Theoretical Study of the Highly Diastereoselective 1,3-Dipolar Cycloaddition of 1,4-Dihydropyridine-Containing Azomethine Ylides to [60]Fullerene (Prato’s Reaction) Amaury Alvarez, †,‡ Estael Ochoa, † Yamila Verdecia, † Margarita Sua ´ rez,* ,† Miquel Sola ´,* ,§ and Nazario Martı ´n* ,| Laboratorio de Sı ´ntesis Orga ´ nica, Facultad de Quı ´mica, Universidad de La Habana, 10400 Ciudad Habana, Cuba, Instituto Cubano de Investigaciones de los Derivados de la Can ˜ a de Azu ´ car, P.O. Box 4026, Ciudad Habana, Cuba, Institut de Quı ´mica Computacional and Departament de Quı ´mica, Universitat de Girona, 17071 Girona, Catalonia, Spain, and Departamento de Quı ´mica Orga ´ nica, Facultad de Quı ´mica, Universidad Complutense, 28040 Madrid, Spain msuarez@fq.uh.cu; nazmar@quim.ucm.es; miquel.sola@udg.es Received November 25, 2004 The 1,3-dipolar cycloaddition of azomethine ylides bearing the biologically active 1,4-dihydropiridine ring to C 60 was investigated by means of quantum mechanical calculations at the semiempirical AM1 and DFT (B3LYP/6-31G*) methods. The presence of two chiral centers and one chiral axis in the resulting fulleropyrrolidines leads to four possible [6,6] cycloaddition products. Formation of atropoisomers has also been considered. The transition-state structures were computed for the four different cycloaddition pathways to find out the lowest activation energy stereoisomer. In all cases, a frequency analysis and an IRC calculation were carried out to fully characterize the located transition-state structures. AM1 results and single-point energy calculations at the B3LYP/6-31G*// AM1 level for the four transition-state structures yield activation energies values below 5 kcal/ mol. Introduction The surge of interest in fullerenes chemistry has extensively been focused on the functionalization of C 60 , the most abundant and representative of fullerenes. The chemical derivatization of fullerenes still represents an important challenge in current chemical research, and among the wide variety of organofullerenes synthesized by simple and accessible synthethic routes, the family of fulleropyrrolidines has played a prominent role provided that they retain the basic fullerene properties and are commonly soluble in organic solvents. 1 The electron-deficient character of C 60 stems from its low-lying LUMO, and therefore, all embedded olefins ([6- 6]-ring junctions) in the fullerene cage behave as strong electrophiles, which prompted the development of nu- merous efficient cycloadditions. 2,3 Among them, one of the most used and successful reactions has been the 1,3 † Universidad de La Habana. ‡ Instituto Cubano de Investigaciones de los Derivados de la Can ˜a de Azu ´ car. § Universitat de Girona. | Universidad Complutense. (1) Tagmatarchis, N.; Prato, M. Synlett 2003, 768. (2) (a) Hirsch, A.; Brettreich, M.; Wuld, F. Fullerenes: Chemistry and Reactions; John Wiley and Sons Ltd.: New York, 2004. (b) Diederich, E.; Thilgen, C. Science 1996, 271, 317. (c) Hirsch, A. Fullerenes and Related Structures; Springer: Berlin, 1999. (d) Fullerenes and Related Structures; Hirsch, A., Ed. Top. Curr. Chem. 1999, 199, 1. 3256 J. Org. Chem. 2005, 70, 3256-3262 10.1021/jo0479009 CCC: $30.25 © 2005 American Chemical Society Published on Web 03/26/2005