Mechanistic insights into the synergistic catalysis by Au(I), Ga(III), and counterions in the Nakamura reaction

A computational study based on density functional theory (DFT) establishes the mechanisms for synergistic Au/Ga catalyzed addition of unactivated terminal alkynes to dicarbonyls, the Nakamura reaction. The role played by each of the metal catalysts and the counterion in the reaction has been elucidated. It has been shown that the triazole (TA) ligand could specifically activate the formation of a particular regio-isomer through strong non-covalent interactions. Calculated regioselectivities and activation free energies are in excellent agreement with the experimental results. Observed regioselectivities were rationalized employing a distortion interaction analysis which suggests that the interaction between metal activated reactant fragments in the transition state geometries is a major factor that contributes to the overall barrier height and selectivity. Such enhanced preference for the reaction at the alkyl/aryl substituted carbon of alkynes was strongly influenced by the additional non-covalent interactions exerted by the TA ligand. Excellent agreement between the calculations using a homogeneous gold complex as the catalyst and experimentally observed kinetics and selectivity negates the role of in situ formed gold clusters in the Nakamura reaction.