Our study demonstrates that our fully automated quantum mechanics (QM)-based workflow reliably predicts the reaction site as observed experimentally with 70% correct predictions and 14.5% semi-correct predictions on the dataset provided by Tomberg et al. . Analysis of molecules where the reaction site was incorrectly predicted, particularly those with five potential sites, revealed that there might be issues with the underlying data in some cases. When only considering the lowest energy reaction site predicted by our workflow, we were able to achieve an accuracy of 78% on the same dataset. In contrast, a null model making random guesses would achieve only 38% accuracy, within a 95% confidence interval from 36 to 40%, underscoring our workflow's superior performance.