Efficient enantioselective synthesis of CF2H-containing dispiro[benzo[b]thiophene-oxindole-pyrrolidine]s via organocatalytic cycloaddition

Abstract

An efficient and practical organocatalytic asymmetric [3 + 2] cycloaddition of difluoromethylated ketoimines and methyleneindolinones catalyzed by a quinine-derived squaramide has been disclosed. Under mild conditions, a broad range of CF₂H-containing dispiro[benzo[b]thiophene-oxindole-pyrrolidine]s bearing four adjacent chiral centers including two vicinal spiro quaternary stereocenters were obtained in high yields (up to 99% yield) with excellent diastereoselectivities (>20 : 1 dr, in all cases) and enantioselectivities (up to 99% ee).