The Reaction Of C(sp~3)-H Functionalization By 2-methyl-quinoline And Acetophenone Without Transition Metal Catalysis Was Studied

In organic synthesis,selective C(sp3)-H activation has always been a challenging area.The active research directions mainly include(1)selecting substrates with active C(sp3)such as 2-methylquinoline,phenylacetone,phenylacetone,etc.to realize such reactions under relatively simple and easy conditions.(2)for general C(sp3),this type of reaction can be achieved by selecting appropriate transition metal catalysts or other relatively harsh reaction conditions.Therefore,it is of great significance for medicine and other fields to select substrates with relatively active C(sp3)to realize more kinds of functional groups under simple and mild conditions.The structure of isoxazole is a key pharmacophore of many drug molecules.The traditional method of constructing the structure of isoxazole mainly involves the oxime of reactants in advance or the use of transition metal catalysts.It is crutial to synthesize isoxazole directly through C(sp3)-H functionalization.Therefore,without the use of transition metal catalysis to achieve such hydrocarbon functionalization has great application prospects.In the presence of TfOH,we successfully developed a strategy to directly synthesize 3-(quinoline-2-group)isooxazole by activating 2-methyl quinoline through C(sp3)-H bond and 1,3-dipole ring addition reaction with terminal alkyne.All kinds of aromatic and aliphatic terminal acetylene compounds are tolerant to this reaction,and the product yield is moderate to good.Sulfur ester is widely used in medicine and pesticide because of its special structure,which can lead to physiological activity of some compounds.Many synthetic methods reported in the papers mainly used thiol,thiophenol and thioether to construct corresponding thioesters,while few methods directly used sulfoxide as thiomethyl source to synthesize thioesters.We developed a method to synthesize relatively clean thioester derivatives by using sulfoxide as a thiomethyl source and activating 2-methyiquinoline through C(sp3)-H bond.In addition to dimethyl sulfoxide,dibenzyl sulfoxide and others can also complete the reaction,and the yield is medium to good,a total of 29 substrates were expanded.Refer to the literature investigation and related mechanism exploration experiments,we come up with the probable mechanism.Dimethyl sulfoxide(DMSO)can be applied to solvents and a variety of reagents in organic synthesis.Because dimethyl sulfoxide is cheap and easy to obtain,and easy to operate,the application of dimethyl sulfoxide to chemical reactions in recent years has aroused the interest of chemists,and there are a lot of reports on the reaction realized by dimethyl sulfoxide as reagent.For instance,dimethyl sulfoxide is used as sulfur methyl source,oxygen source,and the like.In this part,dimethyl sulfoxide was used as a thiomethyl source,and aryl methyl formate derivatives were synthesized under the mediation of boric acid through activation of C(sp3)-H bond of aryl methyl ketone.25 substrates were tested and the yield was medium.Through mechanism exploration and literature research,we proposed the possible reaction mechanism.