Eosin-Y-Catalyzed Visible-Light-Driven Ferrier Rearrangement of Glycal C3-Imidates

Ferrier rearrangements of glycals hold a special niche in glycochemistry for the formation of the fascinating 2,3-unsaturated glycosides that provide facile access to rare sugars, complex glycosides, and valuable synthetic intermediates for chiral natural products. The classical transformation involving the removal of the C3-leaving group from glycals is accomplished by Lewis and protic acids as reagents or catalysts, where the use of metal salts, strong acidic reagents, and temperatures above ambient conditions makes the strategy less sustainable. We herein report the activation of C3-imidates on glycals by low catalyst loading of eosin-Y as an organic photoacid and cocatalyst Ph₂S₂ in the presence of blue light for O-Ferrier rearrangements. The visible light-driven strategy circumvents the formation of byproducts like C1-amides and 2-deoxyglycosides with chemoselective generation of Ferrier adducts from both gluco- and galacto-configured glycals. The mild reaction conditions were well-tolerated by acid-sensitive acetal protecting groups on the glycals. Further, the substrate scope was studied with a wide range of nonsugar alcohols, monosaccharide-based alcohols, and phenols to obtain the desired products in good to excellent yields. Control experiments reveal the significance of imidate as the leaving group for the photoacid-catalyzed transformation and the requirement of blue light for the observed reaction outcome.