The direct syn-aldol and anti-Mannich reactions catalyzed by axially chiral amino sulfonamide and contrasts with proline catalysis: Insight from a computational study

Quantum mechanical calculations have been performed to study the stereoselectivities in the direct aldol and Mannich reactions involving special electrophiles such as glyoxylate, glyoxamide and sterically more hindered ketimine. The opposite diastereoselectivities in the axially chiral amino sulfonamide and proline-catalyzed aldol and Mannich reactions have been well reproduced by the density functional theory methods at the BH and HLYP/6-31G** computational level. The origin of the unusual selectivities for the axially chiral amino sulfonamide catalysis can be ascribed to the remoter distance between the bifunctional amino and acid groups in the catalysts in comparison with the traditional proline catalysis.