Organosilicon-Based Cross-Coupling Reactions

有机硅交叉偶联反应

• 批准号: 6621200
• 负责人: Scott Eric Denmark
• 金额: $ 27.01万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621200
• 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.

说明：（申请人提供）本申请的基本目的 是新发明的硅基 碳-碳键形成反应。本方案分为三个 第一个也是主要的努力将是对 新的过程中，第二将调查的机制和起源 第三个将是反应的应用， 选定目标的综合，说明了技术的力量。 方法论的程序是最广泛的，并细分为许多 项目第一个涉及的一般特征的探索 反应如硅取代基的性质，旁观者基团， 催化剂和添加剂。一个重要的次级目标是发展 不需要添加氟化物活化剂的方法。接下来 将开发将硅安装到各种有机骨架中的能力 新的化学反应。 方法论研究的第二个也是最雄心勃勃的部分是 勘探和开发的各种结构方案，其中 硅交叉偶联工艺可以起例如：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的方法， 引入硅功能。本节将包括 检查有机亲电组分的范围， 交叉偶联反应中的伙伴，如氯化物，三氟甲磺酸酯和 磷酸盐 关于机制研究的部分将侧重于确定 方程式中，配体对钯催化剂，特别是对 硅单元被外部活化剂活化的起源。我们的重点 将是在关键的金属转移步骤中确定分子细节。 所要解决的合成目标属于广泛的天然产物 家庭由于在此开发的碳-碳形成反应是 广泛适用于许多结构类型，选择合成挑战 主要是由方法部分取得的成功推动的。 白三烯A4的合成方法， 吲哚生物碱和C-芳基糖苷papalucandin D进行了详细说明。