SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES

卡宾配合物的合成应用

• 批准号: 3283505
• 负责人: WILLIAM Dean WULFF
• 金额: $ 21.68万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283505
• 关键词: Diels Alder reaction; alkaloids; alkenes; alkyl nitrile; carbene; chelating agents; chemical synthesis; cyclization; imidazolidone; iminoacid; indoles; ketene; metal complex; organic chemicals; porphobilinogen; transaldolase /transketolase

The goal of this proposal is to develop new methodologies of Fischer carbene complexes for applications to organic synthesis concentrating on existing reactions with promise and new reactions with potential. These are summarized here in the order of their presentation in the proposal. We will continue to seek new and improved methods for the cyclopropanation of olefins with Fischer carbene complexes. Particular emphasis will be given to asymmetric cyclopropanations, the synthesis of helenalin, and to the reaction of carbene complexes with ketene acetals for new approaches for the generation of homo-enolate equivalents, vinyl carbene equivalents, and trimethylene methane equivalents. New C-H insertion reactions were discovered in the study of the reactions with ketene acetals and methodological aspects of this new reaction will be explored. Most prominent in the area of heteroannulation is the development of imino complexes as nitrile ylide equivalents. This is a relatively new reaction discovered in our laboratories about a year ago and we will attempt to demonstrate the utility of these reactions in the synthesis of mesembrine, porphobilinogen, methoxatin, and the first enantioselective synthesis (-)-dendrobine. Heteroannulation of other carbene complexes will be explored as well as attempts to improve these reactions for the synthesis of 3-hydroxypyridines. In the area of cyclohexadienone annulations regioselective versions of the tautomer arrested annulation have been developed and these will be applied to the synthesis of ganoderic acids B and D. We will also pursue a tandem Diels-Alder/benzannulation approach to the synthesis of taxodione and royleanone. A new area is the development of asymmetric annulations made possible by the first preparation of chiral oxazolidinone carbene complexes. Studies will be directed to define the scope of the first asymmetric Michael reactions of carbene complexes and it is proposed that they be applied to the synthesis of (-)-dendrobine. Carbene complexes to be evaluated for there service in asymmetric aldol and Michael reactions include pyrrolidine complexes, the newly prepared oxazolidinone complexes and the as of yet unknown imidazolidinone complexes. The latter two may be considered particularly advantageous since the chiral auxilliary is conformationally restricted by internal chelation to the metal center. Investigations will continue on the more recently initiated programs of intramolecular and inverse-electron demand Diels-Alder reactions of Fischer carbene complexes particularly with regard to the synthesis of indole alkaloids. The first successful enantioselective Diels-Alder reaction of carbene complexes with menthol as chiral auxilliary will be pursued with the goal of developing menthol as a useful chiral auxilliary and to finding solutions to limitations in non-transition metal Diels-Alder reactions. These Diels-Alder reaction will be applied to the synthesis of taxodione, royleanone, and the ganoderic acids. The possibility of heteroatom Diels-Alder reactions of imino carbene complexes will also be investigated. The metal mediated double-cyclization of cross-conjugated ketenes was recently discovered in our laboratories and this reaction will be studied with regard to scope and application to the synthesis of strigol.

该建议的目的是开发Fischer的新方法论 用于施用有机合成的碳烯络合物集中于 现有的反应具有承诺和潜力的新反应。 这些 在此处以其在提案中的介绍顺序汇总。 我们将继续寻求环环植物的新方法和改进的方法 带有Fischer Carbene复合物的烯烃的烯烃。 特别强调将是 给出了不对称环丙旋植物的合成，helenalin的合成和 碳烯络合物与酮乙烯的反应对新方法的反应 为了产生同型等效物，乙烯基碳烯等效物， 和三甲基甲烷当量。 新的C-H插入反应是 在研究与酮乙烯的反应的研究中发现 将探讨这种新反应的方法论方面。 在异质化领域最突出的是发展 Imino复合物作为氮化物等效物。 这是一个相对较新的 大约一年前在我们的实验室中发现的反应，我们将 尝试证明这些反应在合成中的效用 梅堡，卟啉原，甲氧蛋白和第一个对映选择性 综合（ - ） - 树突状。 其他卡宾综合体的杂汁将 探索以及试图改善这些反应 3-羟基吡啶的合成。 在环己酮环境环境区域选择版本中 已经开发了互变异剂的逮捕环，这些将是 应用于Ganoderic酸B和D的合成。我们还将追求 串联Diels-Alder/横向方法用于合成Taxodione 和royleanone。 一个新区域是不对称环境的发展 通过第一次制备手性黄唑啉酮卡宾使之成为可能 复合物。 研究将定义第一个不对称的范围 迈克尔对卡宾综合体的反应，并提议它们是 应用于（ - ） - 树突状的合成。 卡宾综合体为 评估在不对称藻和迈克尔反应中的服务 包括吡咯烷络合物，新制备的黄唑啉酮配合物 以及尚不清楚的咪唑啉酮复合物。 后两个五月 由于手性辅助是 构象受到内部螯合的限制。 调查将继续对最近发起的计划进行 分子内和反电子的需求双向alder-alder-alder反应 Fischer Carbene配合物，特别是关于合成的 吲哚生物碱。 第一个成功的对映选择性Diels-alder 卡宾络合物与薄荷醇作为手性辅助的反应将是 追求将薄荷醇作为有用的手性辅助的目标 并找到解决非转变金属Diels-alder限制的解决方案 反应。 这些Diels-Alder反应将应用于合成 Taxodione，royleanone和Ganoderic酸。 可能的可能性 Imino Carbene综合体的杂原子Diels-Alder反应也将是 调查。 跨缀合的酮的金属介导的双环化为 最近在我们的实验室中发现，将研究这种反应 关于范围和应用于斯特里戈尔的合成。