Bromofluorination Of Conjugated Dienes

Fluorine is the most abundant halogen element in the earth’s crust,but only more than 20 natural products containing fluorine have been found in nature so far.Introducing fluorine atoms into organic molecules can greatly change the physical and chemical properties of compounds,enhancing their lipophilicity,bioavailability,and metabolic stability.In recent years,fluorinated compounds have been widely used in the field of biomedicine,and their synthesis has received widespread attention.Allyl fluorides are an important class of fluorinated compounds.In addition to having fluorine atoms,their structure also contains a double bond,providing an opportunity for further functional group conversion.Traditional methods for synthesizing allyl fluoride mainly include the following two methods: one is to replace allyl electrophilic reagents with a nucleophilic fluorine source,and the other is to react with an electrophilic fluorine source through allyl silane or an allyl anion intermediate.However,both methods require pre functionalization of the substrate.In recent years,the strategy of synthesizing allyl fluorides through the activation of allyl hydrocarbon bonds has received widespread attention.However,the products obtained by this method are typically mixtures of linear and branched allyl fluorides.The fluorination bifunctionalization of conjugated dienes is an efficient method for the synthesis of allyl fluorides,but such reactions have rarely been reported and pose selectivity challenges.Conjugated dienes contain two double bonds,and there are multiple reaction sites.During the reaction process,there will be selectivity issues such as regio-,site-,and stereoselectivity.In this context,it is necessary to develop a selective and controllable fluorination bifunctionalization reaction of conjugated dienes,which will be an effective method for the synthesis of allyl fluorides.In this work,the 1,2-bromo fluorination of alkyl-substituted conjugated dienes has been achieved with excellent regioselectivity,stereoselectivity and high yield,using Nbromodialkylamine as electrophilic bromine reagent and iron fluoride as nucleophilic fluorination reagent.The mild reaction conditions and good functional group compatibility make this strategy an effective method for preparing allyl fluoride.The main content of this paper includes the following two parts:The first part introduces the methods of constructing allyl fluorides through nucleophilic substitution,electrophilic substitution,and other methods,as well as the research progress of halogenated bifunctionalization reactions of conjugated dienes.The second part: A detailed introduction to the research background,optimization of experimental conditions,substrate expansion,and mechanism exploration of this work.In this study,the chemical selectivity of the reaction is controlled by the steric hindrance effect of conjugated dienes,and the regioselectivity of the reaction is controlled by the differences in the properties of bromium ion intermediates under different conditions.Finally,the 1,2-bromofluoride reaction of conjugated dienes with high chemo-,regio-and stereoselectivity is successfully achieved.