for hydrogen isotope exchange (HIE), outperforming conventional carboxylates. We then examined the influence of mesitoate and acetate on Cp*Co III speciation, isolating the corresponding dinuclear complexes. Catalytic studies in HIE revealed that both dimers are catalytically competent, but their activity depends on carboxylate identity and substrate coordination ability, with the mesitoate derivative exhibiting higher activity toward weakly coordinating substrates. We also report the first crystal structure of a direct analogue of the mononuclear κ 2 -carboxylate Cp*Co III species proposed as a putative intermediate prior to C–H activation. The isolated mesitoate-bridged dimer enabled C–H deuteration of pharmaceuticals and agrochemicals and proved effective beyond HIE in three distinct C–H functionalizations. Together, these findings highlight that carboxylate selection can play a decisive role in fine-tuning Cp*Co III catalysis, offering new opportunities for rational reaction optimization. KEYWORDS: Cp*Co III catalysis; C–H activation; catalyst speciation; carboxylates