Photoredox Amine-alkyl Radicls Participate In The Synthesis Of Chiral And Complex Aza-aromatic Derivatives

Stereochemistry plays a vital role in medicinal chemistry,biochemistry,agrochemistry,and materials chemistry and other subjects..Therefore,it is particularly important to design an effective method to prepare a single enantiomer of a chiral compound.Asymmetric catalysis is devoted to the development of chiral catalysts which can convert prochiral and racemic substrates into valuable chiral precursor.Since the first report in the 1960 s,a large number of chiral organometallic complexes and small organic catalysts have been used for asymmetric catalysis,and a good catalytic effect has been achieved.Therefore,the 2001 Nobel Prize in Chemistry was awarded to three pioneers in the field of asymmetric catalysis by William S.Knowles,RoyojiNoyori and K.Barry Sharpless in recognition of their outstanding contributions to the development of catalytic asymmetric synthesis.Nitrogen-containing aromatic heterocyclic compounds widely exist in natural products and pharmaceutically active molecules.Therefore,the direct construction of aromatic heterocyclic compounds by simple and effective methods has always been a concern of researchers.Nitrogen-containing aromatic heterocyclic compounds such as quinoline,isoquinoline and pyridine are more difficult to construct in chiral centers than carbonyl compounds due to their unique chemical properties.With the first proposal of the 1971 Minisci reaction concept,the alkylation of nitrogen-containing heterocyclic aromatic hydrocarbons by Bronsted acid-activated radical addition is possible to realize chiral construction.In recent years,the conversion of light energy into chemical energy by visible light-induced single electron transfer has realized the green construction of compounds.And the realization of chiral compounds through the combination of visible light induction and asymmetric catalysis has attracted people’s attention and become a hot point.Based on the original asymmetric catalysis of organic small molecules,our group developed a synergistic catalytic mode combining visible light catalysis with chiral Bronsted acid using the organic photosensitizer DPZ as the medium.It is the first time to achieve the asymmetric Minisci reaction which the isoquinoline was its substrate andprovides a highly efficient,green dual catalytic system for the synthesis of chiral nitrogen-containing aromatic heterocyclic compounds,and has made some very good progress.On this basis,We have raised the following questions:1.Visible light induced asymmetric amine alkylation of isoquinoline(minisci-type reaction)Since the concept of the Minisci reaction,the use of brφnsted acid activation to directly construct aromatic heterocyclic alpha-asymmetric amine alkylation by free radical addition has not been reported so far,we have used amino acid-derived Activated esters(RAEs)and isoquinolines are used as raw materials.The asymmetric amine alkylation reaction of isoquinoline as substrate is realized for the first time by using chiral brφnsted acid and photocatalytic dual catalytic system,thus constructing a series of very valuable Isoquinoline substituted chiral secondary amine.2.Construction of nitrogen-containing seven-membered bridged ring compound by free radical addition of isoquinoline oxynitrideOn the basis of the previous work,in order to further explore the properties of aromatic heterocycles,we used isoquinoline oxynitride and nitrogen phenylglycine as raw materials to successfully realize one-step construction of seven-membered nitrogen-containing bridged ring compound(decane derivative)under photoredoxand alkaline conditions.And the successful synthesis of seven-membered bridged ring compounds with multi-molecular amine alkyl radicals under conditions of only changing solvents and bases,provide a synthesis of complex aromatic heterocyclic compounds.in accordance with.