TWO APPROACHES TO REGIO- AND STEREOSELECTIVE SYNTHESIS OF N-UNSUBSTITUTED 3-ARYL-4-(TRIFLUOROMETHYL)-4H-SPIRO[CHROMENO[3,4-c]PYRROLIDINE-1,3'-OXINDOLES]

Abstract

A regio- and stereoselective method for the synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]pyrrolidine1,3'-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.