Study On The Selective Difluorochloroethylation Reactions Of Amides With Hypervalent Iodine Reagent

Fluorine atoms has a high ionization potential,higher electronegativity,and smaller atomic radius.The introduction of fluorine atoms into organic molecules can significantly enhance their lipophilicity,metabolic stability and acidity.Due to this important characteristic,fluorine containing organic compounds have been widely used in various fields such as pharmaceutical and materials.Since there are fewer natural organic fluorides in nature,designing and synthesizing various new fluorine-containing frameworks and using them in the synthesis of drugs has always been a research hotspot in organic fluorine chemistry.Organic hypervalent iodonium salts have been widely applied and become t he most active research field in modern organic synthesis chemistry due to their characteristics of easy preparation,and environmental friendly feature.Hyperval ent iodine reagents as functional group conversion reagent,which can be used a s reaction carriers for fluorine-containing dicing to realize further research on fl uorine chemistry.In recent years,with the development of various CF₃,CH₂CF₃,SCF₃ reagents,our research group proposed and synthesized a chlorodifluoroeth yl hypervalent iodine reagent,and explore the reactivity of this reagent with am ide.In this thesis,chlorodifluoroethyl hypervalent iodine reagent and amides are used as reaction substrates.The study found that by adjusting the reaction solv ent at room temperature,without the need for additional additive and transition metals,we have achieved N-Chlorodifluoroethylation and O-Chlorodifluoroethylat ion of amides.When we using DCM as regent,we can obtain difluorochloroeth yl substituted amides in high yield.On the other hand,when we used acetonitri le as the solvent,we got difluorochloroethyl ester product.The strategy has the characteristics of very good substrate applicability and yield,and provides an ef ficient way for the synthesis of difluorochloroethyl reaction.By introducing chlo rine atoms,this reaction can not only realize a specific geminal difluorination r eaction,but also provide new reaction sites for multiple transformations.