ARENE ACTIVATION BY TRANSITION METALS

该提案的广泛、长期目标是开发应用程序 芳烃-金属π配合物的全合成具有挑战性的 分子阵列是重要的天然产物的组成部分， 分子，并开发基于不对称合成的新方法 芳烃-金属的手性亲核加成反应 配合物 具体目标如下： (a)继续对芳烃的应用进行研究- Mn（CO）3和芳烃-RuCp阳离子在Ristoclavin A的全合成中， 一种与万古霉素和替考拉宁相关的复合糖肽， 其分子结构为生物学的发展提供了一个具有挑战性的机会， 开发新的和独特的方法来构建日记 具有敏感连接的氨基酸和肽官能团的醚。 糖肽靶点具有相当大的意义， 作为抗革兰氏阳性菌的抗生素活性。 (b)探索芳烃金属配合物在合成中的应用 对映体纯的4，5-二取代的环己烯酮和相关的 化合物，通过手性手性定向的不对称亲核试剂 添加到芳烃配体。 (c)铼促进的分子内二芳基醚的初步研究 形成，以及基于以下的季铵盐催化的二醇醚形成： 氯代芳烃-RuCp阳离子的化学计量反应的观察， 其允许被保护的氯芳基氨基酸与 保护的羟基芳基氨基酸和衍生的肽。 这些方法 允许容易地构建用于合成的有用的结构单元 生物活性化合物，如K-13，这是一种抑制剂， 血管紧张素转换酶（ACE）。 (d)进一步开发化学芳烃-FeCp阳离子（Cp= eta 5- 以允许芳族化合物的选择性官能化， 配体。 这种化学最具挑战性的方面是 用于转化环己二烯基-FeCp络合物的方法，即 通过亲核试剂加成到芳烃配体、环己烯酮和 相关分子;解决这一未解决问题的研究将是 进行。

The broad, long-term aims of this proposal are to develop applications of arene-metal pi complexes to the total synthesis of challenging molecular arrays that are components of important natural product molecules, and to develop new methodology for asymmetric synthesis based on chiral auxiliary-directed nucleophile additions to arene-metal complexes. The specific aims are listed as follows: (a) Continue investigations directed toward the applications of arene- Mn(CO)3 and arene-RuCp cations in the total synthesis of ristocetin A, a complex glycopeptide that is related to vancomycin and teicoplanin, the molecular structures of which present a challenging opportunity for the development of new and unique methodology for the construction of diary ethers having sensitive attached amino acid and peptide functionality. The glycopeptide targets are of considerable significance and are used as antibiotic active against gram positive bacteria. (b) Explore the applications of arene-metal complexes in the synthesis of enantiomerically pure 4,5-disubstituted cyclohexenones and related compounds, by means of chiral auxiliary-directed asymmetric nucleophile additions to the arene ligand. (c) Initiate studies on ruthenium-promoted intramolecular diary ether formation, and ruthenium-catalyzed diary ether formation, based on observations on the stoichiometric reactions of chloroarene-RuCp cations, which allow direct coupling of protected chloroarylamino acids with protected hydroxyarylamino acids and derived peptides. These methods allow the facile construction of useful building blocks for the synthesis of biologically active compounds such as K-13, which is an inhibitor of angiotensin converting enzyme (ACE). (d) Further develop the chemistry arene-FeCp cations (Cp=eta5- cyclopentadienyl) to allow selective functionalization of the aromatic ligand. The most challenging aspect of this chemistry is the development of methods for the conversion of cyclohexadienyl-FeCp complexes, that are formed by nucleophile addition to the arene ligand, to cyclohexenones and related molecules; studies to address this unsolved problem will be undertaken.