Nickel Catalyzed Reductive Coupling For Formation Of C-S Bonds

Thioethers are widely found in pharmaceutical molecules and have been widely applied in the fields of materials and are used in many areas such as drug discovery.Therefore,development of efficient methods in construction of organic thioethers has been one of the most popular topics in organic chemistry.With the rapid development of sulfur chemistry,numbers of new sulfur-containing reagents have been well developed and utilized in the synthesis of thioethers.Traditional methods to prepare thioethers mainly lie on malodorous and expensive thiols/thiophenols as the sulfur sources,and transition metal catalytic reactions usually require high temperatures,strong bases,even use of expensive metals catalysts,newly designed special ligands.Compared to metals catalysts such as palladium and rhodium,the cheap and less toxic nickel displays its unique reactivities.This thesis describes the recent advance on the reductive coupling reactions of organic halides with structure-varied electrophilic sulfur reagents in presence of nickel catalysts.This thesis first describes the thiolation on development of transition metal-catalyzed cross-coupling to construct C-S bonds,and there are many critical issues remained to be solved in presence of metal-catalyzed reactions:(1)The thiol anions have a strong coordination effect on metal catalysts and tend to poison the transition metal,resulting in requirement of high catalyst loadings in the transformation;(2)Strong bases and higher reaction temperature limit the tolerance of functional groups;(3)Major of thiols and disulfides are not commercially available;(4)Poor substrate scope is achieved in photochemical and electrochemical reactions;(5)Preparation,storage and handling of organometallic reagents cause limited applications.In recent years,these problems have been alleviated or solved by applications of reductive coupling reactions(cross-coupling between two electrophilic reagents).We hope to develop efficient methods for construction of C-S bonds under mild reaction conditions to prepare a series of useful thioethers.Two parts involved in this research which are listed as follows.In the first part,we firstly pay our attention on the employment of different electrophilic sulfur reagents for reductive coupling.We plan to develop methods to form different C-S/Se bonds by Nickel-catalyzed aryl/alkyl/alkyne iodization with bench-stable S-phenylthiosulfonates under mild reaction conditions has been well developmed.The precise formation of C(sp~1)/C(sp~2)/C(sp~3)-S bonds was also achieved with this electrophilic sulfur-transfer-reagent.As a result,a series of structurally varied asymmetric thioethers are synthesized.The mild transformations are highlighted with excellent functional group tolerance,low catalyst loading and excellent chemoselectivity.In the second part,we have developed an efficient,’thiophenol/thiol-free’and sustainable method to prepare a wide range of N-thiophthalimides from readily available aryl and alkyl zinc reagents.Moreover,thiolation under base-free conditions employs only 0.5 mol%nickel catalyst loading have also been developed,with late-stage modification of biologically complex drug molecules,subsequent synthesis of important compounds and recycling of the original starting materials.