Copper-Carbon Homolysis Competes with Reductive Elimination in Well-Defined Copper(III) Complexes

Despite the recent advancements of Cu catalysis for the cross-coupling of alkyl electrophiles and the frequently proposed involvement of alkyl-Cu(III) complexes in such reactions, little is known about the reactivity of these high-valent complexes. Specifically, although the reversible interconversion between an alkyl-Cu^III complex and an alkyl radical/Cu^II pair has been frequently proposed in Cu catalysis, direct observation of such steps in well-defined Cu^III complexes remains elusive. In this study, we report the synthesis and investigation of alkyl-Cu^III complexes, which exclusively undergo a Cu-C homolysis pathway to generate alkyl radicals and Cu^II species. Kinetic studies suggest a bond dissociation energy of 28.6 kcal/mol for the Cu^III-C bonds. Moreover, these four-coordinate complexes could be converted to a solvated alkyl-Cu^III-(CF₃)₂, which undergoes highly efficient C-CF₃ bond-forming reductive elimination even at low temperatures (-4 °C). These results provide strong support for the reversible recombination of alkyl radicals with Cu^II to form alkyl-Cu^III species, an elusive step that has been proposed in Cu-catalyzed mechanisms. Furthermore, our work has demonstrated that the reactivity of Cu^III complexes could be significantly influenced by subtle changes in the coordination environment. Lastly, the observation of the highly reactive neutral alkyl-Cu^III-(CF₃)₂ species (or with weakly bound solvent molecules) suggests they might be the true intermediates in many Cu-catalyzed trifluoromethylation reactions.