Superoxide Anion Radical (O₂)•^-Mediated Base-catalyzed Autoxidation of α-keto Enols

Eight 4,4-disubstituted 2-hydroxycyclohexa-2,5-dien-l-ones were prepared by the base-catalyzed autoxidation (BCA) of the corresponding 4,4- or 5,5-disubstituted cyclohex-2-en-l-ones. Upon reaction with superoxide anion radical (0₂^-, generated from K0₂/18-crown-6) in inert nonpolar aprotic media at room temperature, a-keto enols 3a-g undergo initial deprotonation of the enol hydrogen followed by BCA at C₃of the resulting enolate. Aqueous acid workup of the reaction mixture yields lactols 4, while methyl iodide quenching generates methoxy lactones 5. Lactols 4 can be readily converted to their acetoxy analogues 8, opened to aldehydo methyl esters 6, or reduced to the related lactones 7. The latter suggests a convenient one-pot synthesis of 2,3-unsaturated 6-valerolactones from the corresponding cyclohex-2-en-l-ones. 4,4-Diphenyl enol 3h, by contrast, resists BCA (whether mediated by O₂^-or t-C₄H₉0^-) to the corresponding lactol yielding instead a variety of oxidative cleavage products 13–18. 2-Hydroxyspiro[4.5]dec-l-en-3-one (21) also underwent O₂ ^--mediated BCA, yielding diacids 22 and 26 as well as lactol 30. The synthetic applications of these results are also discussed.