Anion-Bridged Dual Hydrogen Bond Enabled Concerted Addition of Phenol to Glycal

A noncovalent organocatalytic concerted addition of phenol to glycal is developed for the stereoselective and regioselective construction of biologically important phenolic 2-deoxyglycosides, featuring wide substrate tolerance. The method relies on an anion-bridged dual hydrogen bond interaction which is experimentally proved by Nuclear Magnetic Resonance (NMR), Ultraviolet and visible (UV-vis), and fluorescence analysis. Experimental evidence including kinetic analysis, Kinetic Isotope Effect (KIE) studies, linear free energy relationship, Hammett plot, and density functional theory (DFT) calculations is provided for a concerted mechanism where a high-energy oxocarbenium ion is not formed. In addition, the potential utility of this method is further demonstrated by the synthesis of biologically active glycosylated flavones. The benchmarking studies demonstrate significant advances in this newly developed method compared to previous approaches. A concerted addition of phenol to glycal promoted by anion-bridged dual hydrogen bond interaction is disclosed, featuring excellent stereoselectivity and broad substrate tolerance. The unprecedented concerted addition pathway is confirmed by kinetic analysis, KIE studies, Hammett plot and DFT calculation. The synthesis of biologically active glycosylated flavones and benchmarking studies demonstrate the significant advance of this method.image