Study On Carboxyl Group Assisted Ortho-C（sp²）-H Acetoxylation Of Hydrocinnamic And Phenylacetic Acids And NH₂-Directed Phenethylamine Ortho-C（sp²）-H Iodination

In recent years,aromatic carboxylic acids and aliphatic amines have played an important role in medicine and agrochemicals,so the C-H activation of aromatic carboxylic acids and aliphatic amines catalyzed by transition metals has received extensive attention.To achieve high site selectivity for C–H activation,a strategy of introducing suitable auxiliary directing groups is usually adopted.In the absence of any external directing group,the realization of a highly site-selective C-H activation reaction through the directing group of the substrate itself will make the atoms and steps more economical.This paper mainly discusses the palladium-catalyzed carboxyl-directed ortho-C(sp~2)acetoxylation of hydrocinnamic acid and phenylacetic acid,and the palladium-catalyzed ortho-C(sp~2)-H iodination of free amine-directed phenethylamine.Research.The main research contents are as follows:In the first part of the work,the first case of palladium-catalyzed carboxyl group-directed ortho-C(sp~2)-H oxidation reaction of hydrocinnamic acid was realized by using the carboxyl group of the substrate itself.It is generally believed that the seven-membered ring palladium intermediate of hydrocinnamic acid is not conducive to the C(sp~2)-H activation reaction,but this reaction successfully overcomes the above difficulties and expands the rich substrate.Subsequently,the ortho-C(sp~2)-H acetoxylation of phenylacetic acid was realized,and the substrate adaptability was great.This reaction enables the diversification of the drug molecules Ibuprofen,Ketoprofen and Flurbiprofen.The acetoxy group of the product easily reacts to a hydroxyl group,which can be further transformed into other useful derivatives.In the second part of the work,a palladium-catalyzed amine group-directed ortho C(sp~2)-H iodination reaction of phenethylamine was realized by using the amine group of phenethylamine.The reaction does not require additional directing groups,reflecting higher atom economy and step economy.The reaction is characterized by mild conditions and high site selectivity.Some substrates have been expanded and yields are good.It is promising to expand more abundant substrates in subsequent processes,and the resulting iodinated products have the potential to be converted into more useful molecules.