Catalytic Methods and Cascade Processes in Organic Synthesis

有机合成中的催化方法和级联过程

• 批准号: 249822-2013
• 负责人: West, Frederick
• 金额: $ 6.12万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632810
• 关键词: Catalytic; Methods; Cascade; Processes; Organic

We wish to invent and apply new, strategy-level transformations in synthesis, using of novel reactive intermediates and their unique bond-formation reactivity. Successful implementation of this research will unveil new ways to build the complex structures found in many bioactive natural products. Importantly, this work will also generate new knowledge about the reactivity of these intermediates by examining their behaviour in complex molecular frameworks. Our proposed work is divided into three main areas. The first concerns the pericyclic reaction known as the Nazarov cyclization. The manner in which this process establishes new stereocentres in the products makes it an attractive candidate for asymmetric catalysis. Moreover, we expect to be able to leverage new types of additional bond-forming reactivity ("interrupted Nazarov" reactions) through careful design of the starting compounds. The resulting "domino" processes will permit the very rapid build up of molecular complexity using simple starting materials. The second project involves the use of catalytically generated metallocarbenes to form transient heterocyclic intermediates, which can be used in the synthesis of several medically important natural products. These reactions may also be amenable to asymmetric catalysis. Included is a very new area involving metallocarbene-azide coupling reactions. Finally, we plan to develop new chemistry based upon the generation of highly strained cyclic allenes that possess an internal trapping group. This work entails multistep synthesis, extensive reaction optimization, and structure determination. As a result, it is expected to offer an excellent environment for the training of highly qualified personnel.

我们希望在合成中发明和应用新的战略级转化，使用新的活性中间体及其独特的成键反应性。这项研究的成功实施将揭示构建许多生物活性天然产品中发现的复杂结构的新方法。重要的是，这项工作还将通过检查这些中间体在复杂分子框架中的行为来产生关于它们的反应性的新知识。我们建议的工作分为三个主要领域。第一个涉及被称为Nazarov环化的周环反应。该过程在产物中建立新的立体中心的方式使其成为不对称催化的有吸引力的候选者。此外，我们期望能够通过仔细设计起始化合物来利用新类型的额外成键反应性（“中断的纳扎罗夫”反应）。由此产生的“多米诺骨牌”过程将允许使用简单的起始材料非常快速地建立分子复杂性。第二个项目涉及利用催化生成的多碳烯形成短暂的杂环中间体，可用于合成几种重要的医学天然产品。这些反应也可以适用于不对称催化。其中包括一个非常新的领域，涉及双卡宾-叠氮化物偶联反应。最后，我们计划开发新的化学基础上产生的高度紧张的环状联烯，具有内部捕获组。这项工作需要多步合成，广泛的反应优化和结构测定。因此，预计它将为培养高素质人才提供一个良好的环境。