Chiral Urea-Catalyzed Asymmetric Mannich Reaction of 3-Fluoro-oxindoles with alpha-Amidosulfones: Synthesis of Optically Active alpha-Fluoro-beta-amino-oxindoles

The asymmetric Mannich reaction of 3-fluorooxindoles and alpha-amidosulfones catalyzed by a chiral urea catalyst derived from quinine in presence of K3PO4 was developed. Through the asymmetric reaction, a series of alpha-fluoro-beta-amino-oxindoles, containing a tertiary carbon stereocenter, could be obtained in high yields (up to 95%) with high enantioselectivity (95%) and diastereoselectivity (>99:1). Such alpha-fluoro-beta-amino-oxindole compounds are expected to become candidates in the field of medicine.