Catalytic Methods for Carbon-Carbon Bond Formation

碳-碳键形成的催化方法

• 批准号: 6902064
• 负责人: F. Dean Toste
• 金额: $ 24.19万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6902064
• 关键词: alkaloids; alkynes; biological products; carbon; catalyst; chemical bond; chemical synthesis; cyclization; gold; molecular rearrangement; palladium; sesquiterpenes; silver; stereochemistry

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。通常，这些反应涉及通过与阳离子金（I）络合物配位来活化炔或联烯。单体金（I）配合物和金（I）簇用作催化剂，并且显示出不同的反应活性。 金（I）催化β-二羰基化合物与炔和联烯的分子内加成。可采用对炔的加成来产生外-亚甲基环戊烷或-己烷或通过5-内-二取代碳环化来制备环戊烯。还提出了使用其它烯醇化物等价物，例如甲硅烷基烯醇醚和烯胺。这些反应的催化对映选择性版本，使用双钯-银催化剂系统，也将被检查。此外，使用简单烯烃作为金（I）-炔络合物的分子内亲核试剂导致1，5-烯炔异构化为双环[3.1.0]己烯。反应基序也可以与扩环结合使用，以快速生成复杂的碳环框架。 还介绍了一系列重排反应催化剂体系的发展。例如，一个温和的催化Saucy-Marbet重排详细。应用这种重排反应合成了对映体富集的联烯基硅烷和锡烷。该反应被认为是通过金（I）与炔的配位进行的。这种激活模式的应用，其他sigmatropic重排，如科普和奥弗曼重排，也提出了。此外，金（I）催化Nazarov类环化的乙烯基联烯和炔丙醇的频哪醇重排进行了描述。 该提案的一个关键组成部分将是应用新的反应方法来构建复杂的天然产物。靶向两类生物活性天然产物：（I）石松生物碱（II），通过西博尔定A合成说明;（II）和pinguisane倍半萜，通过bisacutifolone A说明。这一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。