SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES

本提案的目标是开发新的Fischer方法 用于有机合成的卡宾络合物 有希望的现有反应和有潜力的新反应。 这些 在此按其在提案中提出的顺序摘要说明。 我们将继续寻求新的和改进的环丙烷化方法 与Fischer卡宾络合物的反应。 将特别强调 给予不对称环丙烷化，合成helenalin，并 卡宾络合物与乙烯酮缩醛反应的新途径 为了生成高烯醇化物等价物，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 在与乙烯酮缩醛的反应研究中发现， 将探讨这一新反应的方法问题。 在异环化领域最突出的是 作为腈叶立德等价物的亚氨基络合物。 这是一个相对较新 一年前我们的实验室发现了这种反应，我们将 试图证明这些反应在合成 mesembrine，porphobilinogen，methoxatin，和第一个对映选择性 合成（-）-石斛碱。 其它卡宾络合物的杂环化将 以及尝试改善这些反应， 3-羟基吡啶合成。 在环己二烯酮成环领域， 的互变异构体被捕环化已经开发，这些将是 应用于灵芝酸B和D的合成。我们还将寻求 紫杉二酮的Diels-Alder/苄环化串联合成法 和罗立酮。 一个新的领域是非对称环的发展 通过首次制备手性恶唑烷酮卡宾 配合物 研究将被导向定义第一不对称的范围 卡宾配合物的Michael反应，并提出它们是 应用于（-）-石斛碱的合成。 卡宾络合物是 在不对称Aldol和Michael反应中的应用 包括吡咯烷络合物，新制备的恶唑烷酮络合物 以及迄今未知的咪唑啉酮络合物。 后两者可能 被认为是特别有利的， 通过与金属中心的内部螯合作用在构象上受到限制。 将继续对最近启动的项目进行调查 分子内和反电子需求Diels-Alder反应 Fischer卡宾络合物，特别是关于合成 吲哚生物碱 第一个成功的对映选择性Diels-Alder 卡宾络合物与作为手性助剂的薄荷醇的反应将是 追求的目标是开发薄荷醇作为一种有用的手性助剂 并找到解决非过渡金属Diels-Alder限制的方法， 反应. 这些Diels-Alder反应将应用于合成 紫杉二酮、罗勒酮和灵芝酸。 的可能性 亚氨基卡宾络合物的杂原子Diels-Alder反应也将 研究了 金属离子介导的交叉共轭烯酮的双环化反应， 最近在我们的实验室里发现了这种反应， 关于独脚金醇合成的范围和应用。

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.