Reaction of superoxide with ascorbic acid derivatives: Insight into the superoxide-mediated oxidation of dehydroascorbic acid

Article abstract of DOI:10.1021/jo00114a031

In order to gain greater insight into the mechanism of superoxide-mediated oxidation of ascorbic acid (1) in aprotic media, we reacted O₂^.- (generated from KO₂/18-crown-6 in toluene) with vitamin C derivatives 13a and 14a and the corresponding mono- and dimethoxy analogs 13b and 13c, respectively. Dihydroxyfuranones 13a and 14a underwent oxidative cleavage with O₂^.- yielding, upon methyl iodide workup, the corresponding keto ester (15 or 17, respectively) and threonic acid analog (16 or 18, respectively). On the other hand, mono- and dimethoxy analogs 13b and 13c each react with superoxide to give a single isolable product, oxyester 16 and alkylidenefuranone 20, respectively. Finally, 13a reacts with tert-butoxide, again yielding 16 as the major product. The data are best resolved by suggesting that ascorbic acid analogs 13a and 14a (and presumably ascorbic acid as well) are oxidized by O₂^.- to the corresponding triketone 21 which reacts in turn by attack at the highly electrophilic central carbonyl C-2. Cyclization of the resulting 2-peroxy 1,3-diketone 22 into the C-1 carbonyl, followed by oxidative cleavage, saponification, and methylation, yields the observed products. By contrast, O₂^.- oxidation of 13b and tert-butoxide oxidation of 13a yield 3-peroxy-1,2-diketone 29 which cyclizes into the C-1 carbonyl ultimately yielding 16. Finally, 13c, which lacks enolic hydrogens, undergoes abstraction of the γ-hydrogen followed by the elimination of acetone, yielding 20. Similarly, 5,6-dihydropyrone 33 undergoes superoxide-mediated elimination yielding dienone 34. The data presented herein are consistent with the mechanism suggested by Sawyer et al. (J. Am. Chem. Soc. 1982, 104, 6273-6278) for the superoxide-mediated oxidation of dehydroascorbic acid (2) - with the modification that the position of initial O₂^.- attack is at the C-2 (rather than the C-3) carbonyl.