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

Abstract

The reductive amination reaction of imines catalyzed by Knolker-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(Organometallics , 41, 1204(Organometallics −1215, we carried out a computational study of the reaction mechanism showing that electron-withdrawing groups (EWGs) attached to the cyclopentadienone of the Knolker-type iron complexes favor the reductive amination of imines. The synthesis of Knolker-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 Knolker-type iron complexes.

%VBur index and steric maps: from predictive catalysis to machine learning

“…80 However, other became successful, with next experimental studies, take for instance, with regard to the functionalization of carbon allotropes, Poater predicted the reactivity and regioselectivity of the Pauson-Khand reaction in armchair, zig-zag and chiral nanotubes, 81 a reaction that was then carried out in the laboratory in collaboration with Prof. Fernando Langa (UCM); or in collaboration with Prof. Jean-Luc Renaud the successful reductive amination by bifunctional(cyclopentadienone)Iron-Tricarbonyl Complexes, 82 analogous to Kno ¨lker catalysts, moving to mild conditions simply adding electronwithdrawing groups on the cyclopentadienone ring. 63,83 2.4. Hot topics in computational chemistry Some of the hot topics in computational chemistry are the following, in which %V Bur or/and steric maps have or could have a role: (1) Reaction mechanisms: computational methods can be used to study reaction mechanisms and predict reaction pathways, which is useful for developing new synthetic methods and understanding chemical reactivity; (2) Sustainable chemistry: computational chemistry is also being used to develop sustainable chemical processes and materials, such as renewable energy sources and biodegradable plastics;…”

“…Nevertheless, the pivotal aspect remains that calculations are conducted prior to experiments, resulting in reduced experimental needs owing to predictions derived from computations. Examples of Poater's work in predictive chemistry and predictive catalysis include the development of computational tools and methods to predict the properties, 61 reactivity, 62,63 and behaviour of chemical compounds and catalysts. 64 However, the range of uses and applications is much broader, including the development of ML algorithms to predict the reactivity of chemical compounds based on their molecular structure and properties, 64 while there are other examples using computational models to predict the performance of catalysts in chemical reactions, 57 including the rate and selectivity of the reaction.…”

“…80 However, other became successful, with next experimental studies, take for instance, with regard to the functionalization of carbon allotropes, Poater predicted the reactivity and regioselectivity of the Pauson–Khand reaction in armchair, zig-zag and chiral nanotubes, 81 a reaction that was then carried out in the laboratory in collaboration with Prof. Fernando Langa (UCM); or in collaboration with Prof. Jean-Luc Renaud the successful reductive amination by bifunctional(cyclopentadienone)Iron–Tricarbonyl Complexes, 82 analogous to Knölker catalysts, moving to mild conditions simply adding electronwithdrawing groups on the cyclopentadienone ring. 63,83…”

Cyclopentadienone Iron Complex-Catalyzed Hydrogenation of Ketones: The Influence of the Charge-Tag on Catalytic Performance

“…Such effects have been described before by Renaud, Poater, and co-workers, who have found that an increase in electron density in the cyclopentadienone ring leads to increased catalytic performance. 56,57 Furthermore, it was reported that introducing an oxygen atom in the β-position to the cyclopentadienone ring as a five-membered cyclic ether moiety leads to lower yields in reductive amination reactions compared to Fe TMS (CO) 3 , indicative that the presence of an electronegative heteroatom in this position leads to lower catalytic performance. 58 Funk et al have also very recently reported the variation of substituents on the aryl groups in tetraphenylcyclopentadienone-based iron complexes, where they have shown that electron-donating groups lead to higher reaction rates and electron-withdrawing groups lead to lower reaction rates.…”