Mechanism of Ligand Exchange Processes for Titanocene Complexes: A Computational Study

The ligand exchange mechanisms of titanocene complexes were investigated by using density functional theory (DFT) to elucidate the reactivity trends of halogenation and deprotection reactions involving dithiolate-substituted species. Specifically, the transformations of titanocene dithiolate into dichloride and difluoride complexes via HCl, HF, and XeF2 were examined. The study reveals that these processes follow an associative interchange (Ia) mechanism, with significant differences in activation barriers and intermediates depending on the halogen source. While HCl-mediated substitution proceeds through defined multistep pathways with moderate activation energies, HF requires higher activation energy and slower reaction rates. In contrast, XeF2 enables a radical-mediated pathway characterized by near-barrierless energy profiles, explaining its experimentally observed rapid fluorination. Additionally, the reverse reaction, formation of the dithiolate complex from titanocene dichloride, was shown to be thermodynamically unfavorable without base-mediated deprotonation. This comprehensive analysis underscores the role of ligand electronics and the unique reactivity of XeF2, offering mechanistic insights that may aid future applications of titanocenes in positron emission tomography (PET) imaging and medicinal chemistry.