Catalytic Radical Reactions of Unsaturated Sugars

Abstract

The functionalization of unsaturated carbohydrates is a powerful approach for the synthesis of a variety of glycoside derivatives, sugar mimics, and enantiomerically pure molecules. This Review will discuss recently developed catalytic radical methods for the functionalization of glycals, exo-glycals, and exo-enes, highlighting the opportunities they offer for new reaction design. While providing new routes for the synthesis of complex carbohydrates, catalytic radical transformations of unsaturated sugars overcome the limitations that typically affect classical protocols, such as the use of stoichiometric oxidants/reductants and hazardous and toxic reagents. Currently unaddressed challenges will also be discussed, suggesting new directions for future work and fostering new methodological developments and applications in the field.

Advances on the Synthesis of C-Aryl-glycosides Since 2019

“…The carbohydrate community has also recognized the potential of these catalytic methods, leading to their application in carbohydrate synthesis. 27 The generation of alkyl radicals through carbon-oxygen bond cleavage has made significant progress, with esters of levulinic acid, oxalic acid, and phosphonic acid being able to activate hydroxy groups to produce alkyl radicals. However, these methods have not been applied to activate hydroxy groups at non-anomeric positions of sugars, possibly due to the inherent instability of such compounds.…”

“…The carbohydrate community has also recognized the potential of these catalytic methods, leading to their application in carbohydrate synthesis. 27…”

From Sweet Molecular Giants to Square Sugars and Vice Versa

“…The innate preference of pseudoanomeric radicals for an axial conformation was expected to ensure a high degree of α-selectivity. 130 131 In addition, the broad substrate scope of iron-mediated Michael–Giese hydroalkylation of olefins reported by Baran 132 theoretically enabled the introduction of structural diversity at the pseudoanomeric quaternary center.…”

Visible-Light-Promoted Desulfurization to Synthesize Deoxyglycosides

“…The synthesis of deoxyglycosides, especially 2-deoxyglycosides, has been identified as one of the most important areas in carbohydrate chemistry since deoxysugar fragments are frequently present in many biologically active natural products. − Deoxysugar synthesis methods typically involve the modification of hydroxyl groups and subsequent reduction. The reported methods involved dehalogenation, − desulfurization, − reduction of glycals, − and reduction of glycosides with thiocarbonyl groups − and sulfonates, − where Raney nickel or Pd-catalyzed hydrogenation is the most commonly used means. A well-designed strategy for deoxysugar synthesis should be an ingenious combination of a concise hydroxyl modification process with a suitable hydrogenation method, especially for the synthesis of 2-deoxyglycosides.…”