Visible Light-Mediated C3 Functionalization Of Imidazo[1,2-α]Pyridine

Imidazo[1,2-α]pyridines and their derivatives are a class of important nitrogen-containing heterocyclic compounds,which exist in many pharmaceutically active molecules,natural products and function al materials.Moreover,imidazo[1,2-α]pyridines have a wide range of biological and pharmaceutical properties,such as anti-cancer,antiviral,antibacterial,anti-inflammatory,and antiprotozoal properties.For example,C3-substituted imidazo[1,2-α]pyridine is the main skeleton component of several commercially available drugs,such as salipitant,alpitant,minodronic acid,nopidine,zolpidem,etc.In addition,different C3 substituents can have significant effects on their bioactivities.Due to these interesting properties and applications,the direct functionalization of the C-H bond at the C3 position of imidazolo[1,2-α]pyridine has attracted extensive attention of researchers.Despite great advances in thi s field,the development of new and simple methods to constru ct structurally diverse imidazo[1,2-α]pyridines is still highly desirable.In thi s paper,C3-substituted imidazo[1,2-α]pyridines were synthesized by free radical under visible light irradiation using ruthenium as photosensitizer,based process from imidazo[1,2-α]pyridines and diazo compounds.The main contents of this thesis are as follows:（1）Free radical coupling reaction at C3 position of imidazo[1,2-α]pyridines and the synthesis method of Zolpidem,a commercially available drug,are briefly summarized,and the background,significance and research plan of this thesis are introduced.（2）The photocatalytic reaction of imidazo[1,2-α]pyridines with diazo compounds to synthesize C3-substituted imidazo[1,2-α]pyridine compounds was studied.The optimum conditions of the reaction were explored through the influences of the types and dosages of photosensitizers,the types of additives,solvents,light source and gas environment,and the range of substrates was expanded under the optimized conditions.（3）Based on the relevant literature and mechanism experiments,a reasonable mechanism of the reaction was proposed.Initially,Ru（bpy）₃²⁺is transformed to its excited-state*Ru（bpy）₃²⁺under visible light irradiation,then diazo compounds interacts with the excited photocatalyst to afford the alkyl radicals and Ru（bpy）₃³⁺via single-electron reduction.Then,the alkyl radical attacks at the C-3 position of imidazo[1,2-α]pyridine and the generated radical intermediate is oxidized by Ru（bpy）₃³⁺to give a cationic intermediate.Finally deprotonation of the cationic intermediate gives the desired C3-substituted imidazo[1,2-α]pyridines.（4）The potential application value of this reaction was demonstrated by gram scale amplification and further modification of imidazol o[1,2-α]pyridine derivatives.