Chiral Squaramide Catalyzed Asymmetric [3+2] Cycloaddition Reaction for Synthesis of Trifluoromethylated Barbituric Acid Derivatives

A squaramide catalyzed asymmetric Michael/Mannich [3+2] cycloaddition reaction between N-2,2,2-trifluoroethyl isatin ketimines and barbiturate-based olefins was developed. The corresponding trifluoromethylated dispirobarbituric acid derivatives containing three stereocenters were obtained in excellent yields and stereoselectivities (up to 99% yield, 99:1 dr and >99% ee). In addition, the gram-scale reaction also achieved with excellent yield and stereoselectivity.