Elementary Steps of Silver- and Gold-Mediated Trifluoromethylation Reactions

Due to the importance of the trifluoromethyl group in medicinal chemistry, trifluoromethylation reactions are in high demand. Most of the reported trifluoromethylation protocols rely on copper complexes, whose mechanistic role in these transformations has been analyzed extensively. First evidence also points to the potential of silver and gold complexes for enabling trifluoromethylation reactions, but a more detailed mechanistic understanding of these processes is still lacking. Here, we use electrospray-ionization mass spectrometry to study the formation of [Ag(R)(CF₃)₃]⁻ and [Au(R)(CF₃)₃]⁻ (R = Me, Et, ⁿBu, ^sBu, allyl, aryl) in solution and characterize their unimolecular reactivity by gas-phase fragmentation experiments and quantum chemical calculations. The argentate complexes undergo both concerted reductive eliminations of RCF₃ and 2-fold radical losses of R^• and CF₃^•. Like in the case of the analogous cuprate complexes, the branching ratio between the two competing fragmentation channels is controlled by the stability of the R^• radicals. In contrast, the calculated barriers of the corresponding fragmentation reactions of the aurates are much higher, for which reason these complexes dissociate by alternative pathways and do not afford the RCF₃ products.