The organic chemist’s toolbox is vast, with technologies to accelerate the synthesis of novel chemical matter. The field of asymmetric catalysis is one approach to accessing new areas of chemical space and computational power is today sufficient to assist in this exploration. Unfortunately, existing techniques generally require computational expertise and are therefore underutilized in synthetic chemistry. Here we present our platform Virtual Chemist, which allows bench chemists to predict outcomes of asymmetric chemical reactions ahead of testing in the laboratory, in just a few clicks. Modular workflows facilitate the simulation of various sets of experiments, including the four realistic scenarios discussed: one-by-one design, library screening, hit optimization and substrate-scope evaluation. Catalyst candidates are screened within hours and the enantioselectivity predictions provide substantial enrichments compared to random testing. The achieved accuracies within ~1 kcal mol–1 provide opportunities for computational chemistry in the field of asymmetric catalyst design, allowing bench chemists to guide the design and discovery of asymmetric catalysts.
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The sets of molecules used in this study (Supplementary Tables 1–8) and representative computed data (Supplementary Tables 9–18) are available as Supplementary Information. A tutorial for the use of this platform is provided as Supplementary Data 1. The programs are available (free of charge for academic research) at www.molecularforecaster.com. All the data, parameter files and structures are available on moitessier-group.mcgill.ca/software.html.
All other data is available from the authors upon reasonable request.
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We thank NSERC (Discovery programme) for financial support. Calcul Québec and Compute Canada are acknowledged for generous CPU allocations.
Virtual Chemist is distributed by Molecular Forecaster (free of charge for academic research) co-founded by N.M. (CEO: J.P.).
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Burai Patrascu, M., Pottel, J., Pinus, S. et al. From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis. Nat Catal 3, 574–584 (2020). https://doi.org/10.1038/s41929-020-0468-3
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