Catalytic Methods for Carbon-Carbon Bond Formation

碳-碳键形成的催化方法

• 批准号: 7930038
• 负责人: F. Dean Toste
• 金额: $ 18.32万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7930038
• 关键词: 1-hexene; Alcohols; Alkenes; Alkynes; Area; Biological Factors; Carbon; Catalysis; Chemicals; Complex; Cyclization; Cyclopentane; Cyclopentenes; DNA Sequence Rearrangement; Development; Ethers; Goals; Gold; Hexanes; Methodology; Methods; Organic Synthesis; Palladium; Preparation; Process; 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)：提出了几个新的金(I)催化的碳-碳格式化反应。一般说来，这些反应包括通过与阳离子金(I)络合物配位来活化炔烃或烯烃。单体金(I)络合物和金(I)簇合物都被用作催化剂，并表现出明显的反应活性。 金(I)催化β-二羰基化合物与炔烃和联烯的分子内加成反应。对炔烃的加成可用于生产外亚甲基环戊烷或-己烷，或通过5-内挖碳环化反应制备环戊烯。还建议使用其他烯酸酯类化合物，如硅烯醇醚和烯胺。这些反应的催化对映体选择性版本，使用双钯-银催化剂体系，也将被审查。此外，使用简单的烯烃作为分子内亲核试剂对金(I)-烯烃络合物的反应导致1，5-烯炔异构化为双环[3.1.0]己烯。该反应基序还可以与扩环一起使用，以快速生成复杂的碳环骨架。 还介绍了用于一系列重排反应的催化剂体系的发展。例如，温和催化的Saucy-Marbet重排被详细介绍。提出了该重排反应在富含对映体的烯丙基硅烷和锡烷合成中的应用。该反应被认为是通过金(I)配位生成乙炔而进行的。我们还建议将这种激活模式应用于其他的S型重排，如Cope重排和Overman重排。此外，还描述了金(I)催化的乙烯基烯的纳扎罗夫环化反应和丙叉醇的片呐醇重排反应。 这项提议的一个关键组成部分将是将新的反应方法应用于复杂天然产品的构建。我们的目标是两类生物活性天然产物：(I)石松生物碱(II)，以西波尔丁A为例；(Ii)石松烷倍半萜，以双五叶草酮A为例。该建议将方法开发和全合成相结合，以推进有机合成领域及其在生物活性分子制备中的应用。