The Impact of Computational Uncertainties on the Enantioselectivity Predictions

The Impact of Computational Uncertainties on the Enantioselectivity Predictions: A Microkinetic Modeling of Ketone Transfer Hydrogenation with a Noyori-type Mn-diamine Catalyst

Krieger, A.M. (TU Delft ChemE/Inorganic Systems Engineering)
Pidko, E.A. (TU Delft ChemE/Algemeen; TU Delft ChemE/Inorganic Systems Engineering)

2021

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 %.

density functional theory
enantioselectivity
microkinetic modeling
Noyori-type catalysis
transfer hydrogenation

http://resolver.tudelft.nl/uuid:43f7282e-3f28-45ab-8fee-9640dd7c15e7

https://doi.org/10.1002/cctc.202100341

1867-3880

ChemCatChem, 13 (15), 3517-3524

Institutional Repository

journal article

© 2021 A.M. Krieger, E.A. Pidko