Weak C-H/π Interaction Participates in the Diastereoselectivity of a Host-Guest Complex in the Presence of Six Strong Hydrogen Bonds Antonio Frontera,* Carolina Garau, David Quin ˜ onero, Pablo Ballester, Antoni Costa, and Pere M. Deya `* Departament de Quı ´mica, UniVersitat de les Illes Balears, Crta. de Valldemossa km 7.5, 07122 Palma de Mallorca, Spain tonif@soller.uib.es Received February 12, 2003 ABSTRACT We report a study of the interaction between methylmethanetriacetic acid (MMTA) and a tripodal amidopyridine receptor 1, where the geometry of the binding is in part governed by a weak C-H/π interaction in the presence of six strong N(O)-H‚‚‚O(N) hydrogen bonds. There are two possible binding geometries for the 1:1 complex 1‚MMTA; combining computational and experimental evidence we demonstrate that the endo binding mode is more favorable as the result of a C-H/π interaction. The C-H/π interaction 1 can be defined as the attraction between the C-H bond and the π system 2 and has recently gained attention in the consideration of a variety of molecular phenomena. Despite being the weakest among the hydrogen bonds, it has been found in a variety of substances to play important roles in their physical, chemical, and biological properties. 3-6 Whereas the enthalpy for a “conventional hydrogen bonds” is within the range of 3-7 kcal/mol, the one for a one-pair C-H/π interaction is presumed to be less than 1 kcal/mol. 7 The total energy of the interaction is increased by organizing CHs or π-groups into favorable structures. This point is important in understanding the role of weak interactions. Hunter’s group 8 has used an amide macrocycle with a highly preorganized cavity containing both polar and nonpolar recognition sites to form stable complexes with cyclic peptides in water via hydrogen-bonds, N-H/ π, and C-H/π interactions. Some of us have previously reported 9 a synthetic meth- odology for preparing 1,3,5-triaryl-substituted benzenes in multigram quantities. In this letter, we report a study of the interaction between methylmethanetriacetic acid (MMTA) and a tripodal amidopyridine receptor 1, where the geometry (1) Kodama, Y.; Nishihata, K.; Nishio, M.; Nakagawa, N. Tetrahedron Lett. 1977, 18, 2105. (2) Nishio, M.; Hirota, M.; Umezawa, Y. The C-H/π Interaction. EVidence, Nature, and Consequences; Wiley-VCH, Inc.: New York, 1998. (3) Quiocho, F. A.; Vyas, N. K. Nature 1984, 310, 381. (4) Vyas, N. K.; Vyas, M. N.; Quiocho, F. A. Nature 1987, 327, 635. (5) Umezawa, Y.; Tsuboyama, S.; Takahashi, H.; Uzawa, J.; Nishio, M. Tetrahedron 1999, 55, 10047. (6) Amabilino, D. B.; Ashton, P. R.; Balzani, V.; Boyd, S. E.; Credi, A.; Lee, J. Y.; Menzer, S.; Stoddart, J. F.; Venturi, M.; Williams, D. J. J. Am. Chem. Soc. 1998, 120, 4295. (7) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Mikami, M.; Tanabe, K. J. Am. Chem. Soc. 2000, 122, 3746. (8) Allot, C.; Bernard, P. L.; Hunter, C. A.; Rotger, C.; Thomas, J. A. Chemm. Commun. 1998, 2449. (9) Rotger, M. C.; Costa, A.; Saa ´, J. M. J. Org. Chem. 1993, 58, 4083. ORGANIC LETTERS 2003 Vol. 5, No. 7 1135-1138 10.1021/ol034247n CCC: $25.00 © 2003 American Chemical Society Published on Web 03/14/2003