Cu-Catalyzed Decarboxylative N-Arylation Of Indole-2-carboxylic Acids

N-aryl indoles are ones of important heterocyclic compounds that show a wide range of biological activities and pharmacological properties.Recent studies have shown that the compounds containing this structural unit have potential applications in inhibiting tumor cell growth,treating cardiovascular diseases and diabetes and so on.There are several methods for the synthesis of N-aryl indoles.Firstly,noble metals such as palladium or rhodium are used as the catalysts.Secondly,inexpensive transition-metal complexes such as copper salts or iron salts are selected as the catalysts.And iron salt and copper salt can also be used together to promote the reaction by synergistic catalysis.Thirdly,the methodology without a transition metal as a catalyst has also been reported.But the reaction often needs to add the equivalent of the promoters with high temperature or microwave irradiation.Owing to their important biological and pharmacological properties,the development of novel synthesis protocols to access N-aryl indole is still highly desirable.In this thesis,a novel synthetic methodology of preparation of N-aryl indoles has been developed by using simple and commercially available indole-2-carboxylic acids and aryl halides as starting materials,and the low-cost and less toxic copper oxide as a catalyst.During the optimization of the reaction conditions,we used the reaction of indole-2-carboxylic acid and iodobenzene as a template reaction,and we tested the effects of copper salts,bases,solvents,reaction time and reaction temperature on the yield of the product.After determining the optimal reaction conditions,we investigated the substrate scope of indole-2-carboxylic acids and aryl halides.The results show that the reaction has good functional group tolerance.We constructed a series of N-aryl indoles with high yields by using the optimal catalytic system.We have developed a simple,inexpensive and efficient method for the synthesis of N-aryl indoles.This method will be expected to promote the study of the pharmacological and biological properties of N-aryl indoles.It will provide an efficient synthetic method for the development of the potential value of N-aryl indoles.