Mechanism of iron-catalyzed cross-coupling reactions

• Applicant: Professor Dr. Konrad Koszinowski
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Analytical Chemistry ; Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387444772

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.

• DFG Programme: Research Grants