Mechanism of iron-catalyzed cross-coupling reactions

铁催化交叉偶联反应的机理

• 批准号: 387444772
• 负责人: Professor Dr. Konrad Koszinowski
• 金额: --
• 依托单位: Institut für Organische und Biomolekulare Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/387444772?language=en
• 关键词: Mechanism; iron; catalyzed; cross; coupling

Transition-metal mediated cross-coupling reactions are of outstanding importance for modern organic synthesis. Thanks to their versatility and efficiency, palladium-catalyzed cross-coupling reactions are particularly popular and have been extensively investigated mechanistically. Nevertheless, they suffer from the high price of palladium, the necessity to use complex and, thus, often expensive ligands, and the toxicity of palladium. A promising alternative relies on cheap and non-toxic iron catalysts for the cross-coupling of Grignard reagents RMgX and other organometallics with alkyl or aryl halides RʹX. However, the poor and insufficient mechanistic understanding of these reactions severely hampers their rational optimization. This project seeks to solve this problem by using a combination of electrospray-ionization (ESI) mass spectrometry, Mößbauer spectroscopy, and gas-phase experiments. As we have demonstrated in the first funding period, ESI mass spectrometry and Mößbauer spectroscopy permit the in-situ analysis of a wide range of intermediates of iron-catalyzed cross-coupling reactions. ESI mass spectrometry is particularly well suited for this purpose because anionic ate species play a central role in iron-catalyzed cross-coupling reactions. Moreover, we have coupled this method with gas-phase experiments for probing the microscopic reactivity of mass-selected organoferrate anions. In this way, we could directly observe individual elementary steps of the catalytic cycle. In the second funding period, we aim at continuing and systematically extending our studies. First, we will consider not only Grignard reagents, but also organolithium, -zinc, and boron compounds as transmetalating agents and examine the effect of alkenes, alkynes, and arenes for stabilizing low-valent organoiron intermediates. Next, we will investigate the kinetics of the reactions of the in-situ formed organoiron species with RʹX substrates. Finally, we will turn to the mass-selected organoferrates in the gas phase. Besides determining their structure by ion-mobility spectrometry, we will analyze their microscopic reactivity in a quantitative manner. For the interpretation of the results from the gas-phase experiments, we will also make use of quantum chemical calculations. Thus, this project promises to make decisive progress in the mechanistic elucidation of iron-catalyzed cross-coupling reactions. In the long term, the obtained mechanistic insight will also contribute to improved practical applications.

过渡金属介导的交叉偶联反应在现代有机合成中具有重要意义。由于其多功能性和效率，钯催化的交叉偶联反应特别受欢迎，并已被广泛研究的机制。然而，它们受到钯的高价格、必须使用复杂的且因此通常昂贵的配体以及钯的毒性的影响。一个有前途的替代方案依赖于廉价和无毒的铁催化剂，用于格氏试剂RMgX和其他有机金属与烷基或芳基卤化物R X的交叉偶联。然而，对这些反应的机理认识不足，严重阻碍了它们的合理优化。该项目试图通过使用电喷雾电离（ESI）质谱，穆斯堡尔谱和气相实验的组合来解决这个问题。正如我们在第一个资助期所展示的那样，ESI质谱和穆斯堡尔谱允许对铁催化交叉偶联反应的各种中间体进行原位分析。ESI质谱法特别适合于此目的，因为阴离子酸盐物质在铁催化的交叉偶联反应中起着核心作用。此外，我们已经将这种方法与气相实验结合起来，用于探测质量选择的有机铁酸盐阴离子的微观反应性。通过这种方式，我们可以直接观察催化循环的各个基本步骤。在第二个资助期内，我们的目标是继续和有系统地扩展我们的研究。首先，我们将考虑不仅格氏试剂，但也有机锂，锌，和硼化合物transmetalating剂和烯烃，炔，芳烃稳定低价有机铁中间体的影响进行检查。接下来，我们将研究原位形成的有机铁物种与R X底物的反应动力学。最后，我们将转向气相中的质量选择性有机铁酸盐。除了通过离子迁移谱确定它们的结构外，我们还将以定量的方式分析它们的微观反应性。为了解释气相实验的结果，我们还将利用量子化学计算。因此，该项目有望在铁催化交叉偶联反应的机理阐明方面取得决定性进展。从长远来看，所获得的机械见解也将有助于改进实际应用。