Palladium-catalyzed Site-selective C-H Bond Activation Reaction Of Phenol Derivatives

In the past two decades,transition metal-catalyzed inert C-H bond functionalization reactions have received extensive attention and have become an important branch in the field of organic chemistry research.It shows certain advantages in terms of atomic economy and step economy,conforms to the research concept of green and sustainable development,and has a wide range of applications in synthetic drugs,pesticides and complex natural products.Compared with most common organic synthesis methods,the inert C-H bond functionalization reaction(C-H bond activation reaction)shows certain advantages in the construction of characteristic functional groups for small organic molecules.It no longer needs to go through the steps of pre-functionalizing the raw materials or introducing protective groups.It can be synthesized in one step to directly convert the inert CH bonds in the organic compound into various functional groups required,thereby shortening the synthesis steps and reducing Discharge of organic waste.At present,there are two main types of research on the functionalization of CH bonds.One is to pre-modify the substrate and introduce a guiding group or protecting group,and the other is to use the characteristics of the substrate itself without modifying the substrate..In comparison between the two,the research on the former is close to maturity,especially the regioselectivity of a specific reaction site of the substrate has shown certain advantages;while for the latter,it can There are fewer studies on directly using the unique groups of the substrate to drive the CH bond activation reaction,and the latter can reduce the steps of modifying and deprotecting the substrate.Therefore,the study of new and efficient template substrates without modification is of great significance to the C-H bond activation reaction.This dissertation mainly focuses on transition metal catalysis,and takes the orthoiodination reaction of the C-H bond functionalization reaction as the starting point to carry out the following two aspects of reaction research respectively.1.Use 2-phenylphenol without substrate modification as the reaction substrate,and use an aryl iodide that is cheap and easy to obtain,with mild reaction conditions,and stable properties as a new type of iodination reagent.Use 2-Hydroxy-5-bromopyridine is used as a ligand,and a catalytic amount of silver chloride is used as an additive.Under mild alkaline reaction conditions,the ortho-selective CH bond iodination reaction of 2-phenylphenol catalyzed by palladium is realized.This reaction shows excellent regioselectivity and good functional group tolerance,and the substrates with a series of electron-donating or electron-withdrawing groups on the aromatic ring and the hydroxy aromatic ring can obtain a moderate to good Separation yield.The characteristic of this method is that there is no need to modify the template substrate:a guiding group is constructed or a protective group is inserted,thereby shortening the synthesis steps and reducing waste discharge.It has potential application prospects in synthetic ligands,drug molecular fragments,complex natural products,etc.2.Using phenoxyacetic acid as the template substrate,carboxyl group as the guiding group,using the above-identified aryl iodide as the iodination reagent and N-formylglycine as the amino acid ligand,under mild alkaline conditions and under palladium acetate Under the catalytic action of phenoxyacetic acid,the ortho-selective CH bond iodination reaction of phenoxyacetic acid can be realized.The reaction has a wide range of substrate applications,and the expanded substrate can be reacted at 90 o C for 24 hours or 48 hours to obtain medium to good separation yields.The guiding group of the substrate can be efficiently removed under mild alkaline conditions,and the obtained iodinated product can be used as an intermediate to be converted into other useful derivatives.