Regulation of Alkoxyl Radical Reactivity via Sugar Ring Induction: Monofluoromethoxylation for Carbohydrate

Fluoroalkyl ethers are an important class of functional groups that have been widely used in the fields of pesticides and pharmaceuticals due to their unique chemical properties. However, incorporating this group into molecules poses significant challenges. This work presents a novel approach to address this issue. By utilizing sugar groups to modulate the reactivity of alkoxyl radicals, shifting from 1,5-hydrogen transfer to C-C bond cleavage followed by direct fluorination, this method avoids the use of difficult-to-synthesize and unstable monofluoromethoxylation reagents, enabling the monofluoromethoxylation of sugar molecules. This method demonstrates good substrate applicability for reactions involving both pyranoses and furanoses. In terms of the mechanism, control experiments confirm that the reaction is initiated by alkoxy radicals. Furthermore, although DFT calculations demonstrate that 1,5-hydrogen migration is more facile than C-C bond cleavage, the experimental results reveal that only C-C bond cleavage occurs in the reaction, leading to the formation of the target product.