Novel enantioselective aminocatalytic processes by means of vinylogous reactivity and photoredox catalysis
- Autores: David Bastida Borrell
- Directores de la Tesis: Paolo Melchiorre (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2015
- Idioma: español
- Tribunal Calificador de la Tesis: Marco Bandini (presid.), Ruben Martin Romo (secret.)
- Programa de doctorado: Programa de Doctorado en Ciencia y Tecnología Química por la Universidad Rovira i Virgili
- Materias:
- Texto completo no disponible (Saber más ...)
- Resumen
During the last 15 years, the field of organocatalysis, based on the condensation of aminocatalysts with carbonyl compounds, has been growing at an impressive pace. The cheap and relatively easy-to-perform experimental procedures, together with the high reliability of the modern organocatalytic tools to ensure high reaction efficiency, attracted a great number of research groups.
Developing new catalytic reactions is a must to address the synthetic challenges faced by organic chemists. In the realm of enantioselective organocatalysis, this task is associated with the development of new generic catalytic modes of action, induction and reactivity.
Our approach for developing novel reactivity in this field was based on combining asymmetric aminocatalysis with the principle of vinylogy, which allowed to functionalize a carbonyl compound at remote positions. Key to success was the ability of the amine catalyst to propagate the electronic effects inherent to aminocatalytic reactivity modes (i.e. the HOMO-raising and the LUMO-lowering activating effects) through the conjugated π-system of poly-unsaturated carbonyls while transmitting the stereochemical information at distant positions.
In chapter II, is developed an asymmetric vinylogous aldol reaction for the direct γ-functionalization of unsaturated carbonyl compounds using a bifunctional primary amine-thiourea catalyst that can combine H-bond-directing activation of the electrophile with the dienamine activation of enones to ensure high levels of enantio- and regio-selectivity.
n chapter III, the potential of organocascade catalysis is expanded by including vinylogous reactivity as a design principle for realizing unprecedented asymmetric domino reactions, a three component domino process proceeds by way of an amino-catalyzed Michael addition/1,6-addition/vinylogous aldolization sequence which combines two intermolecular and one intramolecular bond-forming events while forging six contiguous stereogenic centers with high fidelity. Key to this study was the ability to control the γ-site-selectivity of an asymmetric1,6-addition to linear 2,4-dienals, which was achieved by positioning a directing group within the β-dienal architecture.
In chapter IV, an enantioselective radical conjugate addition of enones by trapping photochemically generated carbon-centered radicals using iminium ion activation. Merging the ability of iminium ion catalysis to activate α,β-unsaturated ketones with the tendency of light-activated polyoxometalate catalysts to generate carbon-centered radicals under mild conditions was the tool for the development of this transfomation. This system contribute the first method for conducting asymmetric radical conjugate additions by means of iminium ion catalysis. This strategy expand the scope of enantioselective conjugate addition reactions promoted by asymmetric aminocatalysis. Until now, this type of transformation was restricted to polar reactivities (Michael reactions), using nucleophiles bearing easily deprotonable carbon atoms.
