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

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.