Palladium-Catalyzed C-H Activation For The Synthesis Of Unnatural ?-amino Acid Derivatives

In recent years,C-H activation methodology which achieved a breakthrough has become a hot topic in organic chemistry.The formation of C-C,C-X(X = O,N,Br or other hetero atoms)bond via straightforward transformations of C-H bond is recognized as one of the most efficient and environmental friendly methods in the organic synthesis area.It's of certain academic significance and practical value to develop efficient and novel transition metal-catalyzed C-H activation methods for the synthesis of unique structural motifs.On the other hand,amino acids,as one of the most important structural skeleton,are widely existing in the nature and have drawn wide attention due to their unique bioactivity.Amino acids are not only identified as the basic building blocks of proteins and peptides,but also commonly used in the fields of medicine,food,cosmetics and materials.With the rapid development of pharmaceutical chemistry,more and more small biologically active molecules such as amino acids,peptides,monoclonal antibodies,have been used in medical treatment or food industry.Amino acids have a broad range of applications,while due to the limited number of genetically coded amino acids,the exploration of an efficient method in the modification of amino acids becomes an urgent need.With the academic background of transition-metal catalyzed C-H activation and the target of amino acids derivatives,we chose ?-phenylglycine where is few research on as the substrate.Pd-catalyzed o-C-H functionalization of phenylglycine and 4-hydroxyphenylglycine using picolinamide as a directing group is reported.We have developed different protocols for the alkoxylation,acyloxylation,halogenation,arylation and alkynylation of these substrates.These reactions exhibit high selectivity,broad substrate scope,and compatibility with different functional groups with moderate to high yields.They provide a rapid and efficient access to a variety of phenyl based amino acid derivatives which can be further modified and have broad spectrum of applications in medicinal chemistry.