Multitask prediction of site selectivity in aromatic C-H functionalization reactions
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...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
2020
|
| Online Access: | https://hdl.handle.net/1721.1/125612 |
| _version_ | 1811096475257536512 |
|---|---|
| author | Struble, Thomas J Coley, Connor Wilson Jensen, Klavs F |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Struble, Thomas J Coley, Connor Wilson Jensen, Klavs F |
| author_sort | Struble, Thomas J |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:44:16Z |
| format | Article |
| id | mit-1721.1/125612 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:44:16Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | mit-1721.1/1256122022-09-29T21:09:33Z Multitask prediction of site selectivity in aromatic C-H functionalization reactions Struble, Thomas J Coley, Connor Wilson Jensen, Klavs F Massachusetts Institute of Technology. Department of Chemical Engineering 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. 2020-06-02T16:49:18Z 2020-06-02T16:49:18Z 2020-04 2020-02 Article http://purl.org/eprint/type/JournalArticle 2058-9883 https://hdl.handle.net/1721.1/125612 Struble, Thomas J., Connor Wilson Coley, and Klavs F. Jensen, "Multitask prediction of site selectivity in aromatic C-H functionalization reactions." Reaction Chemistry & Engineering 5 (Apr. 2020): no. 896 doi 10.1039/D0RE00071J ©2020 Author(s) 10.1039/D0RE00071J Reaction Chemistry & Engineering Creative Commons Attribution Noncommercial 3.0 unported license https://creativecommons.org/licenses/by-nc/3.0/ application/pdf Royal Society of Chemistry (RSC) |
| spellingShingle | Struble, Thomas J Coley, Connor Wilson Jensen, Klavs F Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title | Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title_full | Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title_fullStr | Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title_full_unstemmed | Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title_short | Multitask prediction of site selectivity in aromatic C-H functionalization reactions |
| title_sort | multitask prediction of site selectivity in aromatic c h functionalization reactions |
| url | https://hdl.handle.net/1721.1/125612 |
| work_keys_str_mv | AT strublethomasj multitaskpredictionofsiteselectivityinaromaticchfunctionalizationreactions AT coleyconnorwilson multitaskpredictionofsiteselectivityinaromaticchfunctionalizationreactions AT jensenklavsf multitaskpredictionofsiteselectivityinaromaticchfunctionalizationreactions |