Synthesis of novel isoxazoline and isoxazolidine derivatives: carboxylic acids and delta bicyclic lactones via the nucleophilic addition of bis(trimethylsilyl)ketene acetals to isoxazoles

Abstract

Bis(trimethylsilyl)ketene acetals readily react with activated N-triflyl isoxazoles to selectively afford novel isoxazoline or isoxazolidine derivatives. The regioselectivity of the reaction strongly depends on the substrate substituents. When the isoxazole is substituted at the 5-position by a methyl or phenyl group, the lactonization product, i.e., the isoxazolidine derivative, is formed as a result of double nucleophilic addition of the ketene acetal. When the isoxazole is not substituted, the main product is the corresponding carboxylic acid, i.e., the isoxazoline derivative.