Application Of Radical Addition/Cyclization Tandem Reaction In The Synthesis Of Heterocyclic Compounds

Heterocyclic compounds are widely found in natural products and drug molecules,especially five-membered heterocycles,such as pyrrole rings are particularly common in natural products and drug molecules.Therefore,efficient and green construction of five-membered heterocycles is not only useful for drug development,but it also has a certain significance in the academic field.On the basis of reading a large number of domestic and foreign literature,combined with the research direction of our group,this article introduces the cyclization and bifunctionalization reaction of 1,6-enyne based on the free radical process,and efficiently constructs a series of five-membered nitrogen-containing or all-carbon cyclic compounds which furnish difluoromethyl group(-CF2R),alkenyl C-Br,alkenyl C-I and nitro.1.Copper catalyzed atom transfer radical cyclization(ATRC)using of 1,6-enyne and 2-bromo-2,2-difluoroacetate,accessing to a series of five-membered heterocyclic compounds was described,Z configuration of the vinyl C-Br and CF2CO2Et containing cycles were obtained.The structure of all new compounds were characterized by IR,1H NMR,13C NMR,19F NMR,HRMS and other means,and the configuration of the products was determined by X-Ray single crystal diffraction.2.A copper catalyzed bromodifluoroacetylative cyclization reaction has been developed.The treatment of bromodifluoroacete derivatives by CuI and B2Pin2 enables the difluoroalkyl radical generation and to trigger the radical addition/cyclization/bromination sequences.Bromodifluoroacetyl derived amide and ketone were found compatible,delivering the desired five-membered heterocycles which has valuable vinyl C-Br bonds and CF2COR structural units in good yields.The structure of the isolated new compounds were characterized by IR,1H NMR,13C NMR,19F NMR,HRMS and other means.3.Metal free and additive free catalyzed 1,6-enyne,iodoform,and tert-butyl nitrite(TBN)reacted to afford a series of five-membered heterocycles containing precious vinyl C-I and nitro structure units in nitrogen atmosphere.The new compounds were further furnished by cross-coupling.The structure of the synthesized new compounds were characterized by IR,1H NMR,13C NMR,19F NMR,HRMS and other means,and the configuration of the model product was determined by X-Ray single crystal diffraction.In conclusion,this methodology is simple to operate,green and efficient,and has strong substrate compatibility.