Asymmetric synthesis of trifluoromethyl-substituted 3,3′-pyrrolidinyl-dispirooxindoles through organocatalytic 1,3-dipolar cycloaddition reactions

Abstract

Unprecedented asymmetric exo′-selective [3 + 2] cycloaddition reactions of CF₃-containing isatin-derived azomethine ylides with methyleneindolinones have been disclosed. Under bifunctional organocatalysis by cinchona-derived squaramide catalysts, a series of potential biologically important trifluoromethylated 3,3′-pyrrolidinyl-dispirooxindoles were efficiently constructed in a highly stereoselective manner (84%–99% yields, up to >20 : 1 dr and >99% ee). The reaction leads to the formation of four contiguous stereogenic centers, including two adjacent spiro quaternary stereocenters.