Two approaches toward the regio- and stereoselective synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro-[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles]

A regio- and stereoselective method for the synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]-pyrrolidine-1,3'-oxindoles] in 24–79% yields, based on the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with azomethine ylides generated in situ from benzylamines and isatins by refluxing in CH2Cl2 for 24 h has been developed. 3-Phenyl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles] were obtained in 36–71% yields via the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromene, isatins, and L-phenylglycine proceeding in EtOH at 60°C for 5 h. The resulting compounds exhibited cytotoxic activity against human cervical cancer HeLa cells in the micromolar concentration range.