NEW METHODS FOR STEREOSELECTIVE ADDITIONS TO CARBONYLS

描述：(首席研究人员摘要)药物化学家依靠 关于有机合成工具，以制备新的治疗剂，或 制备分子研究现有治疗药物的作用机制 探员们。鉴于手性在药物生物活性中的重要性， 药物化学家需要制备对映体和对映体的方法 非对映异构体纯分子。这笔拨款支持一项研究计划， 其目的是发现新的立体选择性和化学选择性反应 以及有机合成中的试剂。机械论有机化学的工具 用于研究选择性试剂和催化剂的作用机理。 这些研究的结果随后被用来设计新的试剂和催化剂。 这提供了比原始版本更好的性能。在这项提案中，延续了 酮和丙酮对映体选择性还原剂的开发工作 描述了使用手性Ru络合物的醛。这些产品的使用 手性α-和β-烷氧基醛的动力学拆分 将对酮进行研究。描述了第二手性还原剂，其 是基于上一个供资期间所做的工作，其中 具有不同结合和催化中心的羟基定向催化剂 并对其机理进行了研究。这种还原剂是从 烷氧基定向的Corey-Bakshi-Shibata(CBS)催化剂 通过结合结合部位。正如在Ru衍生体系中一样， 手性α-和β-烷氧基醛和酮的动力学拆分 用这种催化剂进行研究。此外，跳过的1，3，5-三醇的合成将 这种化学的应用是为了合成 抗真菌药霉菌素。第二个项目涉及乙烯基材料的使用 离子Diels-Alder反应中的氧卡宾离子。这个正在进行的项目 重点研究该反应的立体选择性，特别是在 可以显示远程不对称感应的系统。最后，综合 使用卤素舞蹈的变体和新的 对发现的锡舞反应进行了描述。

DESCRIPTION: (Principal Investigator's Abstract) The medicinal chemist relies on the tools of organic synthesis to prepare new therapeutic agents, or to prepare molecules to study the mechanism of action of existing therapeutic agents. Given the importance of chirality in the biological activity of drugs, medicinal chemists need methods for the preparation of enantiomerically and diastereomerically pure molecules. This grant supports a research program the aims of which are to discover new stereoselective and chemoselective reactions and reagents in organic synthesis. The tools of mechanistic organic chemistry are used to study the mechanism of action of selective reagents and catalysts. The results of these studies are then used to devise new reagents and catalysts that offer advantages over the original. In this proposal, a continuation of work on the development of enantioselective reducing agents for ketones and aldehydes using chiral ruthenium complexes is described. The use of these complexes in the kinetic resolution of chiral alpha- and beta-alkoxy aldehydes and ketones will be studied. A second chiral reducing agent is described that is based on work undertaken in the last funding period wherein hydroxyl-directed catalysts which bear separate binding and catalytic sites were designed and their mechanisms studied. This reducing agent is derived from the Corey-Bakshi-Shibata (CBS) catalyst which has been rendered alkoxy-directed by the incorporation of a binding site. As in the ruthenium derived system, the kinetic resolution of chiral alpha- and beta-alkoxy aldehydes and ketones will be studied with this catalyst. Also, the synthesis of skipped 1,3,5-triols will be undertaken, the application of this chemistry being to the synthesis of the antifungal agent mycoticin. A second project relates to the use of vinyl oxocarbenuim ions in the ionic Diels-Alder reaction. This ongoing project focuses on studying the stereoselectivity of this reaction, especially in systems which can display remote asymmetric induction. Finally, the synthesis of substituted heterocycles using variants of the halogen dance and the newly ,discovered tin dance reaction is described.