The Mechanism of Oxidation of Allylic Alcohols to α,β-Unsaturated Ketones by Cytochrome P450

The oxidation of cyclohex-2-en-1-ol, a simple model substrate for allylic alcohols, is catalyzed by several P450 isoenzymes and leads exclusively to cyclohex-2-en-1-one. No double bond epoxidation or C(4) hydroxylation have been observed. The large primary kinetic isotope effect measured using [²H]-1-cyclohex-2-en-1-ol is consistent with an at least partially rate limiting breaking of the C(1)−H bond. The mass spectrometric analysis of cyclohex-2-en-1-one obtained from [¹⁸O]cyclohex-2-en-1-ol has established that a gem-diol intermediate is involved, even if a dual hydrogen abstraction pathway may contribute to the reaction.