Moving forward, e orts to refine the initial guess structures in our computational workflow could reduce the number of reactions requiring manual review, thereby improving the overall e iciency and e ectiveness of the screening process. Additionally, expanding our database to include more substituents could provide deeper insights into the structure-reactivity relationships that govern these bioorthogonal reactions. The datasets generated from this and expanded study will also prove invaluable for machine learning applications aimed at predicting and optimizing bioorthogonal reactions.