DOI: https://doi.org/10.24820/ark.5550190.p011.500 Page 197 © AUTHOR(S) A Platinum Open Access Journal for Organic Chemistry Paper Free to Authors and Readers DOAJ Seal Arkivoc 2021, part iii, 197-209 Synthesis of novel isoxazoline and isoxazolidine derivatives: carboxylic acids and delta bicyclic lactones via the nucleophilic addition of bis(trimethylsilyl)ketene acetals to isoxazoles Saulo C. Rosales-Amezcua, a Ricardo Ballinas-Indili, a Morelia E. López-Reyes, b Héctor A. Rosas-Castañeda, a R. Alfredo Toscano, a Cecilio Álvarez-Toledano * a a Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, Ciudad Universitaria, Cd. de México, 04510, México b Departamento de Química, Universidad de Guadalajara, Blvd. Marcelino García Barragán 1421, Guadalajara, 44430, México Email: cecilio@unam.mx This paper is dedicated to the successful career of Professor Lanny Liebeskind Received 02-25-21 Accepted 04-19-2021 Published on line 04-30-2021 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. Keywords: Ketene acetals, isooxazoline, isoxazolidine, lactone, N-triflyl activation