Substrate-Controlled Diastereoselective Synthesis of Sugar-Based Chlorinated Perhydrofuro[2,3-b]pyrans via Copper(I)-Catalyzed Radical Cyclization

The work describes the first copper(I) chloride/2,2'-bipyridine-catalyzed atom transfer radical cyclization (ATRC) of unsaturated carbohydratederived chloroacetals to generate chlorinated perhydrofuro[ 2,3-b] pyrans via an effective diastereoselective route. Various glycals (glucal, galactal and lactal) underwent the Ferrier rearrangement with 2,2,2-trichloroethanols to give acetal precursors stereoselectively, R-selective with galactal in contrast to S-selective with glucal. The radical cyclization of the Ferrier products occurred smoothly to afford cis-fused bicyclic products with the transfer of the chlorine atom at the non-anomeric carbon in the cyclized radical intermediate predominantly from the equato-rial direction. The carbohydrate templates controlled the stereochemistry of both Ferrier rearrangement and ATRC steps. The stereostructures of the products were also supported by single crystal X-ray diffraction crystallography. The products possess biologically important structural segments such as a glycosidic linkage, a fused bicyclic acetal unit and a chlorosugar unit which are potential sources for biological studies and further synthetic elaborations.