Visible-Light-Mediated Direct C-H Perfluoroalkylation Of Imidazopyridines

The perfluoroalkyl substituents are important structural units,which can be found in many compounds used in medicinal chemistry,agrochemistry and material science.The incorporation of perfluoroalkyl groups into organic molecular could change their physical and biochemical properties.In this thesis,visible-light-promoted direct C-H perfluoroalkylation of imidazopyridines with perfluoroalkyl iodide was developed.This transformation does not require photoredox catalyst and proceeds smoothly under mild conditions to give the desire product in moderate to excellent yields.It provided a green and simple alternative approach for the synthesis of perfluoroalkylated imidazoheterocycles.1.A series of imidazopyridines were synthesized from 2-aminoheteroarenes by using different methods to afford the starting materals for the perfluoroalkylation of imidazopyridines(Scheme 1).2.The model reaction of 2-phenylimidazo-[1,2-a]pyridine and perfluorobutyl iodide was studied by optimizing the solvent,base and other conditions.The optimal reaction conditions were obtained as the combination of 1.0 equiv(0.2 mmol)2phenylimidazo-[1,2-a]pyridine,2.0 equiv perfluorobutyl iodide,2.5 equiv DBU as base,DMSO as solvent at room temperature under blue light irradiation for 12 h.The corresponding product was obtained in 83%isolated yield(Scheme 2).3.Under the optimized reaction conditions,a series of imidazohetercycles and perfluoroalkyl ioides were investigated.Mild reaction conditions,not using photoredox catalyst and broad substrate scope were the considerable advantages of this methodology.The control experiments indicated that a perfluorobutyl radical was involved in the reaction.The UV/Vis absorption spectra of a mixture of perfluorobutyl iodide and Lewis base indicated the formation of an electron donor-acceptor(EDA)complex.The strategy would be helpful for the drug development of imidazo[1,2a]pyridines,and it is expected to get the applications in drug synthesis(Scheme 3).