Mechanism of SeO2 promoted oxidative rearrangement of 2-substituted oxazolines to dihydrooxazinones: Isotopic labeling and kinetic studies

Article abstract of DOI:10.1016/0040-4020(96)00902-7

The mechanism of the recently reported SeO₂ promoted oxidative rearrangement of 2-alkyl oxazolines was investigated. ¹³C labeling studies with 1a-2-¹³C showed that rearrangement proceeds by fission and migration of the C=N bond, not the C-C bond as first proposed. Oxidation-rearrangement of 1 proceeds by rapid SeO₂ promoted oxidation to 2-acyloxazoline 3 followed by slower rearrangement of 3 to oxazinone 2. The second order rate constant for the oxidation step for 2,4-diphenyloxazoline 1b in 1,4-dioxane at 40°C was k₁ = 2.85 ± 0.62 x 10^-2 M^-1·s^-1. The second and rate limiting rearrangement step (3b → 2b) had a first order rate constant of k₂ = 1.15 ± 0.09 x 10^-3 s^-1 while the relatively low apparent energy of activation E(A) of 4.2 ± 1.6 kcal·mol^-1 in the presence of 2.0 equiv of SeO₂ suggests heterogeneous catalysis. The reaction is catalyzed by Lewis acids, including SeO₂ or small amounts of H₂O. A plausible mechanism is proposed involving Lewis acid activation and nucleophilic catalysis with H₂O.