Theoretical investigation into the mechanism of copper-catalyzed Sonogashira coupling using trans-1,2-diamino cyclohexane ligand

Abstract

The mechanism of copper-catalyzed Sonogashira coupling reaction employing trans-1,2-diamino cyclohexane ligand have been investigated with Density Functional Theory (DFT) method augmented with Conductor-like Polarizable Continuum Model (CPCM) solvation model. The cross-coupling reactions could be accelerated by employing chelating diamine ligands. Thus, we considered trans-1,2-diamino cyclohexane as the ligand for our study. These coupling reactions find its applicability in the synthesis of aryl acetylenes, the precursors for the various benzofuran derivatives which are present in many biologically important compounds. Considering various reaction pathways possible, it was found that diamine ligated copper (I) acetylide was the active state of the catalyst, which on further reaction with aryl halide undergoes a concerted oxidative addition – reductive elimination process giving the cross-coupled product aryl acetylene while regenerating the active catalytic species. Unlike the Pd-catalyzed Sonogashira cross-coupling, there occurs a concerted mechanism owing to the ease of bond formation between Csp2-Csp carbon atoms and instability of a Cu (III) metal center. This shows the mechanism of copper-catalyzed cross-couplings are quite different from that of Pd catalyzed reactions. The latter usually involves individual process involving oxidative addition and reductive elimination. The presences of various functional groups on the substrate molecules have a crucial role in determining the feasibility of the reaction. Henceforth, we have investigated the electronic effects of various functional groups in the substrate molecule on the activation barrier of the cross-coupling reaction.