Exploring prins and tandem cyclization approach for the assembly of tetrahydropyran frameworks

• Autores: Paula González Andrés
• Directores de la Tesis: María Asunción Barbero Pérez (dir. tes.)
• Lectura: En la Universidad de Valladolid ( España ) en 2025
• Idioma: inglés
• Tribunal Calificador de la Tesis: Jose M. Sansano Gil (presid.), Luis Ángel López García (secret.), Teresa Margarida Vasconcelos Dias Pinho Melo (voc.)
• Programa de doctorado: Programa de Doctorado en Química por la Universidad de Valladolid
• Menciones:
  • Internacional
• Calificación: Sobresaliente Cum Laude
• Materias:
  • Química
    • Química orgánica
• Enlaces
  • Tesis en acceso abierto en: UVADOC
• Resumen

  • Heterocycles are common scaffolds present in a wide range of natural and bioactive compounds. Consequently, many research groups have been devoted to develope new and efficient strategies for their synthesis. In this context, Prins cyclization and its variant, silyl-Prins cyclization, have emerged as potent techniques for the synthesis of different ring-size heterocycles, especially 6-membered oxacycles, or tetrahydropyrans. Considerig the presence of this motif in numerous natural products, we have focused on stablishing new strategies for their synthesis.

    Initially, we investigated the key aspects that influence the silyl-Prins cyclization of gem-vinylsilyl alcohols. To this end, we performed the reaction using different Lewis acids and varying the substituents on the silyl group of the starting alcohol, leading to the formation of a range of 6-membered oxacycles. Moreover, computational analyses were performed in order to gain insight into the reaction mechanism.

    Next, we focused on the Prins cyclization of terminal cyclopropylsilyl and cyclopropyl alcohols to access polysubstituted tetrahydropyrans. These oxacycles featured a C4-halogenated quaternary stereocenter, formed in a highly stereoselective manner. The cyclization proceeded in high yield for a wide range of aldehydes, alcohols and halogenating agents.

    Finally, we decided to explore the tandem Sakurai-Prins reaction of allylsilyl alcohols to obtain 6-membered oxacycles. The reaction afforded cis-2,4,6-tetrahydropyrans in a very stereoselective manner for a wide range of alkylic aldehydes.