Cross-Coupling Reactions of Organosilanols

有机硅烷醇的交叉偶联反应

• 批准号: 7578911
• 负责人: Scott Eric Denmark
• 金额: $ 27.26万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7578911
• 关键词: Acids; Address; Antibiotics; Antiviral Agents; Biological; Biological Factors; Carbon; Carbonates; Catalysis; Chloride Ion; Chlorides; Copper; Coupling; Denmark; Development; Epoxy Compounds; Evaluation; Family; Goals; Gold; Hepatitis C; Indole Alkaloids; Intercept; Investigation; Kinetics; Left; Ligands; Mercury; Metals; Methodological Studies; Methods; Nature; Palladium; Polyenes; Process; Reaction; Research Personnel; Role; Scheme; Silanes; Silicon; Structure; Surveys; Technology; Viral; base; diene; oximidine II; programs; silane; silanol; success

The basic objectives of this application are the development and application of a newly invented silicon- based carbon-carbon bond forming reaction that proceeds via a silyloxmetallic intermediate. This programis divided into three sections: the first and major effort will be methodological exploration of the new process, the second will be the investigation of the mechanism, and the third will be the application of the reaction to the synthesis of selected targets that illustrate the power of the technology. The methodological program is the most extensive and is subdivided into many projects. The first involves the development of new and general methods for the introduction of the silanol (or its surrogate) into organic structures using direct installation, cross- and ring closing metathesis and other ring forming processes. The second and most ambitious part of the methodological study is the exploration and development of the various structural scenarios in which the silicon cross coupling process can function, for example: cyclopropyl-, oxiranyl-, aliyl-, alkenyi- aryl-, heteroaryl-, and bifunctional bissiyl dienes. Included in this section will be the examination of the scope of organic electro-philic components that will serve as partners in the cross-coupling reaction such as chlorides and triflates. The extension of the silyloxmetallic intermediate to transmetalation to other metals such as mercury copper and gold will be investigated. The opportunities for catalysis of the transmetalation from silicon to palladium will be studies. The parallels between mercury and gold offer excellent opportunity to use silanols to generate rare organogold(lll) compounds which can be intercepted by conjugate acceptors. The section on mechanistic studies will focus on structurally and kinetically characterizing the silyloxy- metaltic intermediates. A key focus will be to identify the elementary steps in the transmetalation. A major effort will be the development of functionalized ligands to effect nucleopnilic catalysis of transmetalation. The synthesis targets to be tackled belong to a wide range of natural product families. The selection of synthetic challenges is mostly driven by the successes achieved in the methodological section. Synthetic approaches to isodomoic acid H, hepatitis C viral inihibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed.

该应用的基本目标是开发和应用新发明的硅 基于碳-碳键形成反应，通过硅氧金属中间体进行。这个程序是 分为三个部分：第一个也是主要的努力将是新流程的方法论探索， 第二个是机理的研究，第三个是反应的应用 展示该技术力量的选定目标的综合。 该方法计划是最广泛的，并细分为许多项目。第一个 涉及开发将硅烷醇（或其替代物）引入到 使用直接安装、交叉和闭环复分解以及其他成环方式的有机结构 流程。方法论研究的第二个也是最雄心勃勃的部分是探索和 开发硅交叉耦合过程可以发挥作用的各种结构场景， 例如：环丙基-、环氧乙烷基-、烯基-、芳基-、杂芳基-和双官能双硅烷基二烯。包含在 本节将审查有机亲电成分的范围，这些成分将作为 交叉偶联反应中的伙伴，例如氯化物和三氟甲磺酸酯。 将硅氧金属中间体扩展到金属转移到其他金属（例如汞） 铜和金将被调查。从硅到金属转移的催化机会 钯金将被研究。汞和金之间的相似之处为使用硅烷醇提供了绝佳的机会 生成可被共轭受体拦截的稀有有机金（III）化合物。 机理研究部分将重点关注硅氧基的结构和动力学特征。 金属中间体。重点是确定金属转移的基本步骤。一个专业 努力将是开发功能化配体以实现金属转移的核仁催化。 要解决的合成目标属于广泛的天然产物家族。的选择 综合挑战主要是由方法论部分取得的成功推动的。合成的 异冬酰胺酸 H、抑制丙型肝炎病毒的吲哚生物碱、水杨卤酰亚胺的方法 详细介绍了大环内酯肟II和多烯抗病毒抗生素viridemycin。