Construction Of Polycyclic Spirooxindoles Via Cascade Reactions

Spirooxindoles are privileged structural motifs present in awide range of natural products and pharmaceuticals,and exhibit significant biological activities.Spirooxindoles with different structures have distinct biological activities.Consequently,extensive efforts have been devoted to the synthesis of spirooxindoles with complex and diverse structures,and some elegant achievements have been made.Among the approaches for the efficient synthesis of such kind of compounds,cascade strategy serves as be one of the most direct and effective methods.In the second part,the first DBU-catalyzed Michael/Pinner/isomerization cascade reaction of 3-hydrooxindoles with isatylidene malononitriles was developed,and the corresponding bispirooxindoles containing a fully substituted dihydrofuran motif were obtained in up to 92%yield.In addition,the asymmetric version of the cascade reaction was achieved.In the third part,we envisioned that combining the two motifs into one complex molecule would generate an array of novel and interesting compounds,which may have new or improved biological activities,to this end,an efficient Cu?OTf?₂-catalyzed Friedel-Crafts alkylation/cyclizaiton sequence of 3-substituted indoles with isatin-derived oxodienes was developed,and a series of structurally complex and diverse pyrrolo[1,2-a]indole spirooxindoles were first obtained in up to 99%yields.This protocol proved to be quite general and robust for the synthesis of 9H-pyrrolo[1,2-a]indoles.In the last part,a TfOH-catalyzed highly diastereoselective Michael addition/ketalization sequence of 3-hydroxyoxindoles and ortho-hydroxy-chalcones was developed,leading to biologically important bridged ketal spirooxindoles in moderate to excellent yields.Meanwhile,the highly diastereoselective TfOH-catalyzed Michael addition/N,O-ketalization sequence of 3-amino-oxindoles and ortho-hydroxychalcones was also achieved,delivering a wide range of bridged cyclic N,O-ketal spirooxindoles with complex and strained structures in 41-97%yields.The sailent features of this reaction includes:1)metal-free,2)highly diastereoselective,3)products contained three stereocenters and two of them were quaternary carbon centers,4)simultaneous formation of two new rings,one of which is bridged ring.