Geminal bond participation in the uncatalyzed Mukaiyama aldol reaction

We predicted that uncatalyzed Mukaiyama aldol reactions are under the control of the geminal bond participation. At the transition state of the model reaction, addition of CH2O and CH2CH(OSiH3), the interbond energy IBE is negative between the σ-bonding orbital at the Z-position of the enolate terminal and π CO ∗ , and positive between that at the E-position and π CO ∗ . These results led us to predict that the electron-donating σ-bond at the Z-position enhances the reactivity. We calculated the enthalpies of activation of the reactions of a variety of the R-substituted silyl enolates and confirmed the prediction by showing that the reactivity of the Z-isomers relative to that of the E-isomers increases with the energy of the bonding orbital of the σ bond at the Z-position (the axial position at the transition state of the chair form). We demonstrate that the geminal bond participation is general not only to the pericyclic reactions but also to the aldol reaction, which is one of the most fundamental C–C bond forming reactions.