| Carboxylic acids are an attractive source of carbon because of their abundance in nature and their low cost.The development of methods for the construction of amines and their derivatives based on the decarboxylation of carboxylic acids is of great economic and synthetic value.Amines are commonly found in natural products and biologically active molecules and are used in a wide range of applications including pharmaceuticals,dyes and materials.Therefore,the preparation of amines by decarboxylative amination of carboxylic acids would be a strategic approach with low cost,high quality and significant impact.In the first chapter of this paper,the research progress on decarboxylation of carboxylic acids to construct C-N bonds was mainly introduced,and dioxazolone,a commonly used amidation reagent in recent years,was also introduced.In Chapter 2,we developed a new method for the decarboxylation of dicarboxylic acid and dioxazolone via base mediation.Through optimization of reaction conditions,it was found that under the action of 1,8-Diazabicyclo [5.4.0] undecane-7-ene(DBU),the reaction yield of ibuprofen and methyl dioxazolone was as high as 97%.At the same time,compatibility inspection showed that this method could be effectively compatible with benzyl carboxylic acid,ordinary secondary alkyl carboxylic acid,aryl carboxylic acid and primary carboxylic acid derived dioxazolone.In Chapter 3,a series of application studies and mechanistic investigations are carried out.Several carboxylic acid drug molecules were successfully converted into amide compounds by this reaction,which provides a method for the derivatization of carboxylic acid active molecules.In addition,we investigated the stereoselectivity of this method using chiral carboxylic acids as substrates and found that carboxylic acid chirality can be effectively retained,generating corresponding chiral amine compounds with an ee value higher than 90%.The above exploration demonstrates the synthetic value of reactions.Through mechanism experiments such as by-product monitoring,free radical capture,and intermediate synthesis,we explored the mechanism of this novel reaction and proposed a multiple rearrangement reaction path.And the rationality of the mechanism was confirmed through intermediate validation experiments.In this paper,a novel method for decarboxylative C-N coupling was developed.The method has mild conditions,simple system,green and high efficiency,and does not require the use of metal reagents.It can provide new ideas and methods for the conversion and application of carboxylic acids and the synthesis of amine compounds. |
