Cobalt-catalyzed Reaction Of Bromine Monofluorinated Blocks With Alkynes

Based on the special properties of fluorine atoms,the introduction of fluorine or fluorine-containing groups into organic compounds can significantly change their physicochemical and biological activities.Fluorinated organic compounds are widely used in the pharmaceutical,materials and new energy industry,etc.Therefore,the introduction of fluorine atoms or fluorine-containing group into compounds has always been a research hotspot.In the past few decades,significant progress has been made in trifluoroalkylation and difluoroalkylation reactions.However,there are few studies on monofluoroalkylation to synthesize a variety of fluorine-containing compounds.With the increase in the proportion of monofluorinated drugs in the market,the research of monofluorinated compounds has attracted widespread attention.In this paper,we studied the radical addition reaction of bromine monofluoroalkylating reagent with alkynes under the catalysis of transition metal cobalt to obtain a series of monofluorocarbonyl substituted olefin compounds.The first part introduces the radical addition reaction of cobalt-catalyzed ?,?-fluorobromoketones and alkynes to synthesize a series of monofluorocarbonyl substituted olefins.A series of ?,?-fluorobromoketone building blocks with various structures were designed and synthesized using methyl ketone as raw materials,and the radical addition reaction of the building block with terminal alkynes were studied,and 9 monofluorocarbonyl substituted olefin compounds with novel structures were synthesized.In the second part,based on the previous experiments,we explored the addition reaction between ethyl monofluoroalkylation reagent ethyl bromoacetate and alkyne substrates under the cobalt catalyst system.Under the optimal conditions,ethyl monofluorobromoacetate and different alkynes were used to expand the substrate.The study showed that this method is not only suitable for aromatic terminal alkynes,but also suitable for aliphatic and intramolecular alkynes.