Research On The Tandem Heterocyclicization Reaction Of Ethyl Isocyanoacetate And Ortho-Quinone Methides

Heterocyclic structures are widely found in natural products and biologically active molecules,and have a very important position in the fields of medicine and pesticides.In addition,heterocyclic compounds are also important organic synthesis intermediates,which are widely used in organic chemistry,materials chemistry,medicinal chemistry and other fields.Among them,bisbenzopyran is the core structure of natural products such as albanol A,sorocenol E and australisin A.Such natural products show anti-cancer,anti-malarial,phytotoxicity,erythropoietin gene expression and acetylcholinesterase inhibition as well as other broad and diverse biological activities.Therefore,the development of new synthetic methods for bisbenzopyrans has attracted much attention.Isocyanoacetates are versatile organic synthons.Cycloaddition reaction based on isocyanoacetate is usually an effective method to synthesize simple five-membered heterocycles such as oxazole and imidazole.In addition,in this type of reaction,the ester group of isocyanoacetate usually only serves as an activating group and a substituent of the heterocyclic product without participating in the reaction.However,there are few reports on the efficient synthesis of complex and important polycyclic compounds using the tandem heterocyclization of isocyanoacetate.In this thesis,a diastereodivergent tandem heterocyclic reaction between isocyanoacetate and o-methylenequinone(produced in situ)is developed,which provides a highly efficient novel proptocol for the diastereoselective synthesis of dihydrooxazolobisbenzopyran derivatives.The reaction starts from simple and readily available raw materials,the diastereoselectivity of the reaction can be adjusted by changing the reaction conditions.A variety of bridged compounds can be constructed in a one-step domino transformation.In addition,the ester group of the isocyanoacetate serves as both an activating group and a reactive group in this reaction,which increases the complexity of the product structure and improves the reaction efficiency.