Manganese-Catalyzed/Mediated Radical 6-endo-trig Cyclization Of Isocyanides To Access 4-CF₃-Quinoline Derivatives

Quinolines are one of the most important N-heterocyclic aromatic compounds,which have a wide range of applications in the field of biology and material science.The incorporation of trifluoromethyl group into quinoline might further improve its physiological and pharmacological properties.In this thesis,we studied the radical cyclization of 1-isocyano2-[1-(trifluoromethyl)ethenyl]benzene to efficiently construct 2substituted 4-trifluoromethylquinoline derivatives by using different radical sources.This thesis includes the following three parts:The first chapter mainly introduces the properties,preparation and synthetic application of isocyanides.It also details the methods for the synthesis of quinolines and biologic activities of quinoline compounds.In the second chapter,various 4-trifluoromethyl-2-phosphinoyl quinolines have been synthesized by direct radical 6-endo-trig cyclization of 1-isocyano-2-[1-(trifluoromethyl)ethenyl]benzenes with diarylphos phine oxides using catalytic manganese acetylacetone without any external oxidant,ligand or additive.A reasonable reaction mechanism of Mn(Ⅲ)/Mn(Ⅱ)catalytic cycle was proposed.In the third chapter,a series of 4-trifluoromethyl-2-arylquinoline compounds were prepared with moderate to good yields through the radical cyclization reaction of 1-isocyano-2-[1-(trifluoromethyl)ethenyl]benzenes and aryl boric acids under the mediation of manganese acetylacetone.In conclusion,a variety of 4-trifluoromethyl-2-functionalized quinoline derivatives have been effectively synthesized,which provides an useful method for the synthesis of related drugs in the future.