Stereoselective synthesis of spirooxindole derivatives using an organocatalyzed tandem Michael-Michael reaction

A highly efficient stereoselective method for the synthesis of functionalized spirooxindole derivatives with three stereogenic centers was realized through an organocatalytic tandem Michael-Michael reaction. By employing (S)-alpha,alpha-diphenylprolinol trimethylsilyl ether as the catalyst and N, N'-bis[3,5-bis(trifluoromethyl) phenyl] thiourea as the cocatalyst, the reaction between N-tritylisatylidenemalononitriles and (E)-7-alkyl-7-oxohept-5-enals yields the desired spirooxindole products in good yields (76-95%) and with excellent diastereoselectivities (up to 97 : 3 dr) and enantioselectivities (up to 98% ee), which can be stereoselectively converted into the spiro[indoline-3,8'-isoquinoline] derivative through an intramolecular reductive amination reaction.