DOI: 10.1002/chem.201200940 Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M 3 N@C 80 (M = Sc, Lu, Gd): The D 5h versus I h Isomer and the Influence of the Metal Cluster Sílvia Osuna, [b] Ramón Valencia, [a] Antonio Rodríguez-Fortea,* [a] Marcel Swart,* [c, d] Miquel Solà,* [c] and Josep M. Poblet* [a] Introduction Endohedral metallofullerenes (EMFs), that is, those ful- lerenes that contain metal atoms or metal clusters in their interior, have attracted increasing attention over the last few years due to their potential applications in different fields such as medicine or materials science. [1] Since the first detec- tion of La@C 60 twenty-five years ago, [2] many different fami- lies of EMFs have been characterized. In 1999, Dorn and co-workers reported the synthesis, isolation, and characteri- zation of Sc 3 N@I h -C 80 , [3] which is the third most abundant fullerene after C 60 and C 70 and the prototype of the family of nitride EMFs. Many other fullerenes that contain the tri- metallic nitride unit have been prepared and characterized so far with carbon cages that range from C 68 to C 104 and with metal atoms that are generally from Group 3 or lantha- nides. [1b, c] The electronic structure of the nitride EMFs can be easily understood from the ionic model if we consider that a formal transfer of six electrons from the internal guest to the carbon cage takes place, (M 3 N) 6 + @ACHTUNGTRENNUNG(C 2n ) 6 . Within this simple model, an orbital rule for predicting the most appropriate carbon-cage isomers to encapsulate a metal nitride was proposed by Poblet and co-workers. [4] The authors showed that the large HOMO–LUMO gap ob- served in nitride EMFs, which confers stability upon them, can be estimated from the energy gap between the LUMO+3 and the LUMO+2 in the empty cages. Popov and Dunsch showed that, in general, the stabilities of C 2n 6 and M 3 N@C 2n match, thereby confirming the validity of the ionic model. [5] The molecular orbital rule, although very useful, does not provide the physical explanation for the se- lection of a particular host C 2n cage by a given metal cluster. Recently, it has been shown that the relative stabilities of Abstract: In this work a detailed inves- tigation of the exohedral reactivity of the most important and abundant en- dohedral metallofullerene (EMF) is provided, that is, Sc 3 N@I h -C 80 and its D 5h counterpart Sc 3 N@D 5h -C 80 , and the (bio)chemically relevant lutetium- and gadolinium-based M 3 N@I h /D 5h -C 80 EMFs (M = Sc, Lu, Gd). In particular, we analyze the thermodynamics and ki- netics of the Diels–Alder cycloaddition of s-cis-1,3-butadiene on all the differ- ent bonds of the I h -C 80 and D 5h -C 80 cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc 3 N@C 80 . After- wards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D 5h -b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, I h -a, is the most reactive bond in M 3 N@D 5h -C 80 regardless of M. Sc 3 N@C 80 and Lu 3 N@C 80 give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M = Gd, as previ- ously found in similar metalloful- lerenes. Calculations also show that the D 5h isomer is more reactive from the kinetic point of view than the I h one in all cases which is in good agreement with experiments. Keywords: cycloaddition · density functional calculations · Diels– Alder reaction · fullerenes · ther- modynamics [a] Dr. R. Valencia, Dr. A. Rodríguez-Fortea, Prof. J.M. Poblet Departament de Química Física i Inorgànica Universitat Rovira i Virgili, c/Marcel·lí Domingo s/n Campus Sescelades, 43007 Tarragona (Spain) E-mail: antonio.rodriguezf@urv.cat josepmaria.poblet@urv.cat [b] Dr. S. Osuna Department of Chemistry and Biochemistry University of California, Los Angeles 607 Charles E. Young Drive Los Angeles, CA 90095 (USA) [c] Prof. M. Swart, Prof. M. Solà Institut de Química Computacional i Departament de Química Universitat de Girona, Campus Montilivi s/n 17071 Girona (Spain) E-mail : marcel.swart@udg.edu miquel.sola@udg.edu [d] Prof. M. Swart Institució Catalana de Recerca i Estudis AvanÅats (ICREA) Pg. Lluís Companys 23, 08010 Barcelona (Spain) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201200940.  2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2012, 18, 8944 – 8956 8944