From Boron Flatland to 3D Pharmacophore Space: Tacn-Supported Boronium Cage Cations

Replacement of C–C bonds with isoelectronic B–N units offers a compelling yet underdeveloped strategy for modulating molecular structure and electronic properties. Here we report that tacn-family ligands (1,4,7-triazacyclononane and its N-alkyl derivatives) enable the straightforward assembly of polycyclic boronium(+2) cations through a simple one-pot reaction with Me 2 SBHBr 2 under ambient conditions. These reactions produce rigid cage structures in which three fused five-membered rings are formed in a single step via tridentate coordination of the ligand to a [BH] 2+ core. The resulting boronium salts are readily isolated and exhibit remarkable thermal and aqueous stability, as demonstrated by multinuclear NMR spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. In the parent system, the N–H groups display Brønsted acidity (pKa1 ≈ 3.2) while maintaining structural integrity, with reversible protonation/deprotonation behavior observed. Electrostatic potential analyses reveal that substitution of B–N linkages for C–C bonds preserves overall molecular topology while substantially altering surface electron density, underscoring the utility of B–N/C–C isosterism for tuning intermolecular interactions. Limiting ligand donation to a bidentate mode affords a related bicyclic boronium(+1) framework containing a tertiary amine, whose geometry, reduced basicity (pKb1 ≈ 8.7), and reactivity of which are strongly influenced by the adjacent cationic boron center. Protonation yields a dication featuring a short N–H···H–B distance consistent with a dihydrogen bond, and thermal H 2 elimination cleanly generates the parent tridentate boronium cage. These findings demonstrate that tacn ligands provide a general and operationally simple route to robust boronium-based cage architectures. The resulting three-dimensional, electrostatically tunable frameworks expand the accessible structural space of organoboron chemistry and suggest potential utility as scaffolds in applications where shape and charge distribution are critical, including molecular recognition and pharmacophore design.