Radical Iododifluoroalkylation Of Cyclopropene

Due to the small steric hindrance of the difluoromethylene structural unit,its introduction into the drug molecule can significantly change the pharmacological activities of the drug such as lipophilicity,bioavailability and metabolic stability,and will not affect the role of other pharmacophores so as to maximize the efficacy of the drug molecule.Therefore,the development of efficient and simple gem-difluoroalkyl introduction methods has attracted more and more attention of chemical workers in recent years.Alkynes and alkenes are bulk chemical raw materials.Their radical bifunctionalization reaction can introduce any two functional groups into the unsaturated bond at the same time,which provides an effective strategy for the introduction of gem-difluoroalkyl.Halogenated gem-difluoramide or halogenated gem-difluorocarbonyl ester is a commercialized reagent,which is easy to obtain,and is an excellent gem-difluoroalkyl radical precursor.Its gem-difluoroalkylation functionalization with alkenes and alkynes has become a direct and effective method to synthesize compounds containing gem-difluoroalkyl.At present,the hydrodifluoroalkylation,carbodifluoroalkylation and oxydifluoroalkylation have been successfully realized.However,the reactions mainly focused on chain unsaturated hydrocarbons,cyclic unsaturated compounds,especially strain cyclic olefins,have not been realized.As the smallest unsaturated cyclic compound,cyclopropene has a large ring strain,so it has a very high reactivity,and can take place a variety of reactions,such as carbon metallization,hydrogen metallization,heteroatom metallization,polymerization,ring-opening isomerization,etc.However,there are few studies on the radical functionalization of cyclopropene.In this thesis,we used cheap and readily available manganese catalyst to realize the iododifluoroalkylation reaction of cyclopropene and ethyl iododifluoroacetate/α-iododifluoroacetamide under visible light irradiation,and efficiently synthesized a series of difluoroalkyl substituted cyclopropane derivatives.The mechanism study showed that the reaction experienced a rare cyclopropene radical addition reaction,and the light and dark control experiment results confirmed that the reaction did not experience the traditional chain reaction pathway.The method has mild reaction conditions,can be compatible with a variety of functional groups,broadens the application range of ethyl difluorodioacetate/α-iododifluoroacetamide,promotes the development of cyclopropene radical reaction and provided a new strategy for the synthesis of polyfunctional cyclopropane derivatives.