A Solvolytic C−C Cleavage Reaction of 6-Acetoxycyclohexa-2,4-dienones: Mechanistic Implications for the Intradiol Catechol Dioxygenases

Abstract

6-Acetoxycyclohexa-2,4-dienones are found to undergo a rapid reaction in methanol/water under mildly basic conditions to give an acyclic ketoester as the major product for 6-phenyl and 6-methyl substrates. Reaction monitoring by UV spectroscopy indicates the formation of an unsaturated ketone reaction intermediate (λmax 275 nm, R = Ph) and the transient appearance of a highly conjugated species. Reaction of the 6-phenyl substrate (4.95 × 10-6 s-1) is 2-fold faster than the 6-methyl substrate (2.47 × 10-6 s-1). The reaction rate is first order with respect to substrate concentration, and the final step in the reaction is pH-dependent. No cleavage was observed for a substrate lacking an acetyl substituent. A reaction mechanism for C−C cleavage is proposed involving a benzene oxide−oxepin interconversion. The possible relevance to the catalytic mechanism of the intradiol catechol dioxygenases is discussed.