Superoxide anion radical (02.bul.-) mediated base-catalyzed autoxidation of .alpha.-keto enols

Abstract

Eight 4,4-disubstituted 2-hydroxycyclohexa-2,5-dien-1-ones were prepared by the base-catalyzed autoxidation (BCA) of the corresponding 4,4- or 5,5-disubstituted cyclohex-2-en-1-ones. Upon reaction with superoxide anion radical (O{sub 2}{sup {sm bullet}{minus}}, generated from KO{sub 2}/18-crown-6) in inert nonpolar aprotic media at room temperature, {alpha}-keto enols 3a-g undergo initial deprotonation of the enol hydrogen followed by BCA at C{sub 3} of the resulting enolate. Aqueous acid workshop of the reaction mixture yields lactols 4, while methyl iodide quenching generated 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 {delta}-valerolactones from the corresponding cyclohex-2-en-1-ones. 4,4-Diphenyl enol 3h, by contrast, resists BCA (whether mediated by O{sub 2}{sup {sm bullet}{minus}} or t-C{sub 4}H{sub 9}O{sup {minus}}) to the corresponding lactol yielding instead a variety of oxidative cleavage products 13-18. 2-Hydroxyspiro(4.5)dec-1-en-3-one (21) also underwent O{sub 2}{sup {sm bullet}{minus}}-mediated BCA, yielding diacids 22 and 26 as well as lactol 30. The synthetic applications of these results are also discussed.