Mechanistic Insight into Pd(II)-Catalyzed Late-Stage Nondirected C(sp)-H Cyanation of Toluene Using the Dual Ligands MPAA and Quinoxaline: A Density Functional Theory Investigation.

Density functional theory (DFT) calculations were performed to investigate the mechanism of Pd(II)-catalyzed late-stage nondirected C(sp)-H cyanation of toluene. We confirmed the resting state and catalytic active species of this stoichiometric reaction, and we calculated the full catalytic cycle to obtain a favorable reaction pathway. The DFT calculation results indicate that the morphology of the active species is essential for the observed concerted metalation/deprotonation step. Although C-H activation is reversible in principle, it is the regioselectivity- or product-determining step. Our calculation results show that the regioselectivity is not only influenced by the electron effects but also by the potential steric repulsion interactions between the substrates and the specific geometry of the catalyst. Interestingly, the transmetalation process involves the largest overall change in free energy; thus, transmetalation is defined as the rate-determining step and turnover-determining step.