Theoretical studies of stereoselectivities in the direct anti-Mannich and syn-aldol reactions catalyzed by axially chiral amino sulfonamide

The origins of the stereoselectivities in the axially chiral amino sulfonamide-catalyzed direct anti-Mannich and syn-aldol reactions have been studied with the aid of density functional theory method. Transition states of the stereochemistry-determining C–C bond-forming step with the enamine intermediate addition to the imine or aldehyde for the subject Mannich and aldol reactions are reported. BH and HLYP/6-31G** calculations provide a good explanation for the diastereoselectivities in the chiral amino sulfonamide-catalyzed anti-Mannich and syn-aldol reactions. Calculated and observed diastereomeric ratio and enantiomeric excess values are in good agreement.

Graphical abstractThe origins of the stereoselectivities in the axially chiral amino acid (S)-1 and amino sulfonamide (S)-2-catalyzed direct Mannich and aldol reactions have been studied theoretically. The most stable transitions states of the crucial C–C bond-forming steps for the Mannich and aldol reactions provide a good explanation for the opposite diastereoselectivities of the above two catalysts.Figure optionsDownload full-size imageDownload as PowerPoint slide