Mechanism of Ruthenium-Catalyzed Direct Arylation of C–H Bonds in Aromatic Amides: A Computational Study

Ruthenium-catalyzed arylation of ortho C–H bonds directed by a bidentate 8-aminoquinoline moiety not only is important to construct new biaryl derivates but also merges important research areas. In this study, the density functional theory (DFT) method M11-L was employed to predict the mechanism of this C–H bond arylation reaction. The computational results indicate that the initial step for this reaction is catalyst loading by electrophilic deprotonation to generate a substrate-coordinated Ru­(II) intermediate, which is the key compound in the complete catalytic cycle. The catalytic cycle includes electrophilic deprotonation by carbonate, oxidative addition of bromobenzene, reductive elimination to form a new aryl–aryl bond, proton transfer to release the product, and ligand exchange to regenerate the initial Ru­(II) intermediate. Theoretical calculations suggest that the oxidative addition of bromobenzene is the rate-determining step of the whole catalytic cycle, and the apparent activation free energy is 32.7 kcal/mol. The ligand effect was considered in DFT calculations, and the calculated results agree well with experimental observations.