Organosilicon-Based Cross-Coupling Reactions

描述：(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硅基 碳-碳键形成反应。这个节目分为三个部分 章节：第一个也是主要的努力将是对 新的过程，第二个将是机制和起源的调查 第三个是将反应应用于 合成选定的目标，说明该技术的威力。方法论方案是最广泛的，并细分为许多 项目。第一个涉及到探索的一般特征的 反应，例如硅取代基的性质，旁观者基团， 催化剂和添加剂。一个重要的子目标是发展 不需要添加氟化物激活剂的程序。接下来， 将开发将硅安装到各种有机骨架中的能力 有了新的反应化学。 方法论研究的第二个也是最雄心勃勃的部分是 探索和开发各种结构方案，在这些方案中 硅交叉偶联工艺可以起作用，例如：环丙基-， 氧杂环丙烷基、炔基、芳基、杂芳基，最重要的是烯基硅烷醇。 其中许多企业将需要开发新的方法来 介绍硅片的功能。此部分将包括 审查将用作以下用途的有机亲电组件的范围 交叉偶联反应中的合作伙伴，如氯化物、三氟化钠和 磷酸盐。 机械研究部分将集中于确定费率。 方程式，配位体在钯催化剂上的作用，特别是在 由外部激活剂激活硅单元的来源。我们的重点是 将是在关键的转金属步骤中确定分子细节。 要攻关的合成目标属于广泛的天然产物 家人。由于这里正在开发的碳-碳形成反应是 广泛适用于多种结构类型，对合成的选择提出了挑战 主要是由方法论部分取得的成功推动的。 白三烯A4四烯侧链的合成方法 详细介绍了吲哚生物碱和C-芳基糖苷类化合物木犀草素D。

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. This program is 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 origin of activation, 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 exploration of the general features of the reaction such as the nature of the silicon substituents, the spectator groups, the catalyst, and additives. An important subgoal is the development of procedures that do not require the addition of fluoride activators. Next, the ability to install silicon into various organic skeletons will be developed with new reaction chemistry. 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-, alkynyl-, aryl-, heteroaryl-, and most importantly alkenylsilanols. Many of these ventures will require the development of new methods for introducing the silicon functionality. Included in this section will be the examination of the scope of organic electrophilic components that will serve as partners in the cross-coupling reaction such as chlorides, triflates and phosphates. The section on mechanistic studies will focus on establishing the rate equation, the role of ligands on the palladium catalyst and particularly on the origin of activation of the silicon unit by the external activators. Our focus will be to identify the molecular detail at the critical transmetalation step. The synthesis targets to be tackled belong to a wide range of natural product families. Since the carbon-carbon forming reaction under development herein is widely general for many structural types, the selection of synthetic challenges is mostly driven by the successes achieved in the methodological section. Synthetic approaches to leukotriene A4 the calyculin A tetraene sidechain, indole alkaloids and the C-arylglycoside papalucandin D are detailed.