Electrochemical Radical Cyclization To Construction Of Five/Six-Membered Nitrogen-Containing Heterocycles

Heterocyclic compounds are one of the important backbones of natural products and drugs,constituting a very common fragment of many active pharmaceutical ingredients as well as excipients.It is estimated that more than 85% of biologically active chemicals contain heterocycles.Therefore,many methods have been developed for the synthesis of nitrogen-containing heterocycles,but most of them rely on a variety of metal catalysts and external oxidants,which have poor atomic utilization and generate chemical waste,even causing environmental pollution.Electrochemical organic synthesis has gradually become a popular means of organic synthesis in recent years,because it does not require the addition of additional oxidizing or reducing agents,and the activation of the raw material molecules themselves through the redox process on the electrode,so as to carry out the next step of the reaction,which is favored by many researchers.Moreover,this approach is more in line with the need for atomically economical and green chemistry.Second,electrochemical synthesis allows manipulation of the potential or current of the reaction electrode,so that researchers can activate relatively poorly activated substrates or sites without any prefunctionalization of the substrate,thus improving the step and economy of the synthetic route.At the same time,the potential control of these reactions allows one to further perform the reactions under mild conditions,thus providing excellent functional group tolerance.All these make electrochemical organic synthesis a valuable and sustainable approach in organic synthesis.Therefore,this paper focuses on the study of electrochemical radical cyclization for the construction of five/six-membered carbon heterocyclic ring reactions.The study mainly includes the following parts:(1)In this thesis,a series of indazoles were synthesized by using easily prepared aryl hydrazones as raw materials,and the mechanism of nitrogen-centered radical formation was preliminarily investigated by obtaining reactive nitrogen-centered radicals,followed by intramolecular cyclization and construction of C-N bonds.The expansion of the substrate reveals the compatibility of the reaction.Inexpensive electrodes,mild reaction conditions,and an expanded reaction with satisfactory yields opened up the possibility of practical applications of this reaction.(2)A series of heterocyclic compounds containing sulfur cyanide was constructed by choosing ammonium thiocyanate,which is easy to obtain,use and low toxic,as the sulfur source and enamide as the raw material,and by generating radicals with the help of electrochemical anodic oxidation and choosing a radical tandem cyclization strategy.And the reaction has a wide range of functional group compatibility with good to excellent yields.Notably,the resulting thiocyano is one of the building blocks of functional group transformation,which can be used for the synthesis of functionalized benzoxazine derivatives.