Biphasic Electrosynthesis of 2-Isoxazol(in)e-3-carboxylates: Reaction Optimization from Milligram to Hectogram Scale

An electrochemical synthesis of isoxazol(in)e-3-carboxylates in a biphasic system allowing the direct access to technically relevant motifs in good yields has been established. The versatility of this protocol was demonstrated by >30 highly functionalized and diverse examples. Furthermore, a derivative of isoxadifen-ethyl was synthesized in a more sustainable approach, avoiding hazardous reagents and the generation of large amounts of waste. A nitrile oxide as the key intermediate is formed without addition of strong bases or oxidizers and directly undergoes the desired cycloaddition. The technical relevance of the established method was underlined by hectogram-scale synthesis while purifying the crude product by simple silica filtration. By simple distillation, nonconverted styrene was largely recovered, demonstrating the sustainability of this method.