Mechanistic Insights into Rh-Catalyzed Asymmetric Synthesis of Silicon-Stereogenic Silazanes: The Origin of Enantioselectivity

The catalytic asymmetric synthesis of silazanes is always a challenging task. Here, a highly enantioselective synthesis of silicon-stereogenic silazanes was investigated to elucidate the protocol’s principal features and to clarify the origin of the enantioselectivity by using DFT calculations. The computational results indicate that the total free energy barrier for the conversion is 19.9 kcal/mol, which is reasonable given the current reaction conditions. Consistent with the experimental findings, the calculations indicate that σ-bond metathesis (N–H bond cleavage) is the rate-determining step for this transformation. Both pathways 1 and 2 toward S- or R-configuration products were investigated computationally. We found that the main enantiomer product of this transformation is determined by the kinetically more favorable main reaction pathway 1. Calculations indicate that the loss of one or the other H on the dihydrosilane will lock the product chirality; therefore, the oxidative addition is the enantioselectivity-determining step. Non-covalent interaction (NCI) analysis confirms that a difference in steric hindrance is responsible for the enantioselectivity of the protocol. Additionally, calculations confirm that the electron-donating group on aniline appropriately lowers the free energy barrier relative to the electron-withdrawing group (ΔG = 15.5 vs 21.6 kcal/mol), thereby accelerating the conversion.