The Research Of Dearomative [3+2] Cycloaddition Reaction Of Benzazoles With D-A Oxiranes

As an important structural unit,oxygenated five-membered heterocyclic compounds are widely found in natural products and active drug molecules,and these compounds exhibit various medicinal values in anticancer,antiviral,antibacterial and anticonvulsant applications.Because oxazole skeleton is one important nitrogen-oxygen five-membered heterocyclic skeleton,so oxazole derivatives usually have significant application value,and they are often found in many important fields such as organic synthesis,analytical detection,and biomedicine.As we all known,D-A ethylene oxide is an important 1,3-dipole,and it can synthesize a variety of oxygen-containing five-membered heterocyclic compounds by using the[3+2]cycloaddition reaction with various unsaturated double bond compounds.Therefore,finding a green and efficient method to synthetic five-membered nitrogen-oxygen heterocycles by[3+2]cycloaddition reaction of D-A ethylene oxide with C=N double bond has important significance and development prospects.In this paper,benzothiazole and D-A ethylene oxide were selected as starting materials.Under the catalysis of Lewis acid Sc?OTf?₃,D-A ethylene oxide was cleaved by selective C-C bond to form carbonyl ylide intermediate,then the intermediate was effected with the C=N in the thiazole structure by dearomatized[3+2]cycloaddition reaction to obtain a series of benzoxazolo[3,2-c]oxazole compounds.Under the optimal reaction conditions,the benzoxazoles modified with different functional groups and different types of D-A ethylene oxide substrates were obtained in the presence of the catalyst Sc?OTf?₃ with an isolated yield up to 96%and dr value was>20:1.Finally,the relative configuration of the cycloaddition product was determined by single-crystal X-ray diffraction anaiysis.In the next derivative experiment,the functional group is converted at different temperatures,and NaBH₄ can selectively reduce the monoester group and the diester group to obtain a monohydroxy reducing compound and a bishydroxy reducing compound respectively.Finally,for some of the newly synthesized compounds in the article,we also characterized them by NMR and high resolution.In conclusion,we have developed a new method for the synthesis of some benzoxazoloxazole compounds by dearomative[3+2]cycloaddition of benzoxazoles with D-A oxirane.The investigation of asymmetric[3+2]cycloaddition of D-A ethylene oxide and C=N double bond has not been reported.In combination with the background of our group of the asymmetric reaction research.Finally,we also carried out asymmetric catalysis studies about this reaction.Unfortunately,after screening ligands and catalysts we have not obtained the desired results,and now the asymmetric work of D-A ethylene oxide is still under study.