Cross-Coupling Reactions of Organosilanols

描述（由申请人提供）：本申请的基本目的是开发和应用新发明的硅基碳-碳键形成反应，该反应通过甲硅烷基氧基金属中间体进行。该计划分为3个部分：第一和主要工作将是新工艺的方法学探索，第二将是机制的调查，第三将是反应的应用，以说明技术的力量的选定目标的合成。方法学计划是最广泛的，并细分为许多项目。第一个涉及开发新的和通用的方法，用于使用直接安装，交叉和闭环复分解和其他成环过程将硅烷醇（或其替代物）引入有机结构中。方法学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偶联过程可以发挥作用的各种结构方案，例如：环丙基-，环氧乙烷基-，烯丙基-，烯基-芳基-，杂芳基-和双官能双甲硅烷基二烯。本节将包括检查在交叉偶联反应中作为伙伴的有机亲电组分的范围，如氯化物和三氟甲磺酸酯。将研究甲硅烷氧基金属中间体向汞、铜和金等其他金属的金属转移的延伸。将研究从硅到钯的金属转移催化的机会。汞和金之间的相似之处提供了极好的机会，使用硅烷醇产生罕见的有机金（III）化合物，可以被共轭受体拦截。关于机理研究的部分将集中在结构和动力学表征的硅烷氧基-金属中间体。一个关键的重点将是确定在transmetalation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移。要解决的合成目标属于广泛的天然产物家族。综合挑战的选择主要是由方法部分取得的成功驱动的。详细介绍了异软骨藻酸H、抑制丙型肝炎病毒的吲哚生物碱、水杨酰卤酰亚胺大环内酯肟亚胺II和多烯抗病毒抗生素绿霉素的合成方法。

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.