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，以实现下一步 合成化学中的机械论研究的产生。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理作用 通过开发灵敏的荧光显微镜，将有机卤化物转化为商业金属粉末 技巧。将有机卤化物直接插入商业金属粉末将是最方便的， 一系列金属有机试剂的原子经济性和潜在成本效益的合成 催化剂，但目前只对几种金属有效(例如，要制造的镁 格氏试剂)。这种直接插入过程的推广长期以来一直受到 大多数商用金属粉末的抗氧化性。特定的溶剂或添加剂，如 盐导致少数最初不活跃的金属变得活跃(例如，铟或锌与氯化锂在 “诺切尔协议”)。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。 这种缺乏知识的原因是很难检测到该领域的少量中间体 机械化化学，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。这两个缺口都被这个方案中的荧光实验所克服 显微镜。中心假设是提供对合成的指导性洞察的新的中间体 有机金属试剂和发展成催化反应可以通过灵敏的发现 使用新型显像剂的荧光显微镜。这种方法是创新的，因为它为 单分子和粒子水平的机械研究，而传统的机械工具是 最适合仅测量混合物中的主要成分。核心假设将通过以下方式进行检验 追求三个具体目标：1)确定盐和溶剂直接影响的机理来源 有机卤化物与商品铝、铟和锌的金属粉末的插入反应及其用途 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 从Rieke锌形成有机锌试剂中的盐类；以及3)识别能够使直接 添加到商用铜和钯粉末中，其中这种添加效应基本上是未知的。 拟议中的实验的影响有两个方面：1)它们将为 直接从商业金属粉末中开发合成有用的反应，以及2)它们将 为合成化学家开发新的机械工具，其灵敏度高达单分子检测。 这些研究将是第一批此类单分子/粒子荧光显微镜研究之一。 有机化学，包括第一个3D超分辨率和双试剂/双色多步机理 在这一领域的研究，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.