Visible-light-catalyzed Deoxygenation And Coupling Reactions Of Pyridyl Ethers

In recent years,the field of visible light redox catalysis has developed rapidly.The preparation of high-value-added chemicals through visible-light-mediated organic synthesis has become an important strategy in the field of synthetic chemistry.At the same time,oxygen-containing compounds are widely available in nature and simple to synthesize,so it is important to study the application of deoxygenation for further transformation.Among them,the cleavage of the C(sp~3)–O bond to generate alkyl radicals for subsequent reactions,is one of the most direct methods to achieve the conversion of oxygen-containing compounds.The visible-light-mediated C(sp~3)–O bond cleavage can achieve generation and conversion of alkyl radicals under mild and green conditions,which opens up a new way for deoxygenation/coupling reactions.In this paper,the recent progress in this field will be reviewed and the work will be carried out on deoxygenation and coupling reactions of pyridyl ethers.The specific research contents are as follows:First of all,we started with benzyl pyridyl ether,which has cheap raw materials and is easy to synthesize.Its redox performance is improved by N-methylation of the pyridine ring into salt.The new C(sp~3)–C(sp~3)bond was successfully constructed by photoredox-catalyzed alkyl radical generation followed by coupling with allyl sulfone.After a series of optimization of reaction conditions,various allylation products were obtained in 19-90%yields.In addition,a simple"one-pot method"was successfully established,eliminating purification of the corresponding pyridinium salts and reducing the reaction steps.Finally,reaction mechanism of this system was explored via a series of chemical,photochemical and electrochemical studies.Based on the above work,this paper further explored the deoxygenation and vinylation of pyridyl ethers.It is worth noting that,in this system,some alkyl radicals underwent homocoupling side reactions.By adjusting the electronegativities of pyridine rings and enhancing the activities of vinyl sulfones via appropriate Lewis acid,a series of styrenes were successfully obtained in 26-66%yields.Furthermore,two possible coupling competition pathways of alkyl radicals produced by pyridyl ethers under visible light photocatalysis were proposed via related mechanism studies.Subsequently,we further focused on the homocoupling of benzyl radicals generated in the process.The strategy of N-methylation of pyridyl ethers before participating in visible light photocatalysis was still adopted.The visible-light-catalyzed deoxygenation and homocoupling reactions were accomplished only with benzyl pyridyl ethers and without other radical acceptors.These reactions provided a series of bibenzyl compounds widely found in bioactive molecular structures in 34-90%yields.In addition,this synthetic method can be further extended to the synthesis of imipramine which is an antidepressant drug.It is expected to be applied in the field of drug synthesis in the future.Finally,we successfully applied this novel visible-light-catalyzed deoxygenation and homocoupling process to allyl pyridyl ethers.This methodology provided a variety of 1,5-dienes in 41-96%GC-MS yields.Squalene,which has various applications,was successfully prepared by the method of this system.The visible-light-catalyzed deoxygenation and homocoupling system of allyl pyridyl ethers was demonstrated to be promising for the synthesis of natural products in the future.In summary,the visible-light-catalyzed deoxygenation/coupling reactions of pyridyl ethers enable inert ethers to participate in the photocatalytic coupling reactions,which expand the application scope of photocatalytic reactions.At the same time,this strategy provides a new methodology for the synthesis of many intermediates and bioactive compounds.