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.