Mechanistic Insights into a Palladium-Catalyzed Quaternary Carbon-Editing Strategy: A DFT Study

Direct editing of quaternary carbon remains highly challenging. In this study, we computationally investigated a palladium-catalyzed quaternary carbon-editing strategy using density functional theory (DFT) to elucidate its principal characteristics and address key mechanistic issues. A quaternary carbon-editing mechanism driven by sequential Pd migration was established. The results indicate that the total free energy barrier for the transformation is 29.5 kcal mol^-1, which is reasonable under the studied reaction conditions, with 1,3-Pd^IV migration identified as the rate-determining step. Distortion-interaction (D/I) analysis revealed that smaller distortion energy is responsible for the selective palladation. These calculations confirm that 1,3-Pd^IV migration is kinetically more favorable than 1,3-Pd^II migration. Selectfluor can effectively lower the barrier to 1,3-Pd^IV migration, thereby facilitating the conversion. Furthermore, the calculations indicate that the amide bond in the starting reactant (1) plays a critical role in this strategy, particularly in selective palladation and 1,3-Pd migration. Notably, we discovered a novel mechanism involving 1,2-methyl/Pd^IV dyotropic rearrangement and β-hydride elimination. This process exhibits a significantly lower free energy barrier, with methyl migration and HF elimination occurring simultaneously to form a C═C double bond. Thus, these findings enhance the understanding of quaternary carbon-editing strategies and can potentially provide theoretical support for future research.