Organocatalytic Asymmetric [3 + 2] Cycloaddition of <i>N</i>-2,2,2-Trifluoroethylisatin Ketimines with β-Trifluoromethyl Electron-Deficient Alkenes: Access to Vicinally Bis(trifluoromethyl)-Substituted 3,2′-Pyrrolidinyl Spirooxindoles

Abstract

N-2,2,2-Trifluoroethylisatin ketimines with β-trifluoromethyl enones, 3-trifluoroethylidene oxindole, and 3-trifluoroethylidene benzofuranone can undergo asymmetric [3 + 2] cycloaddition, catalyzed by chiral bifunctional squaramide-tertiary amine catalysts, affording a wide spectrum of 3,2'-pyrrolidinyl spirooxindoles. The significance of this protocol is highlighted by its extremely high efficiency in the construction of the structurally diverse spirocyclic oxindoles, bearing a vicinally bis(trifluoromethyl)-substituted pyrrolidine moiety, including four contiguous stereocenters, in high yields with excellent stereocontrol.