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 α‐amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantioselectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone‐fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield. Aminal instinct: Diverse chiral acyclic aminals were prepared in excellent yields and enatioselectivities (up to 99 % ee) by cation‐binding catalysis. In particular, the present protocol renders unprecedented and challenging substrate scope, particularly, aliphatic substrates, which are predominant in molecular scaffold of many natural products. The synthetic utility of the current methodology was also demonstrated by preparing biologically relevant products that possess aminal and polyheterocyclic cores.