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

A mild and organocatalytic synthetic method for enanthoenriched 1,3- oxazinane and hexahydropyrimidine derivatives via the asymmetric [4+2]-annulation of cyclic N-sulfimines has been established. The [4+2]-annulation reactions of cyclic N-sulfimines with δ-hydroxy-α,β-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 cinchonidine-derived squaramide as a catalyst.

Abstract

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 δ-hydroxy-α,β-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 δ-NHTs-α,β-unsaturated ketones providing enantioenriched hexahydropyrimidines. In addition, the asymmetric [4+2]-annulation of δ-hydroxy- and δ-NHTs-α,β-unsaturated ketones gave their corresponding enantioenriched 1,3-oxazinane and hexahydropyrimidine derivatives with different absolute configurations.

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