Study On Electrochemical Halogenation And Fluoroalkylation

Organic halides are essential compounds for drug,agriculture,and material development.They are also important building blocks in organic synthesis and the production of chemicals.The introduction of halogen atoms may change organic compounds'physical and chemical properties to achieve unique properties.In particular,the radioactive halogen isotope labeling of organic compounds plays an important role in nuclear medicine,molecular imaging,medical,scientific research,and other fields.The traditional method of introducing halogen atoms into organic compounds usually requires the use of toxic and dangerous reagents such as halogen gas,hydrohalic acid,and strong oxidant,which is not only harmful to the environment but also lead to low selectivity and poor atomic economy.Electrochemical organic synthesis uses clean electrons as redox agents to realize electron transfer on the electrode surface,which is green,safe,and environmentally friendly.Its application in halogenation reaction has many outstanding advantages.In this paper,several electrochemical reactions were explored to introduce halogen atoms into organic molecules,including the electro halogenation addition reaction of unsaturated bonds,the electrochemical halodesilylation of arylsilane,the electrochemical fluorination reaction of benzyl sp~3 C-H bond and the electrochemical fluoroalkylation cyclization reaction of olefin azide.The details are as follows:In the first part,we studied a method of electrochemical dihalogenation of olefins and alkynes without oxidants and transition metal catalysis.This halogenation method is based on inexpensive lithium salts as halogenation reagents and acetic acid as reaction solvent to achieve dibromination,dichloration,and diiodination of unsaturated bonds under mild conditions.This method has wide substrate adaptability,high reaction efficiency,and simple reaction condition.This reaction works well at the gram scale.In addition,we also explored and verified the reaction mechanism.In the second part,we studied a green and safe electrochemical halodesilylation method of aryltrimethylsilane.This method uses stable and easily available aryl silanes as reactants,metal halogenated salt as halogen source and supporting electrolyte,and can realize the preparation of chlorinated,brominated,and iodized aromatics.The reaction conditions are mild,safe,and green,and the conversion rate is high.Besides,the gram scale electrochemical halodesilylation reaction also can be conducted.Through this electrochemical method,we also completed the radioactive iodine labeling of aryl compounds,especially some bioactive molecules.Finally,we speculated on the possible mechanism of this reaction.In the third part,we developed an electrochemical fluorination method of benzyl sp~3 C-H bond and fluorination of carboxylic acid derivatives with?aryl groups.This method uses potassium fluoride as a fluorine source and electrolyte,avoiding hydrogen fluoride or its organic base complex commonly used in traditional electrochemical fluorination methods.This method has low toxicity,safety,little environmental harm,and does not need special corrosion-resistant equipment.In the meantime,we also expand this reaction scale to gram level.In addition,we achieved electrochemical fluorine-18 radioisotope labeling of some representative compounds.Finally,we conjectured the possible reaction mechanism.In the fourth part,we describe a green,safe and sustainable electrochemical strategy,which can realize the trifluoromethylation or difluoromethylation of vinyl azides.According to different starting materials,electrochemical fluoroalkylation,cyclization,or dearomatization products can be obtained.This method uses inexpensive and bench-stable sodium fluoroalkyl sulfonate as a fluoroalkylation reagent,which provides a catalyst-free and oxidant-free way for synthesizing fluorine-containing nitrogen heterocyclic compounds.We studied the substrate applicability of this method and completed the gram reaction experiment.Finally,the reaction mechanism was verified by voltammetric cycle studies and control experiments.