METAL CATALYZED CARBON-CARBON FORMING REACTIONS

医药活性化合物的全合成是 在生物医学科学领域的重要追求。 符合 我们对生物活性物质的有效全合成的兴趣 天然产品，我们正在进行一项研究计划， 发展新的碳-碳键结构 反应. 这些反应将简化碳的组装 各种天然产物中的骨架。 拟议的研究专门检查分子内 铁（O）催化的（4+2）-和（4+4）-烯反应， 正在成为编制《生物多样性公约》 官能化的碳环和杂环体系。 的 研究中的反应包括铁（O）催化的烯 将1，3-二烯偶联到2-取代的丙烯酸酯上， 烯丙基醚 这些底物的环化进行， 区域和立体化学控制的新方面。 特别是 这些反应以异常水平的立体诱导进行 并定义了一种新的不对称合成碳的策略， 和杂环系统。 在此期间，我们建议继续我们的研究 这些非常成功的碳环化反应。 我们的目标是 通过铁介导的立体选择性 合成，关键环系统，这是共同的亚基内的 生物活性天然产物的结构。 具体 我们提出的研究目的是使用催化铁介导的 碳环化反应以：1）实现立体选择性的 高度官能化5-和6-元环的合成 碳环，5-和6-元环氧-和氮- 杂环和中环系统; 2）完成 常见稠合双环系统的立体选择性合成; 3） 制备手性非外消旋碳环和杂环 系统在立体控制的方式，通过使用 可回收的手性助剂4）为新的，但 机械相关的碳环化反应;以及5） 详细了解金属依赖反应的起源 选择性。

The total syntheses of medicinally active compounds are important pursuits in the field of biomedical science. In line with our interest in the efficient total synthesis of biologically active natural products, we are pursuing a program of research directed toward the development of new carbon-carbon bond construction reactions. The reactions will simplify the assembly of the carbon backbone in a variety of natural products. The proposed research specifically examines intramolecular iron(O) catalyzed (4+2)- and (4+4)-ene reactions, which are emerging as valuable new methodologies for the preparation of functionalized carbo- and heterocyclic ring systems. The reactions under investigation include the iron(O) catalyzed ene coupling of 1,3-dienes to 2-substituted acrylate esters and to allylic ethers. The cyclizations of these substrates proceed with novel aspects of regio- and stereochemical control. In particular these reactions proceed with exceptional levels of stereoinduction and define a new strategy for the asymmetri synthesis of carbo- and heterocyclic ring systems. Under the period of this grant we propose to continue our studies on these highly successful carbocyclization reactions. Our goal is to make accessible, through iron-mediated stereoselective synthesis, key ring systems which are common subunits within the structures of biologically active natural products. The specific aims of our proposed research are to use catalytic iron-mediated carbocyclization reactions to: 1) accomplish the stereoselective synthesis of highly functionalized 5- and 6-membered ring carbocycles, 5- and 6-membered ring oxygen- and nitrogen- heterocycles, and medium-ring systems; 2) accomplish the steroselective synthesis of common fused-bicyclic ring systems; 3) prepare chiral non-racemic carbocyclic and heterocyclic ring systems in a stereocontrolled fashion through the use of recoverable chiral auxiliaries 4) defined substrates for new, but mechanistically related, carbocyclization reactions; and 5) understand in detail the origins of metal-dependent reaction selectivities.