Silicon Chiral Phosphine Ligand Controlled Asymmetric Copper-Catalyzed Huisgen Cycloaddition Reaction

Since the chemistry of Huisgen alkyne-azide cycloaddition,also often referred to concept of“Click”addition was first introduced by the groups of Sharpless and Meldal,copper-catalyzed alkyne-azide cycloaddition reaction?CuAAC?has been intensively recognized as a powerful carbon-nitrogen bond-forming reaction for the facile synthesis of a range of structurally diversity triazoles that are prevalent in many research areas of chemistry,materials,biology,pharmaceutical and environmental science.In particular,the asymmetric version of CuAAC has also been reported in the past decade.However,there are few examples reported on the asymmetric Huisgen cycloaddition.Thus the previous and limited reports suggested that the enantioselective CuAAC with desymmetrization,or referred to asymmetric click chemistry?ACC?had powerful potential for the enantioselective construction of structurally diversity and optically pure triazoles.Firstly,we have successfully applied chiral phosphines with multistereogenic centres of axial and sp3-central from a signal chiral source BINOL,simplified as Tao-Phos,in the enantioselective catalytic asymmetric Huisgen[3+2]cycloaddition of azides and alkynes.It was found that the catalytic Huisgen cycloaddition reaction of succinimide-derived bisalkynes with azides resulted in the useful succinimide-derived triazoles bearing quaternary carbon-stereogenic center with good to excellent yields as well as good chemoselectivity and moderate to high enantioselectivities?up to 97%ee?,in which the CuF₂/Tao-Phos complex was proved to be an effective bimetallic catalyst in the presence of triethyl amine.The mechanistic studies based on the effect of reaction parameters on stereoselectivity as well as ESI-MS analysis suggested that our ligand?Tao-Phos?and related binuclear copper centers play crucial role in this asymmetric click chemistry because of the strong catalyst-substrate interaction with the aid of possibly in-situ formed binuclear or multinuclear copper-based transition state.This work not only provides a new example accounting for the Cu?II?-mediated asymmetric AAC reactions involving chelating base and azides,but also suggests the significance of binuclear copper species in catalytic asymmetric click reactions where two copper centers-involved enantioselective inductions.In addition,we have also investigated the role of multifunctional and multiple stereogenic P-ligand,Tao-Phos and its analogues,in the copper nanoparticles–catalyzed azide alkyne cycloaddition of pyrazolone–derived bisalkynes.In this work,we have further determined that the privileged role of Tao-Phos in controlling copper-catalyzed desymmetrization of other bisalkynes,which gave the corresponding triazoles in good enantioselectivity and yields.