Fluorescence Microscopy for the Development of Organometallic Reagents and Catalysts from Metal Powders

项目摘要 这项研究计划的长期目标是开发成像方法，以实现下一个 合成化学中的机械研究的产生。此应用程序的总体目标是 确定添加剂和溶剂在实现直接插入反应中的机械作用， 通过发展灵敏的荧光显微镜， 技术.将有机卤化物直接插入到商业金属粉末中将是最方便的， 原子经济的，和潜在的成本有效的合成范围广泛的有机金属试剂和 催化剂，但它目前仅对少数金属起作用（例如，镁制造 Grignard试剂）。这种直接插入过程的推广长期以来一直受到 大多数商业金属粉末对氧化添加的抗性。特定溶剂或添加剂，如 盐使少量最初不反应的金属变得活性（例如，铟或锌与氯化锂， “Knochel协议”）。然而，这些添加剂和溶剂的机械作用在很大程度上是未知的。 这种知识的缺乏是由于难以检测到该领域中的少量中间体。 机械化学，这种缺乏限制了化学计量的直接插入反应的发展。 和催化系统。这两个差距都克服了实验在这个建议与荧光 显微镜中心假设是新的中间体为合成提供了指导性见解 有机金属试剂和催化反应的发展，可以发现通过敏感 荧光显微镜与新的成像剂。这种方法是创新的，因为它开发了工具， 在单分子和粒子水平的机械研究，而传统的机械工具， 最适合仅测量混合物中的主要成分。中心假设将通过以下方式进行检验： 追求三个具体目标：1）确定盐和溶剂对直接反应的作用机理。 有机卤化物与铝、铟和锌的商业金属粉末的插入反应，并使用该方法 扩大从有机氯化物合成有机铟试剂的途径的知识; 2）确定作用 3）确定能够直接从Rieke锌形成有机锌试剂的添加剂 插入到商业铜和钯粉末中，其中这种添加剂效应基本上是未知的。 所提出的实验的影响是双重的：1）它们将提供指导机制信息， 直接从商业金属粉末中开发合成有用的反应，2）它们将 为合成化学家开发灵敏度高达单分子检测的新机械工具。 这些研究将是2010年首次进行的此类单分子/颗粒荧光显微镜研究之一。 有机化学，包括第一个三维超分辨和双试剂/双色多步机理 这一领域的研究，为合成化学界开辟了新的研究领域。

Project Summary The long-term objective of this research program is to develop imaging approaches to enable the next generation of mechanistic studies in synthetic chemistry. The overall objective for this application is to determine the mechanistic roles of additives and solvents in enabling the direct insertion reactions of organohalides to commercial metal powders, through the development of sensitive fluorescence microscopy techniques. The direct insertion of organohalides to commercial metal powders would be the most convenient, atom-economical, and potentially cost effective synthesis for a wide range of organometallic reagents and catalysts across the periodic table, but it currently works for only a few metals (e.g., magnesium to make Grignard reagents). The generalization of this direct insertion process has long been hampered by the resistance of most commercial metal powders toward oxidative addition. Specific solvents or additives such as salts cause a handful of initially unreactive metals to become active (e.g., indium or zinc with lithium chloride in the “Knochel protocol”). The mechanistic roles of these additives and solvents, however, are largely unknown. This lack of knowledge arises from the difficulty in detecting small quantities of intermediates in the field of mechanistic chemistry, and this lack is limiting the development of direct insertion reactions for stoichiometric and catalytic systems. Both of these gaps are overcome by the experiments in this proposal with fluorescence microscopy. The central hypothesis is that new intermediates that provide guiding insight into the synthesis of organometallic reagents and into the development of catalytic reactions can be discovered through sensitive fluorescence microscopy with novel imaging agents. This approach is innovative because it develops tools for mechanistic investigations at the single-molecule and -particle level, whereas traditional mechanistic tools are best suited to measuring only the major components in mixtures. The central hypothesis will be tested by pursuing three specific aims: 1) Determine the mechanistic origin of the salt and solvent effects on the direct insertion reactions of organohalides to commercial metal powders of aluminum, indium, and zinc, and use this knowledge to expand synthetic access to organoindium reagents from organochlorides; 2) Determine the role of salts in the formation of organozinc reagents from Rieke zinc; and 3) Identify additives that enable direct insertion to commercial copper and palladium powders, wherein such additive effects are essentially unknown. The impact of the proposed experiments is two-fold: 1) They will provide guiding mechanistic information for the development of synthetically useful reactions directly from commercial metal powders, and 2) They will develop new mechanistic tools for synthetic chemists with sensitivity as high as single-molecule detection. These studies will be among the first of any such single-molecule/-particle fluorescence microscopy studies in organic chemistry, and include the first 3D-superresolution and two-reagent/two-color multistep mechanistic studies in this field, opening new areas of research for the synthetic chemistry community.