Since the C₆₀ discovery in 1985, many fullerene structures have been synthesized and a variety of experimental and computational studies regarding the fullerene stability, characterization, properties such as aromaticity, and reactivity have been reported.¹ The huge interest engendered by these fullerene-based materials is mainly attributed to their potential applications in the electronics, photovoltaics, biology, and medicine fields. Obstacles to such bio-applications include their poor solubility in water necessitating the preparation of water-soluble materials by suitable modifications. One of the most useful methods to functionalize fullerenes is via 1,3-dipolar cycloaddition (i.e. Prato reaction). The complete structural, chemical and electronic properties of (metallo)fullerenes are not totally understood at the present time. Specifically, the factors controlling the regiochemistry of multiple additions remain largely unexplored and poorly understood. In this communication, we rationalize using DFT calculations both the effect of the exohedral moiety and the orientation of the encapsulated cluster on the regioselectivity of the Prato (bis)addition to the I_h-C₈₀ based endohedral metallofullerenes, M₃N@I_h-C₈₀ (M=Sc, Lu, Y, and Gd).^2-4

¹M. Garcia-Borràs, S. Osuna, M. Swart, J. M. Luis, M. Solà, Chem. Soc. Rev., 2014, 43, 5089.

²S. Aroua, M. Garcia-Borràs, S. Osuna, Y. Yamahoshi, Chem. Eur. J. 2014, 20, 14032.

³S. Aroua, M. Garcia-Borràs, M. Bölter, M., S. Osuna, Y. Yamakoshi, J. Am. Chem. Soc. 2015, 137, 58.

⁴M. R. Cerón, M. Izquierdo, M. Garcia-Borràs, S. S. Lee, S. Osuna, L. Echegoyen, J. Am. Chem. Soc. 2015, 137, 11775.