Studies Of Transition-Metal-Catalyzed C-H Functionalization Reaction Of Glycine Derivatives

The functionalization of carbon-hydrogen bonds has always been of great significance in organic synthetic chemistry.It is an efficient and concise synthesis strategy for constructing C-C bonds and C-heteroatom bonds.In recent years,the functionalization of C-H bonds has developed rapidly.After Li Chao-jun proposed the concept of cross-dehydrogenation-coupling,it attracted great attention from chemists.Various kinds of cross-dehydrogenative-coupling reactions have been reported.α-Amino acids are the core skeleton of proteins,which are widely found in natural products and drug molecules and play an extremely important role in human life.It is a very useful module in organic synthesis.Theα-C(sp~3)-H bond functionalization of glycine derivatives has important research value.The transition-metal-catalyzed glycine derivatives can be cross-coupled with other organic reagents byα-C(sp~3)-H bond activation to directly and efficiently synthesizeα-substitutedα-amino acid derivatives.A variety ofα-amino acid derivatives can be synthesized by selecting and controlling the diversity of reaction substrates.This provides important research ideas for biochemistry,medicinal chemistry,and synthetic chemistry.In this paper,the activation ofα-C(sp~3)-H bond of glycine derivatives was introduced,and the related progress was introduced.The cross-dehydrogenative-coupling reaction of glycine derivatives was also studied.The first chapter summarizes the research progress ofα-C(sp~3)-H bond functionalization reaction of glycine compounds.Firstly,the formation ofαposition C-C bond of glycine derivatives is introduced,includingα-alkylation,α-arylation,andα-alkynylation.Secondly,the formation ofα-position C-heteroatomic bonds ofα-amino acid derivatives is introduced,including the formation of C-P bond,the formation of C-N bond,the formation of C-O bond and the formation of C-S bond.There are also oxidation tandem/cyclization reactions in which glycine derivatives are involved.In the second chapter,a rapid and highly efficient copper(II)-catalyzed cross-dehydrogenative-couplingreactionofN-arylglycineesterswith imidazo[1,2-a]pyridines has been described.The use of copper salt as a catalyst and air as the terminal oxidant makes this transformation sustainable and practical.A broad range of N-arylglycine esters underwent the cross-dehydrogenative-coupling reaction smoothly wtih2-arylimidazo[1,2-a]pyridines to giveα-substitutedα-amino acid esters in excellent yields.This synthetic method has the advantages of high yields,good functional groups compatibility,simple operation,and mild reaction conditions.A possible mechanism for the cross-dehydrogenative-coupling reaction is also proposed.In the third chapter,a simple and highly efficient cross-dehydrogenative-coupling reaction between N-aryl glycine esters and imides or amides by the catalysis of a copper salt without the requirement of peroxide agents is described.The novel reaction provides a facile approach for the synthesis ofα-substitutedα-amino acid esters through C-H/N-H oxidative cross-coupling.This synthetic approach has the advantages of good yields,simple operation and mild reaction conditions.In the fourth chapter,a novel and efficient direct oxidative phosphonylation ofα-amino ketones andα-amino acid derivatives with dialkyl phosphites by the catalysis of a cobalt salt under air was disclosed.A variety ofα-amino ketones andα-amino acid derivatives underwent the reaction well with dialkyl phosphites to produce the desiredα-aminophosphonates.This method which provides another synthetic way for the preparation of a variety ofα-aminophosphonyl derivatives is sustainable and practical by using inexpensive cobalt salt as catalyst and air as green oxidant.