Catalytic Methods for Carbon-Carbon and Carbon-Heteroatom Bond Formation

描述(由申请人提供)：提出了几个由亲电金络合物催化的新反应。重点介绍了对映选择性C-C和C-X键结构的发展。一般来说，这些反应包括？-键作为亲电性的活化，在某些情况下，通过与阳离子金(I)络合物的配位而激活亲核性。将研究一系列通过炔烃或烯丙烯活化进行的对映选择性转化。这些研究包括手性膦(I)络合物和/或手性阴离子催化的对映选择性反应。这些反应包括通过炔引发的环化级联反应或通过将碳亲核试剂加到烯上而形成对映体选择性的C-C键。后者将应用于白屈菜素生物碱的合成。还提出了亲核试剂的不对称分子间加成反应，可以直接加成活化的？-键，也可以加成阳离子中间体。本课程将考察由炔烃原位生成金(I)-类卡宾中间体及其在不对称环加成反应中的应用。此外，还将研究金(I)催化的对映选择性反应，这些反应通过烯烃作为亲核试剂的活化而进行。综上所述，建议的反应包括亲电活性和亲核活性，并提供对映体选择性进入广泛的碳环和杂环结构。还提出了金催化的烯烃反应。这些转化包括金催化的亲核剂与烯烃的直接加成反应和金催化的烯烃氧化双官能化反应。在前者中，我们将考察手性金配合物或手性金配合物与质子醇配位生成的Bronsted酸催化的分子内和分子间对映选择性加成反应。此外，由金诱导的亲核加成反应引发的烯烃氧化官能化也将得到发展。这类反应包括亲核剂与烯烃在分子内和分子间加成的转化，以及生成的金中间体与亲核剂(如硼酸)在分子内和分子间的反应。 公共卫生相关性：拟议的计划旨在开发制备对药物化学具有潜在重要性的结构和化合物的新方法。为此，人们提出了金催化合成杂环和碳环结构的方法，包括遗传选择性反应。

DESCRIPTION (provided by applicant): Several new reactions, catalyzed by electrophilic gold complexes, are proposed. A major emphasis is placed on the development of enantioselective C-C and C-X bond constructions. In general, these reactions involve activation of ?-bonds as electrophiles, in some cases activation of nucleophiles, by coordination to cationic gold(I) complexes. A range of enantioselective transformation proceeding via alkyne or allene activation will be investigated. The proposed studies include enantioselective reactions catalyzed by chiral phosphinegold(I) complexes and/or chiral anions. These reactions include enantioselective C-C bond formation through alkyne initiated cyclization cascades or by addition of carbon nucleophiles to allenes. The latter will be applied to the synthesis of the flinderole alkaloids. Enantioselective intermolecular addition of nucleophiles, either directly to the activated ?-bond or to a cationic intermediate, is also proposed. Methods that involve in situ generation of gold(I)-carbenoid intermediates from alkynes and their use in enantioselective cycloaddition reactions will be examined. Additionally, gold(I)-catalyzed enantioselective reactions that proceed through activation of alkynes as nucleophiles will be investigated. Taken together, the proposed reactions encompass both electrophile and nucleophile activation and provide enantioselective entries into a wide range of carbo- and heterocyclic structures. Gold-catalyzed reactions of alkenes are also proposed. These transformations include gold-catalyzed direct addition of nucleophiles to alkenes and gold-catalyzed oxidative difunctionalization of alkenes. In the former, intra- and intermolecular enantioselective addition reactions catalyzed by chiral gold complexes or Bronsted acids generated by coordination of protic species (alcohols) to chiral gold-complexes will be examined. Additionally, gold-catalyzed oxidative functionalization of alkenes, initiated by gold-induced nucleophilic addition to the ?-bond, will be developed. This reaction class includes transformations involving intra- and intermolecular addition of nucleophiles to alkenes and intra- and intermolecular reaction of the resulting gold intermediate with nucleophiles (such as boronic acids). PUBLIC HEALTH RELEVANCE: The proposed program aims to develop new methods for the preparation of structures and compounds of potential importance to medicinal chemistry. To this end, gold-catalyzed methods, including eneatioselective reactions, for synthesis of heterocyclic and carbocyclic structures are proposed.