Microscopy Reveals: Impact of Lithium Salts on Elementary Steps Predicts Organozinc Reagent Synthesis and Structure
Microscopy Reveals: Impact of Lithium Salts on Elementary Steps Predicts Organozinc Reagent Synthesis and Structure
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DOI：
10.1021/jacs.9b02639
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发表时间：
2019-06-26
影响因子：
15
通讯作者：
Blum, Suzanne A.
中科院分区：
文献类型：
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作者：
Jess, Kristof;Kitagawa, Kazuhiro;Blum, Suzanne A.
在有机锌试剂的实际合成中，氯化锂可以促进金属锌粉直接插入到有机卤化物中，但对其特殊能力的原因知之甚少。开创了一个单一的金属颗粒荧光显微镜与H-1 NMR光谱相结合的方法，我们在这里表明，不同的锂盐对增溶中间体的锌金属表面上的有效性建立了一个以前未知的反应性相关性，预测盐的倾向，以促进宏观试剂的合成，并预测最终的有机锌试剂的溶液结构。还鉴定了无盐途径。有机金属表面中间体，其基本步骤的反应性，以及各种合成条件（盐，无盐，温度，搅拌和时间）对其持久性的影响，这些观察是唯一可从显微镜技术的灵敏度和空间定位能力。这些研究在一个统一的机制框架下统一了以前不同的观察结果。该框架能够合理预测盐对有机锌试剂合成和反应性中多个步骤的影响。这是一个早期的例子，单粒子显微镜表征的基本步骤提供预测能力的反应发展，通过获得一个敏感的和选择性的光谱处理的重要中间体，突出了下一代分析工具的作用，在合成化学的发展。
Lithium chloride is known to promote the direct insertion of metallic zinc powder into organohalides in the practical synthesis of organozinc reagents, but the reason for its special ability is poorly understood. Pioneering a combined approach of single-metal-particle fluorescence microscopy with H-1 NMR spectroscopy, we herein show that the effectiveness of different lithium salts toward solubilizing intermediates on the surface of zinc metal establishes a previously unknown reactivity correlation that predicts the propensity of that salt to promote macroscale reagent synthesis and also predicts the solution structure of the ultimate organozinc reagent. A salt-free pathway is also identified. These observations of an organometallic surface intermediate, its elementary-step reactivity, and the impact of various synthetic conditions (salt, salt-free, temperature, stirring, and time) on its persistence, are uniquely available from the sensitivity and spatial localization ability of the microscopy technique. These studies unify previously disparate observations under a single unified mechanistic framework. This framework enables the rational prediction of salt effects on multiple steps in organozinc reagent synthesis and reactivity. This is an early example of single-particle microscopy characterization of elementary steps providing predictive power in reaction development by gaining a sensitive and selective spectral handle on an important intermediate, highlighting the role of this next generation of analytical tools in the development of synthetic chemistry.