Titanocenes functionalization with high chemical diversity via titanium protecting groups

Titanocenes are well-recognized for their diverse applications in catalysis and biomedical research. Despite their potential, challenges related to stability and functionalization have limited broader utility, especially in medicinal chemistry. In this study, we present a strategy for the functionalization of titanocenes using a class of titanium protecting groups. This approach provides enhanced control over reactivity and significantly broadens the scope of structurally diverse modifications accessible for these complexes. Furthermore, we demonstrate the successful integration of a BODIPY fluorophore into titanocene-based systems, enabling advanced cellular imaging and visualizing the real perinuclear distribution of these organometallic compounds in living cell. The efficient incorporation of biomolecules such as biotin and cholesteryl derivatives through click-chemistry ligation underscores the potential of this method to facilitate the development of titanocene-based agents for pharmaceutical applications. By addressing previous limitations, this work paves the way for more effective utilization of titanocenes in both synthetic and biomedical fields. (Figure presented.)