Superoxide Anion Radical (o₂) •-) Mediated Base-catalyzed Autoxidation of Enones

Seventeen variously substituted cyclohex-2-en-l-ones were prepared and reacted with superoxide anion radical (O₂•-, generated from K0₂/18-crown-6) in inert nonpolar aprotic media at room temperature. The 4,4,6,6-tet-rasubstituted cyclohexenones (lb, lc, and ld) proved to be totally inert, while those cyclohexenones possessing available acidic a'- or 7-hydrogens underwent O₂•-mediated base-catalyzed autoxidation (BCA) generating various products depending on the nature and location of the substituents. Thus, 4,4- and 5,5-disubstituted substrates (2b, 2c, 2e, 2f and 3b, 3d, 3f-3i, respectively) gave 2-hydroxycyclohexa-2,5-dien-l-ones (7) as the major product (<80% yield) upon aqueous acid workup, while the corresponding 2-methoxy analogues 8 are obtained when the reaction is quenched with CH₃I. 2,3-Epoxycyclohexanones 13 and oxidative cleavage products 11 and 12 are formed in the case of the 6,6-disubstituted systems (4a-4c); these oxidation products are accompanied by dimers 14 when the substituent on 4 is CH₃or H. Epoxide 23 is the primary isolable product in the 3,4,4-trialkyl system (5d). As expected for BCA processes, similar results were observed when these reactions were mediated by KOH (at room temperature) or KOC(CH₃)₃(at -40 °C). In the case of 6,6-diphenylcyclohex-2-en-l-one (4c), however, tert-butoxide-mediated BCA at -40 °C yielded cyclopentene hydroxy acid 15 in addition to epoxide 13. The saturated analogue of 4c, 18, yielded primarily the corresponding saturated hydroxy acid 19, as well as several other oxidation products (20–22) depending on the reaction conditions. The mechanism of these transformations is rationalized in terms of base-induced reactions and rearrangements of the initially formed keto hydroperoxides.