Copper-catalyzed Tandem Cyclization Of 2-ene/Alkynylaniline With Glyoxylic Acid

Heterocyclic compounds widely exist in nature and play an important role in the physiological activities of animals and plants.For a century,the synthesis and application of quinoline and indole compounds has been a key field of heterocyclic chemistry,and has been favored by many chemical workers.Developing a faster,environmentally friendly and efficient route to construct indole and quinoline compounds has been one of the goals pursued by scientists.Quinoline and indole derivatives play an important role in the production of medicines,pesticides and chemicals.For example,tryptophan,an indole derivative,is an amino acid necessary for human nutrition,which can cure symptoms such as insomnia and headache.Therefore,this thesis introduces the progress in the synthesis of indole and quinoline compounds,and also develops new methods for the synthesis of quinoline and indole derivatives under the catalysis of transition metal copper salts.The specific content of this thesis is explained from the following aspects.The first chapter firstly summarizes the traditional synthesis methods of Skraup-Doebner-Vonmiller and Friedl?nder,as well as the recent research progress in the synthesis of quinoline derivatives catalyzed by palladium,copper,and other transition metals.Then,the research progress of the traditional synthetic methods for the synthesis of indole derivatives by Bartoli and Fischer,and the transition metals such as copper-,palladium-and rhodium-catalyzed methods are also reviewed.In addition,we also introduced the reactions for the participation of aldonic acid in recent years.The second chapter mainly studies the[5+1]tandem cyclization reaction of2-alkenyl arylamine and glyoxylic acid under the action of copper acetate.A series of important quinoline derivatives are obtained in moderate to good yields.The reaction system may involve the following processes:?1?nucleophilic addition of alkenyl arylamine with glyoxylic acid.?2?releasing a molecule of water to form an imine.?3?6?electron cyclization.?4?decarboxylation and oxidative aromatization.It is worth mentioning that copper salts and air as the terminal oxidant.The reaction features easily available raw materials,good applicability of the substrate,and gram-scale available.The third chapter mainly studies the cyclization reaction of 2-alkynyl arylamines and glyoxylic acid monohydrate in DMSO solvent catalyzed by copper,to provide a series of indolaldehyde derivatives in good yield.The reaction process may involve the following processes:?1?the coordination of Cu?II?with the alkyne bond of alkynylarylamine;?2?releasing a molecule of HX;?3?the formation of indole intermediate via the intramolecular cyclization;?4?the reaction of indole intermediate with glyoxylic acid to provide the target product and releasing a molecule of CO₂.Cu?I?is oxidized by oxygen in the air and to enter the next cycle.The reaction has the characteristics of short reaction time,simple operation,mild conditions,and good substrate applicability.For example,the electron-donating and electron-withdrawing groups,and the heterocyclic ring are compatible.In summary,we developed a series of Cu-catalyzed cyclization reactions of2-alkenyl/alkynylarylamines with glyoxylic acid to give the corresponding quinoline/indole derivatives in good to excellent yields.