Cross-Coupling Reactions of Organosilanols

本申请的基本目标是开发和应用一种新发明的硅- 通过硅氧金属中间体进行的基于碳-碳键的形成反应。这项计划 分为三个部分：第一个也是主要的努力将是对新进程的方法探索， 第二个是反应机理的研究，第三个是反应在反应中的应用 所选目标的合成说明了该技术的威力。 方法论方案是最广泛的，并细分为许多项目。第一 包括开发新的和通用的方法将硅醇(或其替代品)引入 使用直接安装、交叉和环合复化以及其他成环的有机结构 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 开发硅交叉耦合工艺可以发挥作用的各种结构方案， 例如：环丙基、氧杂环丙基、芳基、烯基、杂芳基和双官能双硅双烯。包括在 这一部分将审查有机亲电组件的范围，这些组件将用作 在交叉偶联反应中的伙伴，如氯化物和三氟化物。 硅氧金属中间体向汞等其他金属过渡的延伸 铜和黄金将被调查。从硅到硅的转金属催化机会 钯将被研究。汞和金之间的相似之处为使用硅烷醇提供了极好的机会 以生成可被共轭受体截取的稀有有机金(111)化合物。 力学研究部分将集中在硅氧基的结构和动力学特征上。 金属中间体。一个关键的焦点将是确定转金属过程中的基本步骤。一位少校 努力开发官能化的配体来实现转金属的核苷催化作用。 要攻克的合成目标属于广泛的天然产物家族。评选 综合挑战主要是由方法论部分取得的成功推动的。合成的 异藻酸H、抑制丙型肝炎病毒的吲哚生物碱、水杨酰亚胺的研究进展 详细介绍了大内酯、羟亚胺II和多烯类抗病毒抗生素维维菌素。

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.