Free‐Radical Epimerization of d‐ into l‐C‐(Glycosyl)methanol Compounds Using 1,5‐Hydrogen Atom Transfer Reaction

Abstract

AbstractA simple epimerization of C‐(α‐d‐Glyp)methanol into C‐(β‐l‐Glyp)methanol compounds is described. The radical sequence involved homolytic cleavage of the C5−H bond by 1,5‐hydrogen atom transfer promoted by the 1’‐O‐yl radical and subsequent hydride addition with inversion of configuration. This methodology allows the preparation of rare C‐(β‐l‐Idop)‐, C‐(β‐l‐Altp)‐, C‐(β‐l‐Gulp)‐, C‐(β‐l‐Allp)methanol glycosides starting from carbohydrates of the d‐series. It can also be applied to transform l‐ into d‐configured C‐glycosyl compounds, as illustrated by the formation of C‐(β‐d‐6dGulp)‐ and C‐(β‐d‐6dAltp)methanol from readily accessible l‐rhamno and l‐fuco analogs, respectively. In further development of this procedure compounds with C‐(β‐l‐Araf)‐ and C‐(β‐l‐5dRibf)methanol structures have also been synthesized. The alkoxyl radicals were generated by reaction of the corresponding N‐alkoxyphthalimides with nBu3SnH(D) and in comparative terms, by visible light‐photocatalysis using the Hantzsch ester/fac‐Ir(ppy)3 procedure. The influence of the sugar ring conformation and the electronegativity of the substituents on the stereochemical outcome will be addressed.