Intermolecular Bromoazidation Of Alkenes With The Assistance Of Lewis Acid

Difunctionalization of alkenes through radical approach has been widely applied in the synthesis of pharmaceuticals and bioactive natural products as it allows for the rapid introduction of two functional groups into the target molecules,and thus dramatically enhances the molecular complexity Among these difunctionalization reactions,haloazidation of alkenes has received much attention in recent years.This reaction can incorporate a halo atom adjacent to the newly formed azido group.At the same time,these functional groups with special chemical properties can participate in various further functional group interconversions.The compounds obtained by the haloazidation reaction can serve as new intermediates in chemical industry,medical drugs,pesticides as well as other fields that is of great significance for organic synthesis.However,currently there are several major isuues for the intermolecular haloazidation of alkenes:1)During the reaction,safety problems are existed.The haloazidation reaction often requires the addition of pre-synthesized halogen azides to the olefin.XN₃（X=Cl,Br,I）could generate hydrazoic acid in situ with strong volatility and potential chemical toxicity;2)The regioselectivity of the haloazidation reaction would be greatly effected by different chemical environment,resulting in the substrate scope limited to the styrene derivatives and only a few examples for the unactivated alkenes;3)Although some methods have been developed to realize the regioselective azidochlorination reactions and azidoiodination reactions,the azidobromination reactions are difficult in achieving a high regioselectivity due to the multiple reaction pathways.In this thesis,an intermolecular bromoazidation of alkenes has been realized via azide radical intermediates and N-bromodialkylamine was utilized as halogen atom source with the assistance of Lewis acid.The regioselectivity of bromoazidation reaction is effectively controlled by this new method,which provides a new and efficient method for the synthesis of anti-Markov bromine azide compounds.The first part:we briefly summarized the development of intermolecular bromoazidation of alkenes.At the same time,according to the different reaction mechanisms,the bromoazidation reaction of alkenes is classified respectively.The second part:the research background,condition screening,substrate expansion,mechanism research and other aspects of this research project are introduced in detail.This method can be widely used in both activated olefins and unactivatedolefins by radical strategy.At the same time,terminal olefins,internal olefins,and multiple functional group-substituted olefins are compatible,and the functionalization of sugar derivatives has also been realized to obtain bromoazidation products with diverse structures.The third part:Structure analysis of the synthesized substrates and target compounds through ¹H NMR,¹³C NMR,IR,HRMS and other characterization methods.