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

对映选择性阴离子结合催化中的手性点击三唑：杂芳族化合物的脱芳构化

• 批准号: 263165479
• 负责人: Professorin Dr. Olga Garcia Mancheno
• 金额: --
• 依托单位: Organisch-Chemisches Institut
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/263165479?language=en
• 关键词: Chiral; Click; Triazoles; Enantioselective; Anion

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.

本项目将重点设计和开发基于三唑的手性结构，作为结构新颖的氢键供体阴离子结合催化剂，用于杂芳烃化合物的对映选择性脱芳化。杂环芳烃的脱芳化在学术界和工业界都是直接修饰环体系的重要方法，可以将简单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，尽管采用脱芳化技术生成具有合成价值的手性n和o杂环具有很大的潜力，但催化不对称工艺仍然非常具有挑战性和罕见。在本项目中，N-和o -杂芳烃化合物的不对称脱芳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。在初步研究中，将合成手性三唑催化剂，并将其用于触发和控制不对称反应，以异喹啉和吡啶为底物，硅酮缩醛为亲核试剂。该方法将推广到其他含二氮和含氧的杂芳烃。此外，用有价值的小亲核试剂如氰化物、叠氮化物或重氮甲烷三甲基硅基衍生物进行高要求的对映选择性脱芳化反应将受到挑战。该项目还旨在更好地了解所提出的三唑基催化剂的结构和性能，以及它们与阴离子的配合物，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。所获得的信息将用于重新设计新的催化剂，然后在目标脱芳反应中评估其活性。通过这种活性交联的方法，为这类新型阴离子结合催化剂的结构-反应关系提供了重要的信息。