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.

描述：（申请人提供）本申请的基本目标是开发和应用新发明的基于硅的 碳碳键形成反应。该程序分为三个 部分：第一和主要的努力将是对 新过程，第二个将是对机制和起源的调查 激活，第三个将是对反应的应用 所选目标的综合，以说明技术的力量。 方法学计划是最广泛的，并细分为许多 项目。首先涉及探索的一般特征 反应，例如硅取代基的性质，观众基团， 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 与新的反应化学。 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场景 硅交叉耦合过程可以起作用，例如：环丙基 - 羟基，烷基，芳基，杂芳基和最重要的是烷烯基烷醇。 这些冒险中的许多将需要开发新方法 引入硅功能。本节中包括 检查有机亲电成分的范围，该范围将作为 交叉偶联反应中的伴侣，例如氯化物，三叶酸盐和 磷酸盐。 机械研究部分将着重于建立速率 方程，配体在钯催化剂中的作用，尤其是在 外部激活器激活硅单元的起源。我们的重点 将在临界跨金属步骤中识别分子细节。 要解决的合成目标属于各种天然产品 家庭。由于本文正在开发的碳碳形成反应是 对于许多结构类型来说，广泛普遍的综合挑战选择 主要是由方法学部分所取得的成功驱动的。 白三烯A4的合成方法是四烯sidechain的青； 详细介绍了吲哚生物碱和C-芳基糖苷papalucandin d。