SYNTHETIC APPLICATIONS OF CARBENE COMPLEXES

拟议工作的主要目标之一是开发不对称 手性咪唑烷酮卡宾络合物的反应。这些复合体 将在羟醛缩合反应中用作手性醋酸酯的等价物 一种新的抗癌药物Fostriecin的合成中的炔类化合物 人类临床试验的第一阶段。观察到的不同寻常的立体化学 与炔醛的羟醛反应可能是由于底物可定向的。 羟醛反应。建议进行实验来测试这一点，并确定 可直接的羟醛缩合反应可以与官能团 乙炔。早期结果表明，咪唑烷酮卡宾络合物 在Diels-Alder反应中是外向选择性的，因此是一项一般性的研究 建议研究这些反应的范围和机制。这个 这些络合物的Michael加成也将在以下情况下进行研究 手性卡宾络合物既作为Michael受体又作为Michael受体 捐赠者。提出了其在合成甲基内酯和甲基内酯方面的应用。 石冠菊。Fischer卡宾络合物的环丙烷化反应 将研究合成环丙酮的新方法 缩醛和不对称合成洋茉莉和环丙烷 氨基酸。此外，还将探索一种新的合成5-羟基-4-甲基-4-酮的方法。 金属介导的Bergman环化反应生成的羟基吲哚。计划是 卡宾的几种不对称反应的研究进展 含不对称苯环的炔类络合物， 环己二酮的不对称合成及环己二酮的不对称合成 联芳烃。手性炔丙胺的不对称苯环反应是 建议作为合成M(5-7)三肽部分的关键步骤 万古霉素。最后，手性卡宾络合物与手性卡宾的反应 乙炔类化合物将被用于不对称合成水杨二酮 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.