SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES

拟议工作的主要目标之一是开发非对称 手性咪唑啉酮卡宾络合物的反应。 这些复合物 将在羟醛缩合反应中用作手性乙酸酯等价物， 炔醛类化合物在合成抗癌新药福司曲星中的应用 人体临床试验的第一阶段观察到的不寻常的立体化学 与炔醛的羟醛缩合反应可能是由于底物可定向 羟醛缩合反应 提出实验来测试这一点，并确定是否 直接羟醛缩合反应可以与除了 炔。早期的结果表明，咪唑啉酮卡宾配合物 在它们的Diels-Alder反应中是外选择性的，因此一般研究 提出了研究这些反应的范围和机制。的 这些配合物的迈克尔加成也将在以下情况下进行研究， 手性卡宾络合物既用作迈克尔受体， 供体 提出了应用于合成甲基炔诺酮和 石斛碱 Fischer卡宾配合物的环丙烷化反应 将探索合成环丙酮的新方法 缩醛和用于不对称合成helenalin和环丙烷 个氨基酸 还探索了一种合成5-羟基-2-甲基-3-（4-甲氧基苯基）-2-甲基-2-（4-甲氧基苯基）-2-（4-甲氧基苯基 由金属介导的Bergman型环化得到羟基吲哚。 计划 概述了几个卡宾的不对称反应的发展 与包括不对称苯并环化的炔的络合物， 环己二烯酮的不对称合成和环己二烯酮的不对称合成 联芳基 与手性炔丙基胺的不对称苯并环化反应， 提出作为合成M（5-7）三肽部分的关键步骤 万古霉素最后，研究了手性卡宾配合物与 本文将研究炔类化合物在氢化茚酮不对称合成中的应用 衍生物和三环和双环内酯。

One of the major goals of the proposed work is to develop the asymmetric reactions of chiral imidazolidinone carbene complexes. These complexes will be utilized as chiral acetate equivalents in aldol reactions with alkynals in the synthesis fostriecin, a new anti cancer drug that Is in phase I of human clinical trials. The unusual stereochemistry observed in the aldol reactions with alkynals may be due to a substrate directable aldol reaction. Experiments are proposed to test this and to determine if directable aldol reactions are possible with functional groups other than alkynes. Early results reveal that the imidazolidinone carbene complexes are exo selective in their Diels-Alder reactions and thus a general study is proposed to examine the scope and mechanism of these reactions. The Michael additions of these complexes will also be studied in cases where the chiral carbene complex is to serve both as the Michael acceptor and donor. Applications are proposed for the synthesis of methynolide and dendrobine. The cyclopropanation reactions of Fischer carbene complexes will be investigate for new methods for the synthesis of cyclopropanone acetals and for the asymmetric synthesis of helenalin and cyclopropane amino acids. Also to be explored is a new method for the synthesis of 5- hydroxyindoles from a metal-mediated Bergman type cyclization. Plans are outlined for the development of several asymmetric reactions of carbene complexes with alkynes which include asymmetric benzannulations, asymmetric synthesis of cyclehexadienones and asymmetric synthesis of biaryls. The asymmetric benzannulations with chiral propargyl amines is proposed as the key step in a synthesis of the M(5-7) tripeptide portion of vancomycin. Finally, the reactions of chiral carbene complexes with alkynes will be investigated for the asymmetric synthesis of hydrindenone derivatives and tri- and bicyclic lactones.