Modifying Catalytic Sustainability in Renaud Catalysts: Hints From Aromaticity, Conceptual DFT, and Steric Mapping

Catalytic hydrogenation is a key transformation in the chemical and pharmaceutical industries, traditionally relying on noble‐metal catalysts such as palladium, ruthenium, and iridium. However, the scarcity, high cost, and environmental concerns associated with these metals have motivated the search for sustainable alternatives based on abundant first‐row transition metals. Among them, Knölker‐type iron complexes have emerged as promising candidates for efficient hydrogenation catalysis. This predictive study investigates how structural modifications of the cyclopentadienone ligand of the Renaud ligand and annulated‐ring framework affect the catalytic activity of iron‐based hydrogenation catalysts. Particular attention is devoted to the catalyst activation process and the rate‐determining hydrogenation step. Catalyst activation occurs through CO ligand dissociation promoted by trimethylamine‐N‐oxide, generating the active iron species. The hydrogenation step, involving molecular hydrogen transfer, represents the highest energetic barrier in the catalytic cycle, although protic solvents such as ethanol or water can facilitate this process. The computational results demonstrate that appropriate substituent and ring modifications substantially lower the activation barriers, leading to improved catalytic efficiency. Parameterization by different techniques was performed to understand reactivity trends and interaction patterns.