Theoretical Study on the Mechanism of Cobalt-Catalyzed C–O Silylation and Stannylation

[Image: see text] Organosilicon and organotin compounds have been widely used in many fields, such as organic synthesis, materials science, and biochemistry, because of their unique physical and electronic properties. Recently, two novel compounds containing C–Si or C–Sn bonds have been synthesized. These compounds can be used for late modification of drug-like molecules such as probenecid, duloxetine, and fluoxetine derivatives. However, the detailed reaction mechanisms and the influencing factors that determine selectivity are still unclear. Moreover, several questions remain that are valuable to investigate further, such as (1) the influence of the solvent and the lithium salt on the reaction of the Si/Sn–Zn reagent, (2) the stereoselective functionalization of C–O bonds, and (3) the differences between silylation and stannylation. In the current study, we have explored the above issues with density functional theory and have found that stereoselectivity was most likely caused by the oxidative addition of cobalt to the C–O bond of alkenyl acetate with chelation assistance and that transmetalation was most likely the rate-determining step. For Sn–Zn reagents, the transmetalation was achieved by anion and cation pairs, whereas for Si–Zn reagents, the process was facilitated by Co–Zn complexes.