Formal [2+1],[4+1] Annulations For Diastereoselective Construction Of Spirocyclic Oxindoles

Spirocyclic oxindoles are important organic structural units,which are widely present in numerous bioactive natural products and pharmaceuticals.Among them,spiro-epoxyoxindoles and dihydrobenzofuranspirooxindoles are not only identified as special structural units with significant biological activity,but also identified as very valuable intermediates due to their inherent ring tension and easy to undergo a variety of chemical transformations,In this paper,based on sufficient literature research,according to the domestic and foreign cutting-edge research trends,carefully conceived and designed synthesis strategies and experimental ideas,around solvent-free grinding conditions,carried out the synthesis of two kinds of spirocyclic oxindoles compounds:（1）By using 3-chlorooxindoles compounds and various substituted aryl aldehydes,a series of trans spirocyclic oxindoles derivatives have been synthesized by Darzens type[2+1]cyclization reaction under the action of the base.The yield and diastereoselectivity are good to excellent;（2）Using a-chlorooxindoles with a series of substituted salicylaldehydes as starting materials,firstly through[2+1]epoxidation reaction,followed by intramolecular nucleophilic addition to lead to ring opening of propylene oxide and ring formation of furan.Finally,a series of cis dihydrobenzofuranspirooxindoles compounds were constructed by formal[4+1]cyclization.The yield and diastereoselectivity are good.In this paper,63 new compounds were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR,HSBC,HSQC,HRMS,and X-Ray.The advantages of this new procedure feature are mild reaction conditions,simple operation,good yield,readily available inexpensive starting materials,gram-scalability,the good economy of atoms,and being friendly to the environment.These reactions enriche and extend the synthesis methodology of spirocyclic oxindoles.