SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES

这项提案的目标是开发费舍尔的新方法论 卡宾配合物在有机合成中的应用 既有有希望的反应，也有有潜力的新反应。这些 现按其在建议书中的表述顺序进行总结。 我们将继续寻求新的和改进的环丙烷化方法 含Fischer卡宾络合物的烯烃。特别强调的是 用于不对称环丙烷化、洋茉莉素的合成和 卡宾配合物与烯酮缩醛反应的新途径 对于高烯醇类当量物、乙烯卡宾当量物的生成， 和三亚甲基甲烷当量。新的C-H插入反应是 在研究与烯酮缩醛的反应中发现的 将探讨这一新反应的方法学方面。 在异型环扎方面最突出的是 亚氨基络合物作为丁腈叶立德的等价物。这是一个相对较新的 大约一年前在我们的实验室中发现了这种反应，我们将 试图证明这些反应在合成化合物中的效用 中膜、胆红素原、甲氧西汀和第一对映体 合成(-)-树突罗宾。其他卡宾化合物的杂环化将 以及改善这些反应的尝试 3-羟基吡啶的合成。 在环己二烯酮环化领域区域选择版本 已经开发出互变异构体阻滞环，这些将是 应用于灵芝酸B和D的合成。我们还将继续 串联Diels-Alder/苯环法合成紫杉二酮 和罗伊利酮。一个新的领域是不对称环带的发展 首次制备手性恶唑烷酮卡宾 复合体。 研究的方向将是定义第一个不对称的范围 卡宾络合物的Michael反应，并提出它们是 应用于(-)-树突宾的合成。卡宾络合物为 在不对称Aldol和Michael反应中的应用评价 包括吡咯烷类化合物，新制备的恶唑烷酮类化合物 以及未知的咪唑烷酮络合物的AS。后两者可能 被认为特别有利，因为手性助剂是 构象受限于金属中心的内部络合作用。 将继续对最近启动的项目进行调查 分子内和逆电子需求的Diels-Alder反应 Fischer卡宾配合物，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 卡宾络合物与薄荷醇作为手性助剂的反应将是 追求将薄荷醇作为一种有用的手性助剂的目标 以及寻找非过渡金属Diels-Alder限制的解决方案 反应。这些Diels-Alder反应将被应用于合成 紫杉二酮、紫杉酮和灵芝酸。是否有可能 亚胺卡宾配合物的杂原子Diels-Alder反应也将被 调查过了。 金属催化的交联烯酮的双环化反应是 最近在我们的实验室发现了这种反应，并将对其进行研究 关于Strigol的合成的范围和应用。

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.