Acid-Base Catalyzed Formation of 2-Isoxazolines

Significance

Reported is the anilinium salt catalyzed synthesis of 2-substituted isoxazolines from reaction of α,β-unsaturated aldehydes, and oximes. Diethylketone oxime was selected as the reaction partner possessing the best combination of reactivity, stability, and utility; however, the oximes of acetone and acetaldehyde may be used but the desired isoxazoline requires purification by distillation. A mechanism, involving initial iminium-catalyzed conjugate addition of the oxime to the aldehyde, followed by hydrolysis-driven cycli­zation is proposed, but other mechanisms cannot be ruled out. The reaction may also be promoted by acid alone. However, since there is a significant induction period, the formation of a new catalytic species is implicated and perhaps is responsible for the failure of formation of enantioenriched products.