Given the large number of possible non-equivalent bonds of Endohedral MetalloFullerenes (EMFs), the elucidation of the preferred addition sites for a target reaction is tremendously challenging.¹ The development of a set of simple rules able to rationalize the preferred regioselectivities by solely inspecting the fullerene structure would be extremely appealing for the whole fullerene community. This communication describes a set of predictive criteria called Predictive Aromaticity Criteria (PAC), to a priori identify the most reactive bonds of a given EMF towards the Bingel-Hirsch (BH) cycloaddition based on a simple evaluation of the cage structure, and without need to perform any expensive theoretical calculation or experimental measure.²

We take as starting point the investigation of the BH addition of diethylbromomalonate on all non-equivalent bonds of Sc₃N@D_3h-C₇₈ using density functional theory calculations. From the Sc₃N@D_3h-C₇₈ analysis, a set of rules that we called Predictive Aromaticity Criteria (PAC) is derived, which are further applied to predict the most favorable BH adducts for the challenging case of Sc₃N@D_5h-C₈₀. The predictions based on PAC are afterwards fully confirmed by both the computational and experimental results of the complete study of the regioselectivity of BH reaction to Sc₃N@D_5h-C₈₀. These results provide conclusive evidence on the reliability of the PAC, indicating that these rules are general and applicable to any BH reaction on IPR EMFs. Moreover, this work provides clear evidence of the key role played by the local aromaticity of the cage in EMF functionalization.^2-5

References:

[1] M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis and M. Solà, Chem. Soc. Rev., 2014, 43 (14), 5089

[2] M. Garcia-Borràs, M. R. Cerón, S. Osuna, M. Izquierdo, J.M. Luis, L. Echegoyen, M. Solà, submitted for publication, 2015.

[3] M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis and M. Solà, Chem. Commun., 2013, 49 (12), 1220

[4] M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis, L. Echegoyen, Miquel Solà, Chem. Commun., 2013, 49 (78), 8767

[5] M. Garcia-Borràs, S. Osuna, M. Swart, J.M. Luis and M. Solà, Angew. Chem. Int. Ed., 2013,  52 (35), 9275