Cross-Coupling Reactions of Organosilanols

本申请的基本目标是开发和应用新发明的硅- 通过甲硅烷基氧基金属中间体进行的基于碳-碳键形成反应。该方案是 分为三个部分：第一个也是主要的努力将是对新进程进行方法上的探索， 第二个将是调查的机制，第三个将是应用的反应， 选定目标的合成，说明了技术的力量。 方法学计划是最广泛的，并细分为许多项目。第一 涉及开发新的和通用的方法，用于将硅烷醇（或其替代物）引入 使用直接安装、交叉和环闭合复分解和其他环形成的有机结构 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方案， 实例：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。列入 本节将对有机亲电组分的范围进行审查，这些组分将用作 交叉偶联反应中的伙伴，如氯化物和三氟甲磺酸酯。 将甲硅烷基氧基金属中间体扩展到金属转移到其他金属，如汞 铜和金将被调查。从硅到金属的转移催化的机会， 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 以产生可被共轭受体拦截的稀有有机金（III）化合物。 关于机理研究的部分将集中在结构和动力学表征甲硅烷氧基- 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 将努力开发官能化配体以实现金属转移的亲核催化。 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部分取得的成功推动的。合成 异软骨藻酸H，丙型肝炎病毒抑制吲哚生物碱，水杨酰亚胺 大环内酯肟亚胺II和多烯抗病毒抗生素绿霉素。

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.