Role of Silver Salts in Palladium-Catalyzed Arene and Heteroarene C-H Functionalization Reactions

Silver carboxylate salts are widely used as additives in palladium-catalyzed C-H functionalization reactions. However, the role of these silver additives is often not fully understood. This paper describes an investigation of the role of AgOPiv in the stoichiometric activation of C6F5H at a well-defined Pd-II complex as well as in the Pd-II-catalyzed oxidative dimerization of 2-alkylthiophenes. Both in situ NMR spectroscopy and H/D exchange studies of the reactions of C6F5H implicate a role for AgOPiv in the C-H cleavage event, generating Ag-C6F5 as an intermediate. The catalytic studies show similar trends despite the different conditions and substrates, suggesting that AgOPiv promotes a similar metalation of the thiophene in the catalytic transformations. This proposal is supported by DFT calculations, which show energetically feasible pathways for concerted metalation-deprotonation of both 2-methylthiophene and pentafluorobenzene at [Ag(OPiv)](2). These studies suggest that initial metalation of C-H substrates at Ag-I carboxylates should be considered as a plausible pathway in C-H functionalization reactions involving mixtures of Ag and Pd salts.