Aryl-copper(III)-acetylides as key intermediates in C_sp2-C _sp model couplings under mild conditions

The mechanism of copper-mediated Sonogashira couplings (so-called Stephens-Castro and Miura couplings) is not well understood and lacks clear comprehension. In this work, the reactivity of a well-defined aryl-Cu ^III species (1 ClO 4) with p-R-phenylacetylenes (R=NO₂, CF₃, H) is reported and it is found that facile reductive elimination from a putative aryl-Cu^III-acetylide species occurs at room temperature to afford the C_aryl - C_sp coupling species (I_R), which in turn undergo an intramolecular reorganisation to afford final heterocyclic products containing 2H-isoindole (P_NO2, P_CF3, P_Ha) or 1,2-dihydroisoquinoline (P_Hb) substructures. Density Functional Theory (DFT) studies support the postulated reductive elimination pathway that leads to the formation of C _sp2-C_sp bonds and provide the clue to understand the divergent intramolecular reorganisation when p-H-phenylacetylene is used. Mechanistic insights and the very mild experimental conditions to effect C _aryl-C_sp coupling in these model systems provide important insights for developing milder copper-catalysed C_aryl - C _sp coupling reactions with standard substrates in the future.