Sc（OTf）₃-Catalyzed [3+2]-cycloaddition Of Nitrones With Ynones

Nitrogen heterocyclic compounds are one of the most important structural categories of chemical substances.They have a variety of biological activities and have superior pharmacological effects,especially in natural products,biological active structures and compounds related to drugs.In the past few decades,efforts have been made to develop new and effective methods to construct nitrogen-containing heterocycles.Nitrone compound is the nitrogen oxide of imine,which has attracted the attention of many scientists since its discovery.It is the key intermediate for the synthesis of a series of compounds containing nitrogen,oxyheterocyclic compounds such as pyrrolidine,piperidine and isoxazolidine.Nitrone can be used as an amphiphilic reagent to perform 1,3-dipole cyclization with olefins,dienes,conjugated olefins and other dipolophiles,and finally to construct a series of natural products and bioactive molecules with nitrogen heterocyclic framework.The purpose of this thesis is to construct an efficient methodology for the[3+2]-cycloaddition reaction of nitrone and alkynyl ketone,and to synthesize a series of azocyclic compoundsIn this paper,a new method for the synthesis of a series of azocyclic compounds by[3+2]-cycloaddition reaction catalyzed by Sc（OTf）₃between nitroketones with different substituents and alkynyl ketones with different substituents has been established.The main results are as follows:1.The[3+2]-cycloaddition reaction of nitrones and ynones under the catalysis of Sc（OTf）₃was optimized,and the synthesis method of 5-element azooxacyclic compound was established.The results of 39 substrate expansion tests show that this method has high substrate adaptability and the yield of product is between 18%-88%.2.The application of the cycloaddition reaction of nitrone and acetylenone developed in this paper was further expanded.A gram-scale experiment was carried out in this paper,and the target product was obtained with 83%yield.Then,the product was transformed to synthesize the divinylketone compound with 77%yield.Gram-scale experiments show that it has good stability and is suitable for large-scale preparation.The transformation experiment also indicates that this method can be applied and researched more widely.