The Application Of C-H Bond Functionalization In The Synthesis Of Glycine And Quinoline Derivatives

The C-H bond functionalization is a useful method which would directly introduce the functional groups on the activated C-H bond,and has been widely used in the construction of C-X?X=C,N,S,O,etc.?bonds in recent years.The direct functionalization of the C-H bond enables one-step synthesis of the target molecule,avoids pre-functionalization of the substrate,simplifies the reaction steps,and has high atomic economy.The application of C-H functionalization on the construction of the lead skeleton of active intermediates,the synthesis of compounds with diverse activities or drug potential compounds,which have great importance in the research field of medicinal chemistry.Aryl glycine and aminoquinoline derivatives which have good pharmacological activities were widely existed in natural products and drugs.The directly introduction of reactive groups in glycine and quinoline nucleus by C-H bond functionalization is the simplest and most efficient method for the preparation of glycine and quinolin derivatives.In this paper,we have developed two methods of C-N and C-C bond construction which were applied to the synthesis of aryl glycine and aminoquinoline derivatives.Main parts are as follows:The first chapter briefly introduced the research overview of C-H functionalization reaction in recent years and emphasizes on it's application in C-H functionalization of N-arylglycine derivatives and 8-acylaminoquinoline derivatives in the construction of C-C/C-X?X=C,N,S,O,etc.?bonds;Briefly described the pharmacological activities and synthetic values of N-phenylglycine derivatives and8-acylaminoquinolines,and provided the basis for this topic.The second chapter reported an oxidative coupling reaction between N-aryl glycine esters and acylated amines by copper catalysis using O₂ as an oxidant and CuCl as a catalyst in 50°C for 24 h,providing a novel method for the synthesis of?-amide substituted glycine derivatives.Besides,a variety of N-aryl glycine esters with the different electronic effects of the substituents on the benzene ring could be tolerated by this procedure which proceeds smoothly by reaction with various acylated amines and gives the corresponding product in a moderate to excellent yield?up to 86%?.In the third chapter,a rapidly and efficiently the coupling reaction was achieved for the 8-acylaminoquinoline with difluoroalkyl compounds by using fac-Ir?ppy?₃ as a photocatalyst,DMAP as an additional base in room temperature and blue light.A novel method for the C?sp²?-C?sp³?bond constructing has been developed,and a series of difluoroalkyl-substituted 8-acylaminoquinoline derivatives have been synthesized in moderate to excellent yields?up to 85%?.This protocol owned advantages such as extensive substrate tolerance,excellent regioselectivity?reaction always happened on C-5 position of 8-acylaminoquinoline?,mild conditions and high atomic economy.