DMAP-catalyzed decarboxylative [3+2] cycloadditions: A strategy for diastereoselective synthesis of trifluoromethylated chromanone-fused pyrrolidinyl spirooxindoles

Abstract

Inspired by the chemistry and biology of fluorine-containing molecules, chromanones and pyrrolidinyl spirooxindoles, herein we report a highly diastereoselective [3 + 2] cycloaddition reaction of commercially available 3-carboxylic acid chromones and N-2,2,2-trifluoroethylisatin ketimines as azomethine ylide precursors in the presence of the catalyst DMAP, which enabled diversity-oriented synthesis of a series of potentially bioactive scaffolds containing CF3, chromanone and pyrrolidinyl spirooxindole with high efficiency (up to 87% yield and 15:1 diastereomeric ratio). The high efficiency of the cycloaddition relies on the use of a carboxylic acid-activation and then decarboxylation strategy for the less reactive chromones. In particular, this is the first construction of CF3-containing multiple rings-fused pyrrolidinyl spirooxindoles, bearing four contiguous stereogenic centers including one tetra substituted carbon, which might be valuable in medicinal chemistry.