Organocatalytic Asymmetric Synthesis of Isochromanones, Tetranortriterpenoids and Pyrazolone Derivatives

This thesis explores the applications of organocatalysis and its combination with metal catalysis for the enantioselective synthesis of novel oxygen- and nitrogen-containing heterocycles. The developed procedures rely on both covalent- and hydrogen-bounding organocatalysis and metal coordination catalysis. The first project focused on the development of an efficient asymmetric synthesis of new 4-amino-isochromanones starting from anilines and 2-formylbenzoates. The imine-formation followed by a cis-selective 6-enolexo-exo-trig Mannich reaction catalysed by a tetrazole analogue of proline provided the potentially bioactive title heterocycles with good yields (up to 85%) and excellent stereoselectivities (dr up to 99:1, up to 99% ee). The second developed procedure involved a quadruple domino oxa-Michael/Michael/Michael/aldol reaction followed by a lanthanide catalysed IEDHDA reaction in a one-pot fashion for the synthesis of novel polyfunctionalised tetranortriterpenoids with high yields and excellent stereocontrol. The five reactions occurred smoothly to the formation of six bonds and six stereogenic centres starting from readily available and simple substrates. Furthemore, we investigated a novel desymmetrising cross-dehydrogenative coupling, which relies on an initial Michael addition followed by a combination of aromaticity and extensive conjugation driving to an oxidant- and metal-free hydride elimination. A series of new densely functionalised pyrazoles bearing a quaternary stereocenter were synthesised with high yield and good enantioselectivities. Lastly, the electrophilic reactivity of a series of novel pyrazole-4,5-dione derivatives in the organocatalytic Friedel-Crafts reaction with variously substituted indoles has been tested. The disclosed procedure catalyzed by a cinchona alkaloid derivative allows the conjugation of two very important aza-heterocyclic scaffolds to generate a new class of indolyl-pyrazolones bearing a quaternary stereocenter in excellent yields (up to 99%) and enantioselectivities (up to 88% ee)