Catalytic Methods and Cascade Processes in Organic Synthesis

我们希望在合成、使用新型活性中间体及其独特的成键反应性方面发明并应用新的、策略级别的转化。这项研究的成功实施将揭示构建在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这些中间体的反应性的新知识。我们建议的工作分为三个主要领域。第一个涉及周环反应，称为纳扎罗夫环化。这一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一个有吸引力的候选者。此外，我们希望能够通过仔细设计起始化合物来利用新型的额外成键反应(“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。第二个项目涉及使用催化生成的金属卡宾形成瞬时杂环中间体，这些中间体可用于合成几种具有重要医学意义的天然产品。这些反应也可能服从不对称催化。包括一个涉及金属卡宾-叠氮化物偶联反应的非常新的领域。最后，我们计划开发基于具有内部捕获基团的高应变环烯的生成的新化学。这项工作包括多步合成、广泛的反应优化和结构确定。因此，预计它将为高素质人才的培训提供良好的环境。

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.