Potassium <i>tert</i>-butoxide mediated stereoselective/direct Mannich reaction of α-substituted-γ-lactams with <i>in situ</i> generated aryl <i>N</i>-silyl imines

A potassium <i>tert</i>-butoxide (KO<i>t</i>-Bu)-mediated Mannich reaction between α-substituted-γ-lactams and <i>N</i>-silyl imines is reported. <i>N</i>-silyl imines are generated <i>in situ</i> from readily available aryl nitriles and directly combined with the lactams, without preformation of the lactam enolate, to afford the α-quaternary center-bearing Mannich bases in high yield and with high diastereoselectivity (24 examples). This reaction is shown to be catalytic with respect to KO<i>t</i>-Bu and the catalytic mechanism has been investigated using density functional theory calculations. The computational investigations suggest that the diastereoselectivity is controlled by explicit interactions between a binuclear potassium complex and both the imine nitrogen and the enolate oxygen atoms in the selectivity-determining transition states. The Mannich products are shown to be useful in accessing novel spirocyclic pyrrolidines.