Squaramide-Catalyzed Enantioselective Cascade Approach to Bispirooxindoles with Multiple Stereocenters

A bifunctional squaramide-catalyzed Michael/Michael cascade reaction for the construction of spirotetrahydrofuran bispirooxindoles was developed. The products were obtained in moderate to excellent yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, >99% ee). This straightforward process serves as a powerful method for the enantioselective construction of potentially bioactive bispirooxindoles in which two of the four contiguous chiral centers are spiro all-carbon quaternary centers on a single tetrahydrofuran ring. Meanwhile, the synthetic practicality of this methodology was illustrated by performing the reaction on a gram-scale with the same efficiency and stereoselectivity. (Figure presented.).