Cross-Coupling Reactions of Organosilanols

描述（由申请人提供）：本申请的基本目标是开发和应用一种新发明的基于硅的碳-碳键形成反应，该反应通过硅氧金属中间体进行。该计划分为3个部分：第一个也是主要的努力将是对新工艺的方法探索，第二个将是对机制的研究，第三个将是对选定目标的合成反应的应用，以说明该技术的力量。方法论程序是最广泛的，并被细分为许多项目。第一个涉及发展新的和通用的方法来引入硅烷醇（或其替代品）到有机结构中，使用直接安装，交叉和闭合环复合和其他环形成过程。方法研究的第二个也是最雄心勃勃的部分是探索和发展硅交叉偶联过程可以发挥作用的各种结构方案，例如：环丙基-，氧基-，丙基-，烯基-芳基-，杂芳基-和双功能双硅基二烯。本节将包括在交叉偶联反应中作为伙伴的有机亲电成分的范围的检查，如氯化物和三氟酸盐。将研究将硅氧金属中间体扩展到其他金属，如汞、铜和金的金属转化。研究了催化硅金属转化为钯的可能性。汞和金之间的相似之处为利用硅烷醇生成罕见的有机金（ll）化合物提供了极好的机会，这些化合物可以被偶联受体截获。机理研究部分将着重于硅氧基金属中间体的结构和动力学特征。重点将是确定转换中的基本步骤。一个主要的努力将是功能化配体的发展，以实现亲核催化的金属转化。要处理的合成目标属于广泛的天然产物族。综合挑战的选择主要是由方法论部分取得的成功驱动的。详细介绍了异藻酸H、抑制丙型肝炎病毒吲哚类生物碱、水杨酸酰亚胺大内酯肟胺II和多烯抗病毒抗生素病毒霉素的合成方法。

DESCRIPTION (provided by applicant): 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 program is divided into 3 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 studied. 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- metallic 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 nucleophilic 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 inhibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed.