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

Abstract

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 (EWG) 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 groups on the cyclopentadienone would not lead to the reductive amination but to undesired dimerization. A possible solution consists in the addition of phenyl substituents in the cyclopentadienone 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 approach. We have found that some electron withdrawing groups in the phenyl groups facilitate the reductive amination of imines. This computational result has been later on confirmed experimentally, and therefore, we have computationally designed new catalysts that improve the performance of the previous known Knölker-type iron complexes