Investigation On The Construction Of C(=O)-C(sp~2)bond And C(=O)-N Bond Via Electrochemical Decarboxylative Coupling Of Glyoxylic Acid

Electro-organic synthesis uses electrons as a“clean”reagent to replace traditional redox agents,which can reduce the waste generated by chemical reagents in conventional synthetic methods,and is thus a recognized green method.Electro-organic synthesis can be divided into direct electrolysis and indirect electrolysis.Under direct electrolysis,the reaction substrates or intermediates undergo electron transfers with the electrodes,while under indirect electrolysis,mediators?or redox catalysts?can be used that undergo heterogeneous electron transfers with the electrode surface to form the stabilized intermediates which can then oxidize or reduce the substrate molecules homogeneously.Due to the mild conditions,high selectivity,and sustainability,electro-organic synthesis has become a hot topic in the field of organic synthesis in recent years,and numerous new reactions and new synthetic strategies have been developed by means of electro-organic synthesis.Decarboxylative coupling of carboxylic acid is a common strategy to construct new chemical bonds in organic synthesis.As a classic electrochemical reaction,Kolbe reaction has been popular since its discovery in the 19th century.After two centuries of development,the use of electrochemical methods for decarboxylative coupling reaction has become an important method for constructing carbon-carbon and carbon-hetero bonds.Glyoxylic acid is a very common C2 carboxylic acid.However,using glyoxylic acid as the C1 synthon via decarboxylative coupling is seldom reported.Moreover,no research on the electrochemical decarboxylation of glyoxylic acid has been disclosed.In this paper,the electrochemical strategy is used to study the electrochemical decarboxylation coupling reaction of glyoxylic acid,which realized the construction of C?=O?-C?sp²?and C?=O?-N bonds.The thesis includes mainly the following two parts:The second chapter studies on the method of electrochemical decarboxylative coupling of glyoxylic acid with indoles under the catalysis of amine to construct C?=O?-C?sp²?bonds.In this reaction,dimethylamine or aniline serves as a dual functional catalyst,which not only lowers the decarboxylation energy barrier of glyoxylic acid,but also activates the formyl group towards the nucleophilic reaction.The catalytic loading can be as low as 1 mol%when the dimethylamine is used.This reaction shows a wide range of substrate scope.It is suitable for both electron-poor and electron-rich indole rings,which could be N-substituted or free.The mechanistic studies show that glyoxylic acid condenses with the amino-catalyst to form an imino acid intermediate,followed by the decarboxylation,attack of indoles,and finally affords the product.The method utilizes cheap raw materials with simple operation,and provides a new strategy for the synthesis of 3-formylindoles.The third chapter studies on the method of electrochemical decarboxylative coupling of glyoxylic acid with amines to construct C?=O?-N bonds.The reaction,which uses Cu?OAc?₂?H₂O as an electrocatalyst,Ni Cl₂?6H₂O as a Lewis acid,and cesium carbonate as a base,is performed under ambient conditions with simple operation.It shows strong functional group compatibility.The mechanistic experiments show that glyoxylic acid first condenses with the amine to form an imino acid intermediate,and then undergoes a Hofer-Moest decarboxylation to generate a carbocation,which reacts with water to generate the final N-formamides product.