Visible-Light-Promoted Direct C3-Perfluoroalkylation Of Imidazo[1,2-α]Pyridine

Due to its special molecular skeleton structure,imidazo[1,2-α]pyridines and their derivatives have found a wide range of applications in the area of medicinal chemistry,material science and organic synthesis.Particularly,C3-functionalized imidazo[1,2-α]pyridines exhibit strong pharmaceutical activities,such as antiviral,antiviral and antiviral properties.At present,imidazo[1,2-α]pyridine is the core structure of several commercially available drug molecules including Zolpidem,Saripidem,Alpidem and Necopidem,etc.Because of their importance and broad applications,to further find more bioactive molecules,an increasing number of scientific researchers are committed to modifying the nature of imidazo[1,2-α]pyridines.Therefore,the development of synthesiz ing various C3-substituted imidazo[1,2-α]pyridine derivatives with green,safe and direct methods has become a popular research topic.This article mainly describes a straightforward approach for the visible-light-induced C3-perfluoroalkylation of imidazo[1,2-α]pyridines by using imidazo[1,2-α]pyridines and perfluoroalkyl iodides as substrates in the absence of any transition-metal catalyst,oxidant and photocatalyst.Mechanistic work suggested that the reaction was a free radical reaction initiated by EDA complex.The main contents of this thesis are as follows:（1）The C3-functionalization reaction of imidazo[1,2-α]pyridines and the perfluoroalkylation reaction involving EDA complex were briefly summarized,and the background,significance and research plan of this paper were introduced,respectively.（2）The method of synthesizing 3-perfluoroalkyl imidazo[1,2-α]pyridines from imidazo[1,2-α]pyridines and perfluoroalkyl iodides promoted by an EDA complex under visible light was studied.By exploring the effects of illumination time,bases,solvents and gas environment on the reaction,the optimal conditions were obtai ned,and the scope of substrates was examined under these conditions.（3）According to the relevant literature and a series of mechanism experiments,a plausible mechanism of the reaction was proposed.First,DBU forms an EDA complex with perfluoroalkyl iodides.Under the irradiation of visible light,the EDA complex is activated to the excited state,which then dissociates into the R_f·radical,iodide anion,and radical cation DBU^+·.Subsequently,the R_f·radical attacks the C3-position of imidazo[1,2-α]pyridine by coupling reaction,and the generated intermediate is oxidized to form a cationic intermediate.Finally,by deprotonation of cationic intermediate affords C3-perfluoroalkyl-substituted imidazo[1,2-α]pyridine（path a）.Alternatively,abstraction of a hydrogen atom from 3-perfluoroalkyl imidazo[1,2-α]pyridine radical by the iodine radical,which is formed in situ from radical cation DBU^+·and iodide,is also possible to give the target product（path b）.