Enhancement of Knölker Iron Catalysts for Imine Hydrogenation by Predictive Catalysis: From Calculations to Selective Experiments

• Published in: Organometallics 2023-07, Vol.42 (14), p.1784-1792
• Main Authors: Joly, Nicolas, Gimferrer, Martí, Escayola, Sílvia, Cendra, Maria, Coufourier, Sébastien, Lohier, Jean-François, Gaillard, Quentin Gaignard, Gaillard, Sylvain, Solà, Miquel, Renaud, Jean-Luc, Poater, Albert
• Format: Article
• Language: English
• Subjects: Chemical Sciences
• ISSN: 0276-7333; 1520-6041
• DOI: 10.1021/acs.organomet.3c00025

The reductive amination reaction of imines catalyzed by Knölker-type iron complexes under hydrogen at high pressure is very interesting in synthetic terms. This type of reaction is an important catalytic challenge, since harsh conditions are necessary and do not occur easily. In a previous work ( Organometallics 2022, 41, 1204−1215), we carried out a computational study of the reaction mechanism showing that electron-withdrawing groups (EWGs) attached to the cyclopentadienone of the Knölker-type iron complexes favor the reductive amination of imines. The synthesis of Knölker-type iron complexes with cyclopentadienones having EWGs is not straightforward, since the direct bonding of EWGs on the cyclopentadienone would lead not to the reductive amination but to undesired dimerization. A possible solution consists in the addition of phenyl substituents in the cyclopentadienones of these catalysts and then introduction of EWGs in the phenyl rings. We have performed computational studies using density functional theory (DFT) for the reductive amination of imines to analyze the efficiency of such an approach. We have found that some EWGs in the phenyl groups facilitate the reductive amination of imines. This computational result has been later confirmed experimentally, and therefore, we have computationally designed new catalysts that improve the performances of the previously known Knölker-type iron complexes.