Catalytic Methods for Carbon-Carbon Bond Formation

碳-碳键形成的催化方法

• 批准号: 7391247
• 负责人: F. Dean Toste
• 金额: $ 24.72万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391247
• 关键词: 1-hexene; Alcohols; Alkenes; Alkynes; Area; Biological Factors; Carbon; Catalysis; Chemicals; Class; Complex; Cyclization; Cyclopentane; Cyclopentenes; DNA Sequence Rearrangement; Development; Ethers; Ethyl Ether; Facility Construction Funding Category; Goals; Gold; Hexanes; Methodology; Methods; Numbers; Object Attachment; Organic Synthesis; Palladium; Preparation; Process; Purpose; Range; Reaction; Research; Sesquiterpenes; Silanes; Silver; Structure; System; Therapeutic Agents; Transition Elements; carbene; catalyst; chemical synthesis; coping; enol; enolate; lycopodium alkaloid; metal complex; method development; novel; programs; propadiene; sieboldine A; silane; tool

DESCRIPTION (provided by applicant): Several new gold(I) catalyzed carbon-carbon formatting reactions are proposed. In general, these reactions involve activation of alkynes or allenes by coordination to cationic gold(I) complexes. Both monomeric gold(I) complexes and gold(I) clusters are employed as catalysts and show distinct reactivities. Gold(I) catalyzes the intramolecular addition of beta-dicarbonyl compounds to alkynes and allenes. Additions to alkynes can be employed to produce either exo-methylene cyclopentanes or -hexanes or to prepare cyclopentenes through a 5-endo-dig carbocyclizations. Use of other enolate equivalents, such as silyl enol ethers and enamines is also proposed. Catalytic enantioselective versions of these reactions, using a dual palladium-silver catalysts system, will also be examined. Additionally, the use of simple olefins as intramolecular nucleophiles towards gold(I)-alkyne complexes results in the isomerization of 1,5-enynes to bicyclo[3.1.0]hexenes. The reaction motif can also be used in conjunction with a ring expansion to rapidly generate complex carbocyclic frameworks. Development of catalyst systems for a range of rearrangement reaction is also described. For example, a mild catalytic Saucy-Marbet rearrangement is detailed. Application of this rearrangement to the synthesis of enantioenriched allenyl silanes and stannanes is proposed. The reaction is believed to proceed by coordination of gold(I) to an alkyne. Application of this mode of activation to other sigmatropic rearrangements, such as the Cope and Overman rearrangements, is also proposed. Additionally, gold(I) catalyzed Nazarov-like cyclization of vinyl allenes and the pinacol rearrangements of propargylic alcohols are described. A key component of this proposal will be the application of new reaction methodology to the construction of complex natural products. Two classes of bioactive natural product are targeted: (I) the lycopodium alkaloids(II), illustrated by a sieboldine A synthesis; (II) and the pinguisane sesquiterpenes, exemplified by bisacutifolone A. This proposal integrates method development and total synthesis to advance the field of organic synthesis and its application to the preparation of bioactive molecules.

描述（由申请人提供）：提出了几种新的金（I）催化的碳-碳格式化反应。一般来说，这些反应涉及通过与阳离子金(I)络合物配位来活化炔烃或丙二烯。单体金（I）配合物和金（I）簇都用作催化剂并表现出不同的反应活性。 金 (I) 催化 β-二羰基化合物与炔烃和丙二烯的分子内加成。与炔烃的加成可用于生产外型亚甲基环戊烷或正己烷，或通过5-内位碳环化制备环戊烯。还建议使用其他烯醇等同物，例如甲硅烷基烯醇醚和烯胺。还将研究使用双钯-银催化剂系统的这些反应的催化对映选择性版本。此外，使用简单烯烃作为金(I)-炔配合物的分子内亲核试剂会导致1,5-烯炔异构化为双环[3.1.0]己烯。该反应基序还可以与环扩展结合使用，以快速生成复杂的碳环框架。 还描述了用于一系列重排反应的催化剂体系的开发。例如，详细描述了温和的催化 Saucy-Marbet 重排。提出了将该重排应用于合成对映体富集的丙二烯基硅烷和锡烷。据信该反应是通过金(I)与炔的配位进行的。还建议将此激活模式应用于其他 sigmatropic 重排，例如 Cope 和 Overman 重排。此外，还描述了金（I）催化的乙烯基丙二烯的类纳扎罗夫环化和炔丙醇的频哪醇重排。 该提案的一个关键组成部分是将新的反应方法应用于复杂天然产物的构建。目标是两类具有生物活性的天然产物：(I) 石松生物碱(II)，以 sieboldine A 合成为例； (II)和pinguisane倍半萜，以bisacutifolone A为例。该提案将方法开发和全合成结合起来，以推进有机合成领域及其在生物活性分子制备中的应用。