Pedro Zamora YatesKlaus BiegerVasquez, DavidDavidVasquez2025-10-102025-10-102025222860https://hdl.handle.net/20.500.12740/23469Phosphorylated heterocycles constitute an interesting class of molecules featuring complex, often unproven reaction mechanisms. Their synthesis is approached through experimental trial-and-error methods. Here we present a theoretical study of the reaction mechanism leading to the formation of thiazaphospholidine, as an example of such compounds. Our results reveal that proton rearrangement, rather than nucleophilic attack, plays a significant role in the rate-determining step of the reaction. This insight allows the prediction of which isomer will form from unsymmetrical reagents, potentially leading to more efficient experimental procedures for producing tailor-made structures that exhibit desired properties. We demonstrate that seemingly simple reactions, such as the nucleophilic substitution of an amino group on trivalent phosphorus, may require a more intricate explanation involving less favored tautomeric structures and a multi-step approach and are therefore not completely intuitive. © 2024 Elsevier B.V., All rights reserved.restrictedAccessACTIVATION ENERGYCYCLIZATIONDFTFUKUI-FUNCTIONPHOSPHACYCLERDGTAUTOMERSCYCLIZATIONSEXPERIMENTAL TRIALSFUKUI FUNCTIONSHETEROCYCLESPHOSPHACYCLESREACTION MECHANISMTAUTOMERTRIAL-AND-ERROR METHODArtículo https://doi.org/10.1016/j.molstruc.2024.139492