Screening of the Suzuki Cross-Coupling Reaction Using Desorption Electrospray Ionization in High-Throughput and in Leidenfrost Droplet Experiments
Screening of the Suzuki Cross-Coupling Reaction Using Desorption Electrospray Ionization in High-Throughput and in Leidenfrost Droplet Experiments
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DOI：
10.1007/s13361-019-02287-3
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发表时间：
2019-10-01
影响因子：
3.2
通讯作者：
Cooks, R. Graham
中科院分区：
文献类型：
--
作者：
Fedick, Patrick W.;Iyer, Kiran;Cooks, R. Graham
铃木交叉偶联是一种广泛进行的反应，通常在加热条件下使用金属催化剂。铃木交叉偶联反应的加速以前已经用解吸电喷雾电离质谱仪(DESI-MS)在微滴中进行了探索。在以前工作的基础上，这里介绍了使用高通量Desi-MS筛选系统来确定最佳反应条件。使用自动化系统以接近每小时10,000个反应混合物系统的速度对多种试剂、碱和化学计量进行筛选。DESI-MS系统利用微滴中的反应加速来实现快速筛选。使用该技术筛选一系列反应混合物的结果通过标准的MS成像软件以产品离子图像的形式呈现，便于快速读出。与另一种产生反应加速液滴的方法--莱登弗罗斯特技术--进行了有益的比较。溴化底物的加速因子被测量到大于200，与DESI-MS的结果平行。由于空间效应，加速因子下降到与高度取代的吡啶接近1。反应在莱登弗罗斯特液滴中没有碱的情况下进行，尽管在整体或在DESI-MS筛选实验中没有看到没有碱的产物形成。莱登弗罗斯特化学与高通量DESI中形成的整体和液滴之间的这些差异暂定归因于与莱登弗罗斯特液滴表面相关的极端pH。
Suzuki cross-coupling is a widely performed reaction, typically using metal catalysts under heated conditions. Acceleration of the Suzuki cross-coupling reaction has been previously explored in microdroplets using desorption electrospray ionization mass spectrometry (DESI-MS). Building upon previous work, presented here is the use of a high-throughput DESI-MS screening system to identify optimal reaction conditions. Multiple reagents, bases, and stoichiometries were screened using the automated system at rates that approach 10,000 reaction mixture systems per hour. The DESI-MS system utilizes reaction acceleration in microdroplets to allow rapid screening. The results of screening of an array of reaction mixtures using this technique are presented as product ion images via standard MS imaging software, facilitating quick readout. Instructive comparisons are provided with another method of generating droplets for reaction acceleration-the Leidenfrost technique. Acceleration factors greater than 200 were measured for brominated substrates, paralleling the DESI-MS results. Acceleration factors dropped to near unity with highly substituted pyridines, attributable to a steric effect. The reaction proceeded in the absence of a base in Leidenfrost droplets although no product formation was seen without base in the bulk or in the DESI-MS screening experiments. These differences between Leidenfrost chemistry and the bulk and in droplets formed in high-throughput DESI are tentatively attributed to extremes of pH associated with the surfaces of Leidenfrost droplets.