The transition metal catalyzed direct C—H functionalization reaction is an important strategy for selective activation of aromatic C—H bond and its functionalization. In the present study, DFT method (M06//B3LYP) has been used for mechanistic study on the Ruthenium-catalyzed meta-sulfonation of 2-phenylpyridines reported by Frost and co-workers. All calculations involved in this study were performed using Gaussian09 suite of program. The proposed mechanism consists of four main steps: pyridine directed ortho C—H activation, electrophilic substitution, reductive elimination and catalyst regeneration. It is found that the ortho C-H activation is the rate-determing step of overall catalytic cycle. At 298.15 K and standard pressure, the KIE of ortho C—H activation step was calculated for the model reaction. Good agreement has been gained between the calculations (KIE=4.8) and the experimental observed primary isotope effect (KIE=3.0). The regioselectivity determining step of the catalytic cycle is found to be the electrophilic substitution. With the coordination of Ru center to the ortho carbon atom, the electron density distribution on the benzene ring of cycloruthenium intermediate changes accordingly. The charge distribution and the steric hindrance around the Ru center then make the electrophilic substitution occur favorably at the para-position of Ru—C bond (the para-position of directing group) in preference to the chelating-C or the ortho of the chelating group. In one word, regioselectivity was determined by electrophilic substitution, rather than the directed C—H activation. In the process of reaction, K₂CO₃ played an important role in promoting the reaction. K₂CO₃ first participates in the ortho C—H activation, and then it stabilizes the TsCl dissociating intermediates. In the electrophilic substitution step, K₂CO₃ directly engages in the cleavage of C—H bonds. Finally K₂CO₃ takes part in the generation of ortho C—H. As to the solvent effect, we found that the rate determining step changes with the changes of solvent polarity. When the solvent changes from acetonitrile to toluene (or dioxane), the rate determining step would vary from ortho C—H activation to the TsCl dissociation and the reaction activation energy would increase accordingly. This trend is consistent with the experimental yields reported by Frost et al. All these consistency verify the calculation results provided in this study.

Key words: Ru catalysis, meta sulfonation, C—H functionalization, mechanism, density functional theory (DFT)