Chiral heterocycles are ubiquitous structures in natural and synthetic molecules, but chemists are still struggling to develop general, convenient and mild methods for a direct synthesis of these products. Therefore, important work has been done in the field of anion-binding thiourea-catalyzed dearomatization reactions of heteroarenes by applying chiral thiourea catalysts. In this regard, the group of Olga García Mancheño developed a new class of triazole based C-H bond anion-binding catalysts. These catalysts were successfully applied into asymmetric dearomatization reactions of quinolines, isoquinolines and pyridines.
The main aim of this PhD was the development of novel asymmetric dearomatization reactions with the TetraTri catalysts showing their broad synthetic application spectrum.
In Chapter 2, the first anion-binding organocatalyzed enantioselective Reissert-type dearomatization of diazarenes has been developed. Due to various reactive sites in the diazarene structures, the reaction presents regioselectivity issues and is therefore highly challenging. Fortunately, the use of a chiral tetrakistriazole as a C–H-based hydrogen-donor catalyst allowed the straightforward highly regio- and enantioselective synthesis of a variety of chiral diazaheterocycles.
In Chapter 3, phosphorous nucleophiles were further explored. We could describe the first enantioselective synthesis of chiral heterocyclic α-amino phosphonates by nucleophilic dearomatization of quinolines and pyridines using an anion-binding organocatalysis approach. Chiral tetrakistriazoles were employed as efficient hydrogen-bond donor catalysts. The corresponding products were obtained in complete or high regioselectivities and up to 97:3 e.r. for quinolines or up to 87:13 e.r. for the more demanding pyridine substrates. This method allows the rapid access to substituted chiral cyclic α-amino phosphonates, which can easily further be transformed into phosphonic acid derivatives. Introducing boron-nucleophiles in the same reaction was not successful and did not lead to any new discovery.
In Chapter 4, we changed from the nitrogen-containing heteroarenes to the more challenging oxygen-containing heterocycles. A general and highly enantioselective catalytic synthesis of 2-alkyl substituted oxygen heterocycles by nucleophilic dearomatization of pyrylium triflate derivatives with silyl ketene acetals has been developed. The use of chiral triazoles as anion-binding catalysts, able to form a close ion-pair with the substrates, was crucial to achieve both high conversions and chirality transfer. Thus, this method provides a simple access to chiral chromanones and dihydropyranones in excellent enantioselectivities from the corresponding 4-(benzo)pyranones.
Besides the main theme of my thesis, in chapter 5 the project of my stay abroad at the Universidad Autonoma de Madrid was described. A novel intramolecular photocatalyzed enantioselective α-alkylation of aldehydes was developed, yielding the desired product in good yield and enantioselectivity. Due to reproducibility issues and a limited applicability of the substrate scope, no further investigations were done
