Activación de aldehídos a,b-insaturados mediante aminocatálisis en procesos enantioselectivos. Cicloadiciones (3+2) y reacciones en cascada Michael/Henry

  1. Fernández Hernández, Naiara
Supervised by:
  1. María Luisa Carrillo Fernández Director
  2. José Luis Vicario Hernando Director

Defence university: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 26 October 2012

Committee:
  1. Miguel Yus Astiz Chair
  2. Olga García Mancheño Secretary
  3. Gonzalo Blay Llinares Committee member
  4. Maria Esther Lete Exposito Committee member
  5. Anna Roglans Ribas Committee member
Department:
  1. Química Orgánica e Inorgánica

Type: Thesis

Teseo: 115445 DIALNET lock_openADDI editor

Abstract

During the research that it is summarized in the present memory, the activation of enals via iminium ion catalysis in different transformations has been studied. Firstly, a 1,3-dipolar cycloaddition between stable azomethine ylides and a,b-unsaturated aldehydes catalyzed by a chiral imidazolidinone derivative has been optimized. Employing this methodology we have synthesized a large range of densely substituted pyrroloisoquinolines and pyrrolophthalazines with good yields and high values of diastereo- and enantioselectivity. Moreover, a mechanistic study has been carried out based on DFT calculations and experimental data which have allowed us to propose that the (3+2) cycloaddition reaction follows a sequential Michael addition/Mannich cyclization pathway. The formation of the iminium ion as a result of the condensation between the a,b-unsaturated aldehyde and the catalyst plays an essential role, regarding both reactivity and stereoselectivity. On the other hand we have developed a methodology to carry out a cascade Michael/Henry reaction followed by a sequential dehydration. Starting from simple substrates (2-nitromethylacrilates and a,b-unsaturated aldehydes) and employing a prolinol-derivative catalyst a series of quiral nitrocyclohexadienes have been synthesized.