C-H/N-H Cross-Coupling And C-O Cleavage Reaction Via N-Centered Radical

Synthetic chemistry contributes to the development of modern society,in the areas that ranging from material,medicine,pesticide and biological.Based on the unique physiological activity,the construction of C-N bonds has attracted much attention from synthetic chemists.It is of great significance to develop efficient,green,and mild amination reactions to build C-N bonds for the synthesis of high-value molecules.In recent years,the chemistry that N-centered radcial as intermediate has provided a new idea for C-H amination and other functionalization reaction.This paper summarizes the development process of transition-metal catalyzed C-H amination reaction in recent years.Then,according to the activation mode,the representative works of amination reaction related to N-centered radcial are introduced,including metals-induced,photo-induced,and electro-induced.The research content of this paper includes the synthesis of aniline derivatives and allylamine derivatives using N-centered radicals as intermediates,starting from the mechanism of the single electron transfer reaction between copper and amines.In addition,using N-centered radcial cation as intermediates,the cleavage of C(sp³)-H is also realized,which further promoted the cleavage of C(sp³)-O bond.The main research results are as follows:1.In this paper,the combination of QXAFS and EPR was applied to study the single-electron transfer progress between Cu(?)and amines,accompanying with the generating of N-centered radcial cation.By Q-XAFS,we can in-situ observe the structural changes and valence changes of copper when the electron transfer occurs.In QXAFS studies,we found that the electron transfer progress between copper and tributylamine is the rate-determining step via tetraamine copper intermediate.By EPR,we directly observed the disappearance of Cu(?),and also proved the existence of a variety of aniline and alkylamine radical cations.This mechanism study provides guidance for our follow-up synthesis of triphenylamine derivatives.2.Using pyrazole radicals as intermediates,which generated by K₂S₂O₈-induced,we have achieved the azolation of phenol derivatives under inexpensive reaction conditions without catalysts.And this strategy can be extended to dia-azolation reaction.Mechanism studies have shown that the activation of phenol may involve the rate-determining step.3.Using amine radical cations as intermediates,which generated by photo-induced,we have realiazed the oxidative amination reaction of unactived olefins to synthesis alkyl allylamines.Combining photocatalyst[Ir(d FCF₃ppy)₂dtbpy]PF₆ and cobaloximes catalyst[Co(dmg H₂)Py₂]PF_6,this strategy is suitable for a variety of alkylamines,and presents unique site selectivity in the amination of natural terpenes.XAFS experiments show that in the initial step,olefins and amines do not affect the activity of the cobalt catalyst.The EPR studies proved that the amine was first oxidized by the excited-photocatalyst to produce amine radical cations,which then added with olefins to produce C-centered radical intermediates.The target product can be obtained smoothly by using sunlight as the light source.4.Using amine radical cations as intermediates,which generated by photo-induced,we have constructed aminated limonene derivatives using pinene as a substrate through remote C(sp³)-H desaturation.This strategy is applicable to a variety of secondary alkylamine substrates,the optical rotation of the substrate can be retained.And according to different positions of double bond in different pinenes,site-selective aminated limonene derivatives can be constructed.DFT calculation provides strong support for the mechanism of this reaction.5.In this paper,we have used the hydrogen-atom transfer ability of N-centered radicals to promote the cleavage of C(sp³)-H bond,realizing a photocatalytic C(sp³)-O cleavage reaction under metal-free conditions.Radical inibition experiments showed that the reaction had undergone a radical process,and isotope labeling experiments proved that the oxygen atoms in the product originated from the substrate itself,not from water.The ¹⁹FNMR experiment proved that there is a single electron transfer process between Selectfluor and the excited state photocatalyst.