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.

该提案的目标是开发费歇尔的新方法 卡宾配合物在有机合成中的应用 现有的反应有希望，新的反应有潜力。 这些 此处按其在提案中的呈现顺序进行了总结。 我们将继续寻求新的和改进的环丙烷化方法 烯烃与费歇尔卡宾配合物。 将特别强调的是 给予不对称环丙烷化，海伦那林的合成，以及 卡宾配合物与乙烯酮缩醛反应的新方法 用于生成同烯醇等价物、乙烯基卡宾等价物， 和三亚甲基甲烷当量。 新的C-H插入反应是 在与乙烯酮缩醛的反应研究中发现 将探讨这种新反应的方法学方面。 异环化领域最突出的是 亚氨基络合物作为腈叶立德等价物。 这是一个相对较新的 大约一年前在我们的实验室发现了反应，我们将 尝试证明这些反应在合成中的效用 松叶菊碱、胆色素原、甲氧沙丁和第一个对映选择性 合成(-)-石斛碱。 其他卡宾配合物的异质环化将 正在探索并尝试改善这些反应 3-羟基吡啶的合成。 在环己二烯酮成环区域选择性版本领域 的互变异构体阻滞环化已经开发出来，这些将是 应用于灵芝酸B和D的合成。我们也将追求 串联 Diels-Alder/苯环化法合成紫杉二酮 和罗伊兰酮。 一个新领域是不对称环的发展 首次制备手性恶唑烷酮卡宾使之成为可能 复合物。 研究将旨在定义第一个不对称的范围 卡宾配合物的迈克尔反应，建议它们是 应用于(-)-石斛碱的合成。 卡宾配合物为 评估其在不对称羟醛反应和迈克尔反应中的作用 包括吡咯烷配合物、新制备的恶唑烷酮配合物 以及迄今为止未知的咪唑啉酮配合物。 后两者可以 被认为是特别有利的，因为手性助剂是 构象上受到金属中心的内部螯合限制。 将继续对最近启动的计划进行调查 分子内和逆电子需求狄尔斯-阿尔德反应 费歇尔卡宾配合物特别是在合成方面 吲哚生物碱。 第一个成功的对映选择性 Diels-Alder 卡宾配合物与薄荷醇作为手性助剂的反应为 追求的目标是开发薄荷醇作为有用的手性助剂 并寻找解决非过渡金属 Diels-Alder 局限性的解决方案 反应。 这些 Diels-Alder 反应将应用于合成 紫杉二酮、royleanone 和灵芝酸。 的可能性 亚氨基卡宾配合物的杂原子狄尔斯-阿尔德反应也将是 调查了。 金属介导的交叉共轭烯酮双环化反应为 我们的实验室最近发现了这一反应，并将对其进行研究 关于三甘醇合成的范围和应用。