Study On The Cyclobutenone Reaction Of Sulfilimines With Cyclobutanone:Access To Benzazepinones

As nitrogen heterocyclic compounds with important research value in biomedicine and chemical synthesis,the effective synthesis methods of benzazepine and pyridoazepine derivatives have been very popular.In view of the great research value of synthesizing such compounds,we combined the research group’s research on ketene in recent years,and tried to introduce sulfilimines as the nitrone transfer reagent in the reaction,and cyclobutenone as the ketene precursor to explore a new way to prepare benzazepine.This paper can be mainly divided into the following two contents:(1)The research significance and various effective synthesis methods of benzoazepines were reviewed.The characteristics of cyclobutenone and sulfilimines were introduced,and the background research and analysis of the cycloaddition reactions involved were studied respectively.(2)Metal-free catalyzed [4+3] cycloaddition of sulfilimines and cyclobutenone was achieved.By optimizing the reaction conditions such as catalyst,solvent,temperature and equivalent,the optimal yield of benzoazepine product was 91%,and the optimal yield of pyridoazepine product reached 69%.The reaction raw materials are stable and easy to prepare,no catalyst needs to be added.At the same time,the reaction has the advantages of good functional group tolerance and high yield,and successfully passed the gram-scale reaction and derivatization application experiments.Then,two possible reaction pathways for this reaction were speculated.First,the cyclobutenone is heated to open the ring and generate the ketene intermediate.The sulfilimines then performs a nucleophilic attack on the intermediate to add to the intermediate.The polarized N-S bond is then cleaved and cyclized to give the product.The second route involves the formation of an aziridine analog intermediate followed by a rearrangement and aromatization.