Chiral bronsted acid catalyzed enantioselective alfa-amidoalkylation reactions in the synthesis of tetrahydroisoquinoline systems
- Autores: Eider Aranzamendi Uruburu
- Directores de la Tesis: María Nuria Sotomayor Anduiza (dir. tes.), Maria Esther Lete Exposito (dir. tes.)
- Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2014
- Idioma: inglés
- Tribunal Calificador de la Tesis: Claudio Palomo Nicolau (presid.), María Luisa Carrillo Fernández (secret.), María Magdalena Cid Fernández (voc.), Roberto Sanz Díez (voc.), Juan Antonio Rodríguez (voc.)
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- Resumen
The research work described in this thesis has focused on the study of enantioselective intra and intermolecular ¿-amidoalkylation reactions catalyzed by chiral Brønsted acids for the synthesis of tetrahydroisoquinoline systems. The intermolecular ¿-amidoalkylation reactions of hydroxylactams, generated by Parham cyclization of the corresponding imides, with nucleophiles, such as indoles and enamides that have an H bond donor group, catalyzed by sterically demanding BINOL-derived N-triflylphosphoramides and phosphoric acids, afforded moderate to good enantioselectivities. The reaction is proposed to take place via a bicyclic N-acyliminium /chiral conjugate base ion pair, in which the chiral Brønsted acid catalyst may act as a bifunctional catalyst, interacting also with the nucleophile.In a similar way, the enantioselective intramolecular ¿-amidoalkylation reaction requires phenolic activation on the benzene ring acting as internal ¿-nucleophile to achieve reasonable levels of enantioselection. In this case, different substituents can be introduced at C-1 position of the isoquinoline moiety by changing the organometallic reagent at the first step of the organometallic addition/intramolecular ¿-amidoalkylation sequence, giving rise to useful precursors for the construction of more complex alkaloids.
