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

Abstract

AbstractThe work describes the first copper(I) chloride/2,2′‐bipyridine‐catalyzed atom transfer radical cyclization (ATRC) of unsaturated carbohydrate‐derived 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 equatorial 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.magnified image