Chiral bronsted acid catalyzed enantioselective alfa-amidoalkylation reactions in the synthesis of tetrahydroisoquinoline systems

Supervised by:
  1. María Nuria Sotomayor Anduiza Director
  2. Maria Esther Lete Exposito Director

Defence university: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 19 December 2014

  1. Claudio Palomo Nicolau Chair
  2. María Luisa Carrillo Fernández Secretary
  3. Juan Antonio Rodríguez Committee member
  4. María Magdalena Cid Fernández Committee member
  5. Roberto Sanz Díez Committee member
  1. Química Orgánica e Inorgánica

Type: Thesis

Teseo: 118103 DIALNET


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.