TRANSITION METAL CATALYZED C-C BONDING FORMING REACTION

（申请人的摘要）合成有机化学继续 在优化生物活性的治疗活性方面发挥主导作用， 活跃的结构。我所在小组的研究方向是 新型催化过渡金属介导的碳-碳键形成反应 应用于不饱和底物的碳环化。我们的目标是 提供了用于有机合成的新的环化方法， 常见的有机官能团，并在金属中进行催化。来约会我们的 方法已经解决了环化的两个机制方面， 以及新方法的非常简单的合成应用。现有 资助期标志着从方法学向综合方法学的过渡 应用.此次竞争性续约申请延续了这一举措。上 根据先前完成的发现和开发工作， 在NIH的支持下，有一个很好的无障碍环系统调查， 耐受的官能度和立体化学控制， 铁催化的烯二烯碳环化和钯催化的双二烯 碳环化我们现在把重点放在更有针对性的问题， 药物相关分子。该提案的具体目的是 证明了这些新的债券结构作为战略层面的可行性 复杂分子的全合成反应。目标包括A80577， 前列腺素类布雷菲德菌素和类固醇。他们的合成是为了利用 独特的结构和有机金属中间体的反应性，以控制 立体化学和区域化学过程，但 不仅仅是我们现在所知的化学的应用。每个应用被 旨在推动金属介导的环化方法的极限， 因此，需要有针对性的发展工作才能取得成功。

DESCRIPTION: (Applicant's Abstract) Synthetic organic chemistry continues to play a dominant role in optimizing the therapeutic-activity of biologically active structures. Research in my group is directed toward the development of novel catalytic transition-metal-mediated carbon-carbon bond forming reactions applied to the carbocyclization of unsaturated substrates. Our goal is to provide novel cyclization methodologies for organic synthesis that utilize common organic functional groups and proceed catalytic in metal. To date our approach has been to address both mechanistic aspects of the cyclizations as well as very simple synthetic applications of the new methods. The prior funding period marked a transition away from methodology and toward synthetic applications. This competitive renewal application continues that move. On the basis of the discovery and developmental work that was completed under prior NIH support there is a good survey of the accessible rings systems, functionalities tolerated and the stereochemical control in both the iron-catalyzed enediene carbocyclizations and the palladium-catalyzed bisdiene carbocyclizations. We now focus more targeted problems in the synthesis of pharmaceutically relevant molecules. The specific aim of the proposal is to demonstrate the viability of these novel bond constructions as strategy-level reactions for complex molecule total synthesis. The targets include A80577, prostanoids, brefeldin, and steroids. Their syntheses are designed to exploit the unique structure and reactivity of organometal intermediates to control the stereochemical and regiochemical course of carbon-carbon bond construction, but are not simply applications of chemistry we now know. Each application is designed to push the limits of the metal-mediated cyclization methodology, and as such will require targeted developmental work to be successful.