Squaramide-Catalyzed Asymmetric Michael Addition/Cyclization Reaction for the Synthesis of Chiral Bisspiro Barbituric
1Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
An efficient stereoselective strategy for the synthesis of chiral bisspiro barbituric acid-oxindole derivatives was developed. The asymmetric Michael addition/cyclization tandem reaction between benzylidene barbituric acids and oxindolylmalonitriles was catalyzed by squaramide catalyst, and the corresponding spirocyclic products were obtained in good-to-high yields (up to 97%) with excellent stereoselectivities (up to >99% ee, >20:1 dr). At the same time, the practicality of the reaction was verified by the gram-scale preparation reaction.
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