Nickel-Catalyzed Reductive Carbamoylalkylation Of Alkenes And Reductive Alkylation Of α-Trifluoromethyl Alkenes

In recent years,nickel-catalyzed reductive functionalization of alkenes received extensive attention owing to its wide substrate scope and excellent functional group tolerance,and has emerged as a powerful tool for the construction of complex molecules.In the first chapter of this dissertation,the background of this reaserch field is described.Nickel-catalyzed asymmetric functionalization of tethered alkenes is a powerful method for construction of chiral cyclic compounds.However,previous reports are limited to nickel-catalyzed asymmetric carbo-arylation of tethered alkenes.Herein,we report the first reductive enantioselective alkyl-carbamoylation of tethered alkenes.This strategy is not only able to construct chiral quaternary carbon center efficiently,but also demonstrates wide substrate scope and good functional-group tolerance as well.By employing carbamoyl chloride-tethered alkenes and alkyl halides as precursors,this method provides complex chiral oxindoles in high efficiency via reductive enantioselective alkyl-carbamoylation of alkenes.Systematic screening of chiral ligands suggested that the newly synthesized PyrOx possessed the best performance.In the last part of this chapter,we proposed a possible pathway for the reaction based on previous reports and a number of control experiments.On the other side,as the gem-difluoroalkene moiety is known to serve as a carbonyl bioisostere with less susceptibility to in vivo metabolism leading to improved pharmaceutical performance,it has attracted enormous interest from organic chemists.In chapter three,a highly efficient synthetic method to synthesize gem-difluoroalkenes via nickel-catalyzed reductive alkylaltion/defluorinative cross-coupling reaction of a-trifluoromethyl alkenes with alkyl halides was developed.Compared with the conventional strategies of construction of the gem-difluoroethylene motif,this reaction is easy to handle,employs readily available starting materials,demonstrates excellent functional group tolerance and proceeds under mild reaction conditions.Moreover,this method proves to be suitable for late-stage functionalization of multifunctional complex molecules.Finally,we revealed the reaction pathway by performing a series of control experiments,and proposed a reaction mechanism.We achieved two types of functionalization of alkenes via reductive nickel-catalysis,providing new strategies for the synthesis of chiral oxindoles and gem-difluoroalkenes.Moreover,we preliminarily revealed the possible reaction mechanisms for these synthetic protocols,building up solid foundation for further developments in the future.However,drawbacks of these reactions lie in several aspects,for instance,the relatively low efficiency in the synthesis of gem-difluoroalkenes using primary alkyl iodides and the failure to reach excellent enantiomeric excess in the construction of chiral oxindoles.Great efforts should be devoted to overcome these disadvantages.