New insights on the origins of the stereocontrol of the Staudinger reaction: [2+2] cycloaddition between ketenes and N-silylimines

Density-functional theory studies on the [2 + 2] reaction between N-silylim ines and ketenes to form the corresponding a-azetidinones (beta -lactams) h elp to clarify several aspects an the mechanism of the Staudinger reaction. This reaction has been studied experimentally by Panunzio et al. It is sho wn that the formation of the 2-azetidinone ring takes place via two consecu tive reactions. The first reaction consists of the nucleophilic addition of the iminic nitrogen to the sp-hybridized carbon atom of the ketene, with s imultaneous migration of the silyl group from the imine to the oxygen atom of the ketene. This leads to silyl enol intermediates, in good agreement wi th the experimental results. Formation of the N-silylated beta -lactam take s place via a domino reaction consisting of a conrotatory thermal electrocy clization followed by a new silatropic rearrangement, It is also found that isomerization of the starting N-silylimine has a lower activation barrier than that associated with the formation of the C-N bond, which explains the stereochemical outcome experimentally observed. Further considerations on the asymmetric torquoelectronic effects involved in this reaction are also reported.