Enantioselective C–H Activations via Cobalt-/Nickel- Electrocatalysis and Iron-Catalyzed C–H Alkylations
by Philipp Boos
Date of Examination:2025-10-28
Date of issue:2025-11-12
Advisor:Prof. Dr. Lutz Ackermann
Referee:Prof. Dr. Lutz Ackermann
Referee:Prof. Dr. Konrad Koszinowski
Referee:Dr. Daniel Janßen-Müller
Persistent Address:
http://dx.doi.org/10.53846/goediss-11604
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Abstract
English
During the past decade, catalytic C–H activation strategies with transition metal catalysts have been established. However, achieving more sustainable enantioselective transformations with cost-effective base metal catalysts remained challenging. To address this limitation, in this thesis, novel enantioselective C–H activation strategies based on cobalt, nickel, and iron catalysis were developed. Moreover, in the devised cobalt- and nickel catalytic systems, electrochemistry could be utilized as an abundant oxidant surrogate to allow efficient catalysis. In addition, the sustainable energy carrier molecular hydrogen (H2) was generated as an attractive byproduct. In the first project, an enantioselective cobaltaelectro-catalyzed annulation of aryl hydrazones with olefins was achieved, furnishing valuable, Fsp³-rich indanes 181 (Scheme 4.1). Moreover, the previously unprecedented potential of novel chiral κ²-N,O-oxazoline enols and amide preligands for enantioselective C–H activation could be demonstrated. Based on these findings, novel chiral κ²-N,O-oxazoline urea and thiourea ligands were designed and synthesized. Thereby challenging enantioselective cobaltaelectrocatalyzed C–H annulations furnished indoles 183 with multiple distinct chiral C–N axes (Scheme 4.2).This electrocatalytic approach is exceptionally mild, straightforward to operate, and generates only molecular hydrogen (H2) as the sole stoichiometric byproduct. With these results, the foundations for the utilization of κ²-N,O-oxazoline urea ligands in enantioselective catalysis are set. Based on the presented data, we anticipate that the devised chiral κ²-N,O-oxazoline preligands provide a valuable contribution to the known chiral ligand toolbox and expect their utilization in enantioselective catalysis in the future. Afterwards, enantioselective cobaltaelectro-catalyzed C–H activations beyond traditional C–H/N–H annulations were explored. More specifically, the robustness of a traceless carboacylation of benzamides 33 with bridged 7-oxabenzonorbornadienes 45 was described (Scheme 4.3). Notably, during this transformation, four stereogenic centers were generated simultaneously. In contrast, nickelaelectro-catalysis was found to be also viable, but furnished the corresponding dihydroisoquinolinones 262. In this case, a data-driven approach guided the discovery of previously unknown chiral Salox ligand derivatives which was essential to achieve high enantioselectivity during catalysis. Moreover, the devised strategy represents the first example of an enantioselective nickelaelectro-catalyzed C–H activation. In the last part of this thesis, the versatility, robustness and product diversification of the first atropo-enantioselective iron-catalyzed C–H alkylation of indoles 187 was showcased (Scheme 4.4). Here, the presence of the chiral NHC ligand L42 with the dispersion energy donor (DED) motifs was essential to achieve high reactivity and selectivity. Noteworthily, during catalysis, C–N axial as well as C-central chirality was successfully induced simultaneously. The desired C(2)-alkylated indole products 188 could be obtained in excellent yields, diastereo- and enantioselectivities.
Keywords: Organic Chemistry; Catalysis; Electrochemistry
