Isotope Effects and the Mechanism of Allylic Hydroxylation of Alkenes with Selenium Dioxide

The mechanism of the allylic oxidation of 2-methyl-2-butene with selenium dioxide was explored by a combination of experimental and theoretical studies. A comparison of the experimental 13C and 2H kinetic isotope effects with predicted values shows that the observed isotope effects are consistent with an initial concerted ene step mediated by SeO2. However, this comparison also does not rule out the involvement of a selenous ester in the ene reaction or a stepwise reaction involving reversible electrophilic addition of HSeO2 + followed by rate-limiting proton abstraction. Becke3LYP calculations strongly favor SeO2 over a selenous ester as the active oxidant, with the predicted barrier for reaction of 2-methyl-2-butene with SeO2 being 21−24 kcal/mol lower than that for reaction with H2SeO3. The possibility of a selenous ester being the active oxidant is also disfavored by the observation of oxidations in non-hydroxylic solvents. The involvement of HSeO2 + does not appear consistent with a lack of dependence of the reaction on the basicity of the reaction mixture. A concerted ene reaction with SeO2 as the active oxidant appears to be the major mechanistic pathway operative in these reactions.