Organosilicon-Based Cross-Coupling Reactions

有机硅交叉偶联反应

• 批准号: 7163202
• 负责人: Scott Eric Denmark
• 金额: $ 9.18万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163202
• 关键词: catalyst; chemical group; chemical synthesis; covalent bond; organometallic compounds; silicon compounds

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.

描述：（申请人提供）本申请的基本目的是开发和应用一种新发明的硅基材料 碳-碳键形成反应。本次计划分为三部分 部分：第一个也是主要的努力将是方法论探索 新流程，第二是机制和起源的调查 活化，第三个是将反应应用到 综合展示该技术力量的选定目标。 该方法计划是最广泛的，并细分为许多 项目。第一个涉及探索一般特征 反应，例如硅取代基的性质、观众群体、 催化剂、添加剂。一个重要的子目标是发展 不需要添加氟化物活化剂的程序。接下来， 将开发将硅安装到各种有机骨架中的能力 具有新的反应化学。 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情景，其中 硅交联过程可以发挥作用，例如：环丙基， 环氧乙烷基、炔基、芳基、杂芳基和最重要的烯基硅烷醇。 其中许多企业将需要开发新方法 介绍硅的功能。本节中将包括 检查有机亲电子成分的范围，这些成分将作为 交叉偶联反应中的伙伴，例如氯化物、三氟甲磺酸酯和 磷酸盐。 机制研究部分将重点关注确定速率 方程，配体在钯催化剂上的作用，特别是在 硅单元被外部活化剂活化的起源。我们的重点 将是确定关键的金属转移步骤的分子细节。 所要解决的合成目标属于广泛的天然产物 家庭。由于本文中开发的碳-碳形成反应是 对于许多结构类型来说广泛通用，合成挑战的选择 主要是由方法论部分取得的成功推动的。 白三烯 A4 花萼素 A 四烯侧链的合成方法， 详细介绍了吲哚生物碱和 C-芳基糖苷巴帕鲁坎定 D。