C-H Sulfuration Of Imidazopyridines Using Elemental Sulfur

Sulfur-containing compounds are an important class of organic compounds,which have been widely used as pharmaceuticals,agrochemicals and materials.Elemental sulfur is an ideal sulfur reagent that is nontoxic,odorless,stable,easy to handle and store.Imidazopyridines are an important kinds of drug skeletons.The introduction of sulfur-containing bioactive motifs into imidazopyridines through C-H bond sulfuration using elemental sulfur is significant for drug design and development.This paper focuses on the study of C-H sulfuration of imidazopyridine using elemental sulfur as the sulfurating reagent for the diversity construction of imidazopyridine derivatives.This thesis consists of four chapters.In the first chapter,the progress on the application and development of elemental sulfur in organic synthesis in the past decade is reviewed.The C–H bond thionation,trifluoromethyl sulfuration,alkyl sulfuration,sulfur-containing heterocyclic synthesis,synthesis of thioamides,P–S bonds formation,and elemental sulfur as an oxidant are summarized and commented,respectively.The second chapter describes a metal-free oxidative radical dual C–H bond sulfuration using elemental sulfur that is a green,non-toxic,stable reagent.The three-component sulfuration of imidazopyridine,elemental sulfur and ether or alkane proceeded well in the presence of DTBP.Under the reaction conditions,the C（sp³）–H bonds of cyclic ethers,chain ethers,cycloalkanes,chain alkane,and benzyl could be activated for sulfuration.Several epoxides also underwent the sulfuration to afford the correspondingβ-hydroxy thioethers.In the third chapter,a metal-free alkyl sulfuration of imidazopyridine with diverse halogenated hydrocarbons using elemental sulfur has been developed.It was found that TMEDA could promote the C（sp²）-H sulfuration of imidazopyridiens with halogenated hydrocarbons and elemental sulfur.A variety of functional groups,such as halogen atoms,polyfluoro alkyl,internal olefins,terminal olefins,terminal alkynes,cyano,acetals,and ester groups,are tolerated well under the reaction conditions.These functional groups are important bioactive motifs or building blocks for organic synthesis and drug development.The fourth chapter focuses on the development of oxidative radical dual C-H bond functionalization strategy for thiocarbamation of imidazopyridines with elemental sulfur and formamide.In the presence of the catalytic Cu（OTf）₂,NBS and DTBP,the three-component sulfuration proceeded smoothly to afford the corresponding products in moderate to good yields.