DFT Study on Mechanism of Ruthenium-catalyzedmetaSulfonation

Abstract

The transition metal catalyzed direct C—H functionalization reaction is an important strategy for selective activa- tion 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 regen- eration. It is found that the ortho C-H activation is the rate-determing step of overall catalytic cycle. At 298.15 K and stan- dard 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 experimen- tal yields reported by Frost et al. All these consistency verify the calculation results provided in this study. Keywords Ru catalysis; meta sulfonation; C—H functionalization; mechanism; density functional theory (DFT)