Issue 34, 2024

Probing machine learning models based on high throughput experimentation data for the discovery of asymmetric hydrogenation catalysts

Abstract

Enantioselective hydrogenation of olefins by Rh-based chiral catalysts has been extensively studied for more than 50 years. Naively, one would expect that everything about this transformation is known and that selecting a catalyst that induces the desired reactivity or selectivity is a trivial task. Nonetheless, ligand engineering or selection for any new prochiral olefin remains an empirical trial-error exercise. In this study, we investigated whether machine learning techniques could be used to accelerate the identification of the most efficient chiral ligand. For this purpose, we used high throughput experimentation to build a large dataset consisting of results for Rh-catalyzed asymmetric olefin hydrogenation, specially designed for applications in machine learning. We showcased its alignment with existing literature while addressing observed discrepancies. Additionally, a computational framework for the automated and reproducible quantum-chemistry based featurization of catalyst structures was created. Together with less computationally demanding representations, these descriptors were fed into our machine learning pipeline for both out-of-domain and in-domain prediction tasks of selectivity and reactivity. For out-of-domain purposes, our models provided limited efficacy. It was found that even the most expensive descriptors do not impart significant meaning to the model predictions. The in-domain application, while partly successful for predictions of conversion, emphasizes the need for evaluating the cost–benefit ratio of computationally intensive descriptors and for tailored descriptor design. Challenges persist in predicting enantioselectivity, calling for caution in interpreting results from small datasets. Our insights underscore the importance of dataset diversity with broad substrate inclusion and suggest that mechanistic considerations could improve the accuracy of statistical models.

Graphical abstract: Probing machine learning models based on high throughput experimentation data for the discovery of asymmetric hydrogenation catalysts

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Article information

Article type
Edge Article
Submitted
03 Jūn. 2024
Accepted
15 Jūl. 2024
First published
16 Jūl. 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 13618-13630

Probing machine learning models based on high throughput experimentation data for the discovery of asymmetric hydrogenation catalysts

A. V. Kalikadien, C. Valsecchi, R. van Putten, T. Maes, M. Muuronen, N. Dyubankova, L. Lefort and E. A. Pidko, Chem. Sci., 2024, 15, 13618 DOI: 10.1039/D4SC03647F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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