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）：提出了几种新黄金（I）催化的碳碳格式反应。通常，这些反应涉及通过与阳离子黄金（I）配合物的协调来激活炔烃或艾伦。单体黄金（I）复合物和黄金（I）簇都被用作催化剂，并显示出不同的反应性。 黄金（i）催化分子内添加β-二碳纤维化合物对炔烃和艾伦斯的化合物。可以使用炔烃的添加来产生外乙二烯环戊烷或-HEXANES，或通过5-二进制碳纤维细胞化来制备环戊烯。还提出了使用其他等效物的使用，例如Silyl Enol ethers和Enamines。还将检查这些反应的催化对映选择性版本，使用双钯 - 基形催化剂系统。此外，将简单的烯烃用作分子内亲核试剂朝着黄金（I） - 阿尔基因络合物导致1,5-Enynes到Bicyclo [3.1.0]己an的异构化。反应基序也可以与环膨胀一起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系统的开发。例如，详细介绍了轻度的催化性糖浆粘液重排。提出了将这种重排的应用与映射的甲烷基硅烷硅烷和stannanes合成。据信这种反应是通过将黄金（i）与炔烃协调进行的。还提出了将这种激活方式应用于其他sigmatropic重排，例如COPE和OVERMAN重排。此外，描述了乙烯基艾伦斯的纳扎罗夫样环化的黄金（i）催化的纳扎罗夫样环化和propgylicholic醇的皮奈醇重排。 该提案的一个关键组成部分是将新反应方法应用于复杂天然产品的构建。两类的生物活性天然产物是针对的：（i）由西伯丁a综合说明的番茄生物碱（II）； （ii）和由Bisacutifolone A进行的曲氨酸倍烯烯。该提案整合了方法开发和总合成，以推动有机合成领域及其在生物活性分子制备中的应用。