Chiral organocatalysts mediated asymmetric oxyfunctionalization and tandem reaction

Abstract

Asymmetric organocatalysis is a new rapidly growing field whose huge potential is becoming more and more evident.This PhD project has been conceived and developed in the context of non-covalent organocatalysis. The aim of this work has been to design, plan and develop new organocatalytic methodologies for the synthesis of optically active, densely functionalized, organic molecules whose functional groups are susceptible to further manipulation. The target molecules represent important motifs present in many biologically active natural and non-natural substances. The catalysts used are small chiral organic molecules, in particular the attention has been focused on bifunctional organocatalysts. The main features of the catalysts are their non-toxicity, stability to air and moisture and the ability to work under mild conditions that make them convenient tools in organic chemistry. These promoters are able to synergistically activate both the electrophile and the nucleophile through multiple hydrogen-bonding interactions provided by their acid and basic groups with the reactive groups of the reagents. The best-performing chiral scaffold of the bifunctional organocatalysts, employed in the methodologies herein developed, has been selected screening the activity of previously reported promoters such as ureas, thioureas, squaramides, amino alcohols. However, the design and synthesis of new optically pure bifunctional organocatalysts, modifying the chiral backbone and by tuning their stereoelectronic features, has been one of the objectives of this doctoral project. The stereoselective construction of a quaternary stereocentre, especially when it is an all-carbon quaternary stereocentre, is one of the most difficult goals in organic synthesis due to the steric congestion imposed by the four attached substituents. In this project, the synthesis of challenging molecules, bearing quaternary stereocentres in their structure, has been accomplished... [edited by author]