Context-Aware Automated NMR Structure Elucidation

Frank Hu, Jonathan M. Tubb, Grant M. Rotskoff, Matthew W. Kanan, Thomas E. Markland

Machine learning approaches are rapidly revolutionizing the ability to analyze and extract structural insights from chemical data, enabling high-throughput chemical discovery. While existing data-driven approaches have shown remarkable promise for predicting chemical structures in the de novo setting, incorporating additional chemically informed context offers the opportunity to further improve these models' performance and extend their real-world utility. Here we provide a straightforward protocol to combine artificial-intelligence-based spectroscopic elucidation pipelines with contextual chemical data, e.g., known reactants or a desired product, by using automated retrosynthetic analysis to generate large training sets of molecules and contextual data in the form of synthetic precursors. We demonstrate our approach by showing that our recently introduced NMR structure elucidation framework can be trained to effectively leverage molecular precursor context. We show that when the chemical context provides useful information on the target molecule we obtain dramatically improved accuracy over using NMR spectra alone, obtaining Top-15 accuracies of up to 95.4% for molecules up to…