Synthesis Of Quinolines Derivatives Via Transition Metal-Catalyzed Cascade Annulation Reaction

Because of its good biological activity and pharmacological activity, quinolines derivatives are not only widely exist in the natural products, but also widely used in the field of medicine, pesticide, etc. In recent decades, the synthesis of quinolines derivatives are also gradually developed. The early method mainly based on the non-metal catalytic method, but at the moment the method with the characteristics of fast, simple and efficient, which is based on transition metal catalytic tandem cyclization reaction is dominanting.As an important kind of class of organic molecules, isocyanides are known to take part in a rich array of different types of reaction, with particular usefulness in a wide variety of multi-component reactions. Isocyanides differ from nitriles in that the other structure is bound to the rest of the molecule through nitrogen as opposed to carbon. This gives the isocyanide an almost unique set of properties, shared only with carbon monoxide and carbenes, in that they can react with the same carbon atom both nucleophiles and electrophiles.Therefore, we proposed to realize the synthesis of quinolines derivatives via insertion of isocyanide or metal carbene. The thesis is divided into five parts altogether.The first chapter, mainly summarized the important application value of quinolines derivatives in drug molecule, some classic methods for the synthesis of quinolines derivatives, and the different types of reactions isocyanide involved.The second chapter reported a method for the synthesis of a series of 2-trifluoromethyl quinolines derivatives with potential bioactivities under the catalysis of transition metal palladium by the insertion of aryl iodine and isocyanide and the intramolecular cyclization, this method provides a new route for the synthesis of quinolines derivatives.The third chapter expounds the implementation of the construction of double C-C bond and the cyclization reaction under the transition metal palladium catalyst by the method of C-H activation and the insertion of different isocyanides. We synthesized a number of 2-trifluoromethyl-4-amino-quinoline derivatives in moderate to good yields under the copper acetate as the oxidant.Thesis in the fourth chapter introduced the construction of C-N and C-C bonds by tandem cyclization reactions catalyed by palladium. The reaction has synthesized a tremendous amount of 2-amino quinolines derivatives with potential pharmacologically activity by taking aniline adjacent alkenyl and tert-butyl isocyanide as starting materials and choosing DBU as the base.The fifth chapter introduces the synthesis of a great deal of 2-ester quinoline derivatives by the construction of C-N bond and the implementation of the C-H activition through the diazonium in the form of metal carbene under the condition of rhodium as the catalyst and copper acetate as the oxidant and sodium carbonate as the base.In summary, we have synthesized a series of functionalized quinolines derivatives via tandem cyclization reaction involving the insertion of isocyanides and diazonium under the action of transition metal, this kind of compounds has potential applications in medicine and pesticide.