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

本项目将致力于手性三唑类结构的设计和开发，作为结构新颖的氢键供体阴离子结合催化剂，用于杂芳烃的对映体选择性脱芳构化反应。杂芳烃的脱芳构化在学术界和工业界都是直接修饰环系的重要方法，可以将简单的结构转化为具有附加值的复杂分子。手性杂环是广泛存在于各种天然和合成生物活性分子中的关键结构单元。然而，尽管利用脱芳构化技术来合成有价值的手性N-和O-杂环的潜力很大，但催化不对称过程仍然非常具有挑战性和稀有。在这个项目中，N-和O-杂芳烃的不对称脱芳构化反应将导致重要的中间体或具有潜在生物活性的手性杂环化合物。在初步研究中，手性三氮唑基催化剂将被用来引发和控制以(Iso)喹啉和吡啶为底物，以硅酮缩醛为亲核剂的不对称反应。该方法将推广到其他含氮和含氧的杂芳烃。此外，使用氰化物、叠氮化合物或重氮甲烷三甲基硅基衍生物等有价值的小亲核剂进行高要求的对映选择性脱芳烃将面临挑战。该项目还旨在更好地了解所建议的三氮唑基催化剂及其与阴离子的络合物的结构和性能，以确定改进的高活性结构。为此，将采用几种现代分析方法和技术。获得的信息将用于重新设计新的催化剂，然后在目标脱芳构化反应中对其活性进行评估。通过这种活泼的交叉方法，旨在提供这一新的阴离子结合催化剂家族的结构与反应活性关系的重要信息。

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.