Synthesis Of Remote Fluoroalkylated α-Hydrogen/Deuterium Azaarene Derivatives Via 1,n-Hydrogen Atom Transfer Strategy

Nitrogen-containing aromatic heterocylces(azaarenes)are widely found in bioactive pharmaceuticals,pesticides,natural and non-natural product molecular structures.According to statistics,nearly half of the top 200 global best-selling drugs published by the FDA contain nitrogen and heteroaryl structural units.It can be said that "No nitrogen,no medicine".As one of the most popular structural unit,fluoralkyl groups are widely existing in drug molecules or drug intermediates.The combination of azaarenes and fluoroalkyl groups will be potential applications in compound transformation / active molecules modification and drug research and development.Therefore,the efficient and practical building of remote fluorinated azarene is of great significance in real production and life.The research literatures report that the traditional synthesis of fluoroazarene often requiring the modificated azarene substrate and tedious operations.Recently,chemical conversion reactions driven by electron properties of electron-deficient azarenes have provided ideas for the direct synthesis of fluorinated azarenes.Based on our research group’s previous research on visible light catalysis and azarene,this paper takes the organic photosensitizer DPZ independently developed by our research group in the early stage as photocatalyst,and uses the electron deficiency characteristics of azarene such as pyridine and quinoline to directly trigger the reaction to synthesize remote fluorinated azaarene derivatives.The reaction process is mainly as follows: DPZ is excited to excited state by visible light,Langlois reagent is oxidized by excited state photosensitizer to generate fluoralkyl radical and reduced DPZ,and then the fluoralkyl radical is added to the olefin substrate.The nonpolar matched hydrogen atoms transfer to form α-azaarenes radicals,The α-azaarenes radicals are reduced by the reduced photosensitizer to obtain α-azaarenes anions and ground state DPZ,and the α-azaarenes anions capture protons/deuterium to complete the whole cycle.This study efficiently constructs remote fluoroalkyl substitution α-hydrogen / deuterium azaarene derivatives.