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Multitask Prediction of Site Selectivity in Aromatic C-H Functionalization Reactions

preprint
submitted on 27.08.2019 and posted on 28.08.2019 by Thomas J. Struble, Connor W. Coley, Klavs F. Jensen
Aromatic C-H functionalization reactions are an important part of the synthetic chemistry toolbox. Accurate prediction of site selectivity can be crucial for prioritizing target compounds and synthetic routes in both drug discovery and process chemistry. However, selectivity may be highly dependent on subtle electronic and steric features of the substrate. We report a generalizable approach to prediction of site selectivity that is accomplished using a graph-convolutional neural network for the multitask prediction of 123 C-H functionalization tasks. In an 80/10/10 training/validation/testing pseudo-time split of about 58,000 aromatic C-H functionalization reactions from the Reaxys database, the model achieves a mean reciprocal rank of 92%. Once trained, inference requires approximately 200 ms per compound to provide quantitative likelihood scores for each task. This approach and model allow a chemist to quickly determine which C-H functionalization reactions-if any-might proceed with high selectivity.

Funding

ARO W911NF-16-2-0023

Machine Learning for Pharmaceutical Discovery and Synthesis Consortium (MLPDS)

History

Email Address of Submitting Author

tstruble@mit.edu

Institution

Massachusetts Institute of Technology

Country

United States

ORCID For Submitting Author

0000-0003-1695-2367

Declaration of Conflict of Interest

No conflict of interests

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