Efficient construction of biologically important functionalized polycyclic spiro-fused carbocyclicoxindoles via an asymmetric organocatalytic quadruple-cascade reaction

Abstract

An efficient construction of highly functionalized polycyclic spiro-fused carbocyclicoxindoles has been developed via an asymmetric organocatalytic quadruple domino reaction of (E)-3-(2-hydroxybenzylidene)oxindole derivatives and two molecules of α,β-unsaturated aldehyde under quadruple iminium–enamine–iminium–enamine catalysis. The complex cascade products bearing a spiro quaternary center and five contiguous stereocenters were obtained in moderate to high yields (up to 90%) with good diastereoselectivities (up to 8 : 1) and excellent ee values (up to 99% ee). The structure and absolute configuration of the products were confirmed by NMR spectroscopy and single crystal X-ray analysis. In addition, the biological study showed that these compounds had moderate antitumor activities in the micromolar range.