Research On The Construction Of Benzo[b]azepine Skeleton Involved Sulfur Ylide

As the core skeleton,the benzoazepine skeleton is widely present in natural products with biological activity.However,the construction of benzoazepine skeleton remains a challenging task due to its unique structure.Although various strategies and methods have been developed,several longstanding problems,including tedious multi-step synthesis,harsh reaction conditions and complex activation pattern.Therefore,it is of great significance to develop an efficient method to construct the benzoazepine skeleton.In recent years,as a nitrogen-containing synthetic building block,vinyl benzoxazinone has been widely used in the construction of various natural products,which have potential physiological and pharmacological activities.However,its activation often requires the help of metal palladium species.Meanwhile,vinyl benzoxazinone often participates in the reaction as a 1,4-nitrogen-containing dipole,which limits its application.Based on this,we designed a kind of vinyl benzoxazinone MBH carbonates,which is expected to directly accept the attack of nucleophiles,and an in situ-generated 1,6-nitrogen-containing dipole could further participate in the cyclization reaction.It can effectively make up for the problem that vinyl benzoxazinones require metal activation and a single reaction site,providing an effective synthetic tool for the construction of nitrogen-containing midrings.Sulfur ylide can be used as a very important organic reagent in organic synthesis,participating in the synthesis and application of three-membered,four-membered,five-membered and even six-membered rings.Although[2+1],[3+1],[4+1]and[5+1]cyclization reaction types have been realized,there are almost no reports about the[6+1]cyclization reaction types.Based on the previous work,we use Fe（OTf）₂ to promoted the vinyl benzoxazinone MBH carbonates,then accepted the attack of sulfur ylide.Finally,we successfully synthesized a series of benzoazepines with moderate to excellent yields.Through this method,we have effectively synthesized important key intermediates of CCR5antagonists.Next,we also modified the skeleton of the product with a series of efficient oxidation rearrangement and tandem cyclization processes.This method has certain theoretical significance and practical value.It also provides an important case for the diversity construction of benzoazepine skeleton.