Synthesis Of Heterocycles Containing Nitrogen And Oxygen By Cyclization Of N-propargylanilines

Nitrogen and oxygen heterocyclic compounds containing nitrogen and oxygen atoms at the same time,due to structural diversity,show a wide range of biological activities,and have a wide range of applications in medicinal chemistry.Therefore,it is important to develop efficient and green synthetic methods for nitrogen and oxygen heterocyclic compounds.Application value.In the preliminary research,the research group developed the intramolecular hydrogenationredoxcrossdehydrogenationcouplingof N-（3-hydroxypropyl）-N-（2-propargyl）aniline（Intramolecular Hydroarylation-Redox CDC,referred to as IH-Redox CDC）reaction,through intramolecular aromatic hydrogenation of propargyl,intramolecular C-O cross dehydrogenation coupling,continuous cyclization to build a tricyclic skeleton,to achieve efficient synthesis of tricyclic 1,3-oxazine nitroxide.In this paper,2-（（N-phenyl-N-propargylamino）methyl）phenol compounds are used as substrates,and different cyclization pathways of the same substrate are regulated by ligands to realize different types of nitroxide heterocyclic compounds.The specific research content includes the following two aspects:1.Intramolecular IH-Redox CDC reaction to synthesize tetracyclic 1,3-oxazine nitroxide heterocyclic compoundsNo ligand is added,only CuBr is used to catalyze and activate2-（（N-phenyl-N-propargylamino）methyl）phenolic compounds.Intramolecular IH-Redox CDC reaction occurs and continuous cyclization generates a tetracyclic ring 1,3-oxazine nitrogen and oxygen heterocyclic compounds.In this paper,the synthesis of 8 tetracyclic 1,3-oxazine nitroxide heterocyclic compounds has been achieved,and the yield is 7%-40%.It is speculated that the tetracyclic structure is unstable,which is easily decomposed in the reaction system,resulting in low product yield.2.Intramolecular cyclization to construct a seven-membered benzonitrazine heterocyclic compoundAfter adding the PCy₃ ligand to the reaction,the PCy₃ ligand first forms a copper metal organic complex with CuBr,and then catalyzes the intramolecular nucleophilic cyclization reaction of the phenolic hydroxyl group to the alkynyl group in the substrate to obtain the benzonitrazine seven-membered heterocycle.Cyclic compound.In this paper,13benzonitroxide seven-membered heterocyclic compounds have been realized with a yield ranging from 29%to 94%,which has good substrate applicability.Through the high-resolution mass spectrometry study of the formed copper metal-organic complex,it is preliminarily speculated that the formed metal-organic complex is[Cu（PCy₃）₂]Br.