Diversity-Oriented Synthesis of Spirooxindoles via Asymmetric Organocatalytic Regiodivergent Cascade Reactions

A regiodivergent strategy for the asymmetric diversity-oriented synthesis of spirooxindoles via organocatalytic cascade reactions is developed. Two regioselective pathways can be precisely controlled with different aminocatalysts in the reaction of 2-hydroxycinnamaldehydes and β,β-disubstituted 3-alkylidene oxindoles. The cascade vinylogous Michael/oxa-Michael/aldol reactions gave spiro-bridged oxindoles bearing two adjacent quaternary stereocenters, while the cascade oxa-Michael/Michael reactions gave spirooxindoles. Moreover, during the synthetic application studies, an acid-catalyzed rearrangement of spiro-bridged oxindoles was found to yield biologically important 3-alkylidene oxindoles.