Homogeneously catalyzed reactions often make use of additives and promotors that affect reactivity patterns and improve catalytic performance. While the role of reaction promotors is often discussed in view of their chemical reactivity, we demonstrate that they can be involved in catalysis indirectly. In particular, we demonstrate that promotors can adjust the thermodynamics of key transformations in homogeneous hydrogenation catalysis and enable reactions that would be unfavorable otherwise. We identified this phenomenon in a set of well-established and new Mn pincer catalysts that suffer from persistent product inhibition in ester hydrogenation. Although alkoxide base additives do not directly participate in inhibitory transformations, they can affect the equilibrium constants of these processes. Experimentally, we confirm that by varying the base promotor concentration one can control catalyst speciation and inflict substantial changes to the standard free energies of the key steps in the catalytic cycle. Despite the fact that the latter are universally assumed to be constant, we demonstrate that reaction thermodynamics and catalyst state are subject to external control. These results suggest that reaction promotors can be viewed as an integral component of the reaction medium, on its own capable of improving the catalytic performance and reshaping the seemingly rigid thermodynamic landscape of the catalytic transformation.

The choice of a solvent and the reaction conditions often defines the overall behavior of a homogeneous catalytic system by affecting the preferred reaction mechanism and thus the activity and selectivity of the catalytic process. Here, we explore the role of solvation in the mechanism of ketone reduction using a model representative of a bifunctional Mn-diamine catalyst through density functional theory calculations in a microsolvated environment by considering explicit solvent and fully solvated ab initio molecular dynamics simulations for the key elementary steps. Our computational analysis reveals the possibility of a Meerwein-Ponndorf-Verley (MPV) type mechanism in this system, which does not involve the participation of the N-H moiety and the formation of a transition-metal hydride species in ketone conversion. This path was not previously considered for Mn-based metal-ligand cooperative transfer hydrogenation homogeneous catalysis. The MPV mechanism is strongly facilitated by the solvent molecules present in the reaction environment and can potentially contribute to the catalytic performance of other related catalyst systems. Calculations indicate that, despite proceeding effectively in the second coordination sphere of the transition-metal center, the MPV reaction path retains the enantioselectivity preference induced by the presence of the small chiral N,N′-dimethyl-1,2-cyclohexanediamine ligand within the catalytic Mn(I) complex.

Reversible dissociation of H−X bond (M−L+H−X→M(X)-L(H); (Formula presented.)) is an important step during pre-activation, catalysis and possible deactivation of acid-base cooperative pincer based transition metal catalysts (M−L). Herein we carried out a high-throughput computational investigation of the thermodynamic stability of different adducts in various functionalized Mn(I) based pincer complexes. We used a combination of density functional theory (DFT) and density functional tight binding (DFTB) calculations to analyze (Formula presented.) of >700 (M(X)-L(H)) intermediates based on functionalized variants of four pincer type ligand scaffolds derived from PCP, CNC, PNP and SNS ligands. We discovered linear scaling relations between (Formula presented.) of various species. Strongest correlations were found between species of similar size and chemical nature e. g. (Formula presented.) correlated best with (Formula presented.) and worst with (Formula presented.). Such scaling relations can be useful for property based screening of catalysts and selection of (co)solvent/substrate/base for optimized reaction conditions. We also investigated the influence of the ligand backbone and the functionalization of donor and backbone sites in the ligand. Our analysis reveals the crucial role of the second coordination sphere functionalization for the reactivity of the complexes with impact in some cases exceeding that of the variation of the functional groups directly attached to the donor atoms.

Alkoxycarbonylations are important and versatile reactions that result in the formation of a new C-C bond. Herein, we report on a new and halide-free alkoxycarbonylation reaction that does not require the application of an external carbon monoxide atmosphere. Instead, manganese carbonyl complexes and organo(alkoxy)borate salts react to form an ester product containing the target C-C bond. The required organo(alkoxy)borate salts are conveniently generated from the stoichiometric reaction of an organoborane and an alkoxide salt and can be telescoped without purification. The protocol leads to the formation of both aromatic and aliphatic esters and gives complete control over the ester's substitution (e.g., OMe, OtBu, OPh). A reaction mechanism was proposed on the basis of stoichiometric reactivity studies, spectroscopy, and DFT calculations. The new chemistry is particularly relevant for the field of Mn(I) catalysis and clearly points to a potential pathway toward irreversible catalyst deactivation.

Selectivity control is one of the most important functions of a catalyst. In asymmetric catalysis the enantiomeric excess (e.e.) is a property of major interest, with a lot of effort dedicated to developing the most enantioselective catalyst, understanding the origin of selectivity, and predicting stereoselectivity. Herein, we investigate the relationship between predicted selectivity and the uncertainties in the computed energetics of the catalytic reaction mechanism obtained by DFT calculations in a case study of catalytic asymmetric transfer hydrogenation (ATH) of ketones with an Mn-diamine catalyst. Data obtained from our analysis of DFT data by microkinetic modeling is compared to results from experiment. We discuss the limitations of the conventional reductionist approach of e.e. estimation from assessing the enantiodetermining steps only. Our analysis shows that the energetics of other reaction steps in the reaction mechanism have a substantial impact on the predicted reaction selectivity. The uncertainty of DFT calculations within the commonly accepted energy ranges of chemical accuracy may reverse the predicted e.e. with the non-enantiodetermining steps contributing to e.e. deviations of up to 25 %.

The reaction medium and conditions are the key parameters defining the efficiency and performance of a homogeneous catalyst. In the state-of-the-art molecular descriptions of catalytic systems by density functional theory (DFT) calculations, the reaction medium is commonly reduced to an infinitely diluted ideal solution model. In this work, we carry out a detailed operando computational modeling analysis of the condition dependencies and nonideal solution effects on the mechanism and kinetics of a model ester hydrogenation reaction by a homogeneous Mn(I)-P,N catalyst. By combining DFT calculations, COSMO-RS solvent model, and the microkinetic modeling approach, the kinetic behavior of the multicomponent homogeneous catalyst system under realistic reaction conditions was investigated in detail. The effects of the reaction medium and its dynamic evolution in the course of the reaction were analyzed by comparing the results obtained for the model methyl acetate hydrogenation reaction in a THF solution and under solvent-free neat reaction conditions. The dynamic representations of the reaction medium give rise to strongly nonlinear effects in the kinetic models. The nonideal representation of the reaction medium results in pronounced condition dependencies of the computed energetics of the elementary reaction steps and the computed kinetic profiles but affects only slightly such experimentally accessible kinetic descriptors as the apparent activation energy and the degree of rate control.