Conjugate additions and organocatalytic sequential reactions - new approaches to old reactions
Abstract
This thesis consists in a collection of projects wherein the focus is
the application of organocatalysts to accelerate the reactions, its primary function,
as to induce asymmetry to the synthetic targets, within a perspective of sustainable
chemistry.
Thus, this thesis was arranged in four sections, the first two being
about conjugate additions reactions; the third one related to 1,6-Friedel-Crafts/
1,4-oxa-Michael cascade, and finally the fourth related to a formal [3 + 3]
cycloaddition reaction.
The first chapter describes the application of ionic liquids as basic
catalysts in the conjugate addition of diketones to nitroolefins irradiated by
ultrasound. Thus, the Michael adducts, which are important synthetic building
blocks were synthesized efficiently under solvent free conditions. In the second chapter is presented the formal synthesis of Pregabalin
Phenibut and Bacoflen. The synthetic intermediate of theses are obtained via a
conjugate addition of aldehydes to nitroolefins, using an organocatalyst developed
by our group in PEG-400, as recyclable solvent. In this regard, a collection of
Michael adducts was synthesized within the principles of green chemistry in good
yields and selectivities. The third section describes the first organocatalytic asymmetric
cascate 1,6- Friedel-Crafts / 1,4- Oxa-Michael of hydroxyarenes to 2,4-dienal for
the construction of chiral chromans, which are important bioactive compounds. A
collection of chiral chromans was synthesized with high yields and selectivities
(94-99% ee). Furthermore, several manipulations were made including the
formation of a macrocyclic lactam. Finally, the fourth section dedicated to the formal [3 + 3]
cycloaddition of azomethine imine with methyl isocyanoacetates leading to 1,2,4
triazines derivatives, which are relevant biological activity heterocyclic. We used
either organocatalytic approach as cooperative catalysis (organocatalysis and
metal catalysis). This work is still in the primary stages, however the product has
been obtained with up to (42% ee, 69% yield), as just one diastereomer.