Chiral Click-Triazoles in Enantioselective Anion-Binding Catalysis: Dearomatization of Heteroaromatic Compounds

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The here proposed project will be focused on the design and development of chiral triazole-based structures as structurally novel H-bond donor anion-binding catalysts for the enantioselective dearomatization of heteroaromatic compounds. The dearomatization of heteroarenes constitutes an important approach, in both academia and industry, for the direct modification of the ring system, allowing the conversion of simple structures into complex molecules of added value. Chiral heterocycles are widely occurring key structural units in a variety of natural and synthetic bioactive molecules. However, and despite the high potential of employing the dearomatization technique to generate synthetically valuable chiral N-and O-heterocycles, catalytic asymmetric processes are still very challenging and rare. In this project, asymmetric dearomatization reactions of N- and O-heteroaromatic compounds that lead to important intermediates or chiral heterocylces with interesting potential bioactivity will be pursued. In preliminary studies, chiral triazole-based catalysts will be synthesized and employed to trigger and control asymmetric reactions implying (iso)quinolines and pyridines as substrates and silyl keten acetals as nucleophiles. The methodology will be extended to other dinitrogen- and oxygen-containing heteroarenes. Additionally, highly demanding enantioselective dearomatizations with valuable small nucleophiles such as cyanide, azide or diazomethane trimethylsilyl derivatives will be challenged. This project also aims at a better understanding of the structure and performance of the proposed triazole-based catalysts as well as their complexes with anions in order to identify improved highly active structures. For that reason, several modern analytical methods and techniques will be employed. The information obtained will be used to re-design new catalysts, whose activity will be then evaluated in the targeted dearomatization reactions. With this living intercrossing approach intends to provide important information of the structure - reactivity relationship of this new family of anion-binding catalysts.