Asymmetric Aminalization via Cation-Binding Catalysis

Asymmetric cation-binding catalysis, in principle, can generate chiral anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected alkyl- and aryl-substituted alpha-amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantio-selectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone-fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield.