Unveiling the synthesis of spirocyclic, tricyclic, and bicyclic triazolooxazines from intramolecular [3 + 2] azide-alkyne cycloadditions with a molecular electron density theory perspective

The intramolecular [3+2] cycloaddition (32CA) reactions of azido alkynes leading to spirocyclic, tricyclic, and bicyclic triazolooxazines has been studied within the molecular electron density theory (MEDT) at MPWB1K/6-311G(d,p) level. localization function (ELF) characterizes as zwitterionic species. Analysis conceptual DFT indices allows classifying azide moiety electrophilic counterpart alkyne nucleophilic one. These 32CA are under kinetic control with activation free energies 23.4–26.7 kcal mol−1. Along reaction path, pseudoradical centre is created initially C4, consistent Parr analysis; however, sequence bond formation controlled by energetically feasible six-membered oxazine ring. intermolecular interactions transition states were characterized from quantum atoms in molecules (QTAIM) study non-covalent interaction (NCI) gradient isosurfaces.