Research On Alkyl Acylation Of Olefins Catalyzed By Oxidative N-Heterocyclic Carbine Organocatalysis Based On Intermolecular Hydrogen Atom Transfer Process

As an important chemical,organic halides are mainly reflected in two aspects:in the field of organic synthesis,organic halides are important synthetic intermediates and target products,and basic raw materials for the formation of carbon-carbon,carbon-oxygen and carbon-nitrogen bonds.In the field of drugs,the introduction of halogen atoms can significantly improve drug drugability,and halogen is the most important element in drug molecules next to carbon,hydrogen,oxygen,nitrogen,etc.At present,more than 40%of small-molecule drugs on the market contain halogen atoms.As intermediates of organic synthesis,amidohalides are widely used in the synthesis of medicine,pesticides and other fine chemicals.Dichloromethyl,a structural unit,exists widely in some bioactive molecules such as drugs,natural products and pesticides.In addition,dichloromethyl functional groups can also be converted into other different functional groups by various chemical means.More and more synthetic chemists pay attention to the bifunctional reaction of olefin because it can introduce two different functional groups simultaneously.In recent years,the bifunctional reaction of olefin catalyzed by N-heterocyclic carbine has made great progress.Therefore,it is of great significance to further realize the reaction of dichloromethyl radical mediated by N-heterocyclic carbine to participate in different bifunctional groups of olefin dichloromethyl acyl groups.In this paper,we report the catalytic difunctionalization of alkylacyl groups of alkenes by oxide N-heterocyclic carbine based on the intermolecular hydrogen atom transfer（Hydrogen atom transfer,HAT）process.In this reaction,we use tert-butyl peroxy ester as exogenous single electron oxidant,cheap and easy to obtain dichloromethane as dichloromethyl radical source and solvent,and use alkenes and aldehydes as reaction substrate,and finally realize the different difunctional group of dichloromethyl olefin,and obtain a series of aryl ketones containing the structural unit of dichloromethyl.In addition,we also used this reaction to carry out late structural modification on some olefin compounds containing drug skeleton,and successfully introduced the dichloromethyl structural unit into the complex molecular structure containing drug skeleton efficiently and conveniently.Therefore,this method provides a new idea and strategy for introducing dichloromethyl into some compounds containing complex molecular structure.In addition,we also scaled up the reaction and still obtained the target product of alkyl acylation of olefin with good yield.At the same time,the derivatization of the reaction product is studied,and the expected target product can be obtained with excellent reaction yield.In addition to the above research content,we also studied some other inert solvents（such as CHCl₃,CH₂Br₂,1,4-dioxane,THF）in this kind of intermolecular hydrogen atom transfer（HAT）reaction.The target products of different difunctional groups of olefin alkyl acyl groups can be obtained successfully with moderate reaction yield.Finally,in order to explore the reaction mechanism,we also carried out free radical inhibition experiment and free radical bell experiment.Preliminary mechanism studies indicate that the reaction undergoes a radical process.