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

• Published in: Polyhedron Vol. 193; p. 114869
• Main Authors: Rajalakshmi, C., Jibin, S.S., Sulay, Rehin, Asha, Sujatha, Ipe Thomas, Vibin, Anilkumar, Gopinathan
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-01-2021
• Subjects: Copper-catalyzed; Cross-coupling; DFT; Sonogashira coupling reaction; Sonogashira coupling reaction; Copper-catalyzed; DFT; Cross-coupling
• ISSN: 0277-5387
• DOI: 10.1016/j.poly.2020.114869

Computational investigation based on Density Functional Theory (DFT) method confirms that the active catalytic species [Cu (L) (phenyl acetylene)] complex, on reaction with aryl halide, undergoes a concerted oxidative addition-reductive elimination process resulting in the formation of a Csp2-Csp bond in the product species, proceeding through a single transition state.
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•First insight into mechanism of copper catalyzed Sonogashira coupling using trans-1,2 diamino cyclohexane ligand.•Reaction mechanism of aryl iodides and substituted aryl iodides with phenylacetylene.•A concerted oxidative addition– reductive elimination mechanism involving a single transition state.•Employed the Density Functional Theory (DFT) using B3LYP functional to study mechanism.•Substrates with electron withdrawing groups reduces the activation energy of reaction by lowering the energy of LUMO.
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.