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Site_Selectivity.pdf (1.34 MB)

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

submitted on 27.08.2019, 12:56 and posted on 28.08.2019, 17:48 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.


ARO W911NF-16-2-0023

Machine Learning for Pharmaceutical Discovery and Synthesis Consortium (MLPDS)


Email Address of Submitting Author


Massachusetts Institute of Technology


United States

ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interests