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

描述（由申请人提供）：提出了几种由亲电金络合物催化的新反应。一个主要的重点放在发展的对映选择性C-C和C-X键的结构。一般来说，这些反应涉及？键作为亲电体，在某些情况下通过与阳离子金（I）络合物配位来活化亲核体。一系列的对映选择性转化过程中通过炔或联烯活化将进行研究。研究了手性膦金配合物和手性阴离子催化的对映体选择性反应。这些反应包括通过炔引发的环化级联或通过将碳亲核试剂加成到联烯上形成对映选择性C-C键。后者将应用于呋地洛尔生物碱的合成。亲核试剂的对映选择性分子间加成，或者直接加成到活化的？键或阳离子中间体。本研究将探讨从炔原位生成金（I）-类卡宾中间体的方法及其在对映选择性环加成反应中的应用。此外，金（I）催化的对映选择性反应，通过活化的炔亲核试剂进行将被调查。两者合计，所提出的反应包括亲电体和亲核体活化，并提供对映体选择性进入广泛的碳和杂环结构。还提出了金催化烯烃的反应。这些转化包括金催化的亲核试剂与烯烃的直接加成和金催化的烯烃氧化双官能化。在前者中，将考察由手性金络合物或由质子物种（醇）与手性金络合物配位产生的布朗斯台德酸催化的分子内和分子间对映选择性加成反应。此外，金催化烯烃的氧化官能化，由金诱导的亲核加成引发的？-债券，将开发。这类反应包括涉及亲核试剂与烯烃的分子内和分子间加成的转化，以及所得金中间体与亲核试剂（如硼酸）的分子内和分子间反应。 公共卫生相关性：拟议的计划旨在开发新的方法，用于制备对药物化学具有潜在重要性的结构和化合物。为此，金催化的方法，包括烯选择性反应，用于合成杂环和碳环结构的建议。

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.