Low-Valent Cobalt-Catalyzed C-H Activation: Mechanistic Insight for Synthetic Applications

• Applicants: Professor Dr. Lutz Ackermann; Professor Dr. Konrad Koszinowski
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 289205672

The advent of practical transition metal-catalyzed C-H activation reactions is currently revolutionizing organic synthesis. Thanks to their ubiquity in organic molecules, C-H bonds represent ideal targets for a direct functionalization approach. The resulting synthetic routes are short and efficient, thus saving resources and generating less waste. At the same time, C-H functionalizations are inherently challenging due to the low intrinsic reactivity of the C-H bond and the difficulty to control the site-selectivity. Most current methods rely on 4d transition metals as catalysts, whose high prices severely compromise the sustainability of the approach, however. Therefore, practical C-H functionalizations employing naturally abundant 3d transition metals as catalysts are in high demand. Very recent work points to low-valent cobalt complexes as particularly active and promising catalysts. As the molecular mode of action of these catalysts is almost completely unknown, their rational and systematic improvement today is impossible. The present proposal seeks to change this situation. In the first step, it aims at the full mechanistic elucidation of cobalt-catalyzed C-H functionalizations. To this end, it will characterize the in situ-formed reaction intermediates by electrospray-ionization mass spectrometry. This analytical method is particularly well-suited for this purpose because it selectively detects charged species, which supposedly play a crucial role in cobalt-catalyzed C-H functionalizations. Preliminary results fully confirm this notion. Additional experiments will probe the microscopic reactivity of mass-selected cobalt complexes in the gas phase as well as the reaction kinetics in solution. In the second step, the project will build upon the gained mechanistic insight to develop novel methods for cobalt-catalyzed C-H functionalizations. The careful design of ligands shall make possible the functionalization of unactivated C(sp3)-H bonds. Moreover, it will be attempted to replace the currently required Grignard reagents for milder bases, thereby boosting the functional-group tolerance of the reactions. Thus, the newly developed methods will greatly enhance the utility of C-H functionalization reactions for organic synthesis.

• DFG Programme: Research Grants