METAL CATALYZED CARBON-CARBON FORMING REACTIONS

药用活性化合物的合成方法如下： 在生物医学科学领域的重要追求。与…一致 我们对生物活性高效全合成的兴趣 天然产品，我们正在进行一项有针对性的研究计划 走向新型碳-碳键结构的发展 反应。这些反应将简化碳的组装 脊椎中含有多种天然产品。 这项拟议的研究专门研究了分子内 铁(O)催化的(4+2)-和(4+4)-烯反应，它们是 正在成为有价值的新方法，用于编制 官能化碳环和杂环体系。这个 正在研究的反应包括铁(O)催化的烯 1，3-二烯与2-取代丙烯酸酯的偶联反应 烯丙基醚。这些底物的环化反应继续进行。 区域和立体化学控制的新方面。特别是 这些反应伴随着超常水平的立体诱导。 并为碳的不对称合成定义了新的策略。 和杂环环体系。 在这笔赠款的期限内，我们打算继续我们的学业 关于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使人容易接近 合成，密钥环系统，是 生物活性天然产物的结构。具体的 我们提议的研究的目的是使用催化铁介体 碳环化反应：1)完成立体选择性 高官能化五元环和六元环的合成 碳环，5元和6元环氧和氮- 杂环和中环体系；2)完成 常用稠合双环体系的立体选择性合成；3) 手性非外消旋碳环和杂环的制备 系统以一种固定的控制方式通过使用 可回收的手性助剂4)定义了新的，但是 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.