Organocatalytic Enantioselective Synthesis of 1,3-Oxazinanes and Hexahydropyrimidines via [4+2]-Annulation of Cyclic N-Sulfimines

The first asymmetric synthetic method for enantioenriched 1,3-oxazinane and hexahydropyrimidine derivatives via the asymmetric [4+2]-annulation of cyclic N-sulfimines has been established. The reaction of cyclic N-sulfimines with delta-hydroxy-alpha,beta-unsaturated ketones afforded a wide range of enantioenriched polyheterotricyclic 1,3-oxazinane derivatives in high yields with good to excellent enantioselectivities in the presence of a cinchonidine-derived squaramide catalyst. This approach has been extended to the asymmetric organocatalytic [4+2]-annulation of cyclic N-sulfimines with delta-NHTs-alpha,beta-unsaturated ketones providing enantioenriched hexahydropyrimidines. In addition, the asymmetric [4+2]-annulation of delta-hydroxy- and delta-NHTs-alpha,beta-unsaturated ketones gave their corresponding enantioenriched 1,3-oxazinane and hexahydropyrimidine derivatives with different absolute configurations.