DIASTEREOSELECTIVE SYNTHESIS OF 4-HYDROPEROXY-3,5-CYCLOHEXADIENONES IN THE PHOTOOXYGENATION OF HYDROXYETHYL-SUBSTITUTED PHENOLS

Three of the four possible isomeric para-substituted hydroxyethyl-meth ylphenols were prepared from readily available starting materials and submitted to photooxygenation. In the case of 3-hydroxy-alpha,6-dimeth ylbenzenemethanol (1a) and 2-hydroxy-alpha,5-dimethylbenzenemethanol ( 1b) the corresponding 4-hydroperoxy-3, 5-cyclohexadienones were obtain ed as oxy-functionalized products (greater than or equal to 90%, d.r. 85:15 and 75:15). The stereochemistry of the products was assigned aft er reduction to the corresponding p-quinols. The ready cleavage of the initial oxygenated product, which can be observed at low temperature as a single diastereomer, prevented rigorous assignment of the pi-faci al selectivity of the singlet oxygen attack for the derivative 4-hydro xy-alpha,2-dimethylbenzenemethanol (1c). The present stereochemical re sults indicate that the hydroxyl group directing effect, that is, coor dination of the incoming singlet oxygen dienophile with the hydroxyl g roup, is also operating in the photooxygenation of the chiral phenols 1a-c. However, in the case of the derivative 1b, hydrogen bonding in t he starting material leads to an opposite stereochemical outcome. This conclusion is further substantiated by solvent effects and the fact t hat the methyl ether 1d of alcohol 1c displays a significant lower dia stereoselectivity.