Determination of the Effect of Cation-π Interactions on the Stability of r-Oxy-Organolithium Compounds Pablo Monje, † M. Rita Paleo, † Luis Garcı ´a-Rı ´o, ‡ and F. Javier Sardina* ,† Departamento de Quı ´mica Orga ´nica and Departamento de Quı ´mica Fı ´sica, UniVersidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain jaVier.sardina@usc.es ReceiVed May 30, 2008 Sn-Li exchange equilibria have allowed the quantification of the stabilizing effect of cation-π interactions in organo- lithium chemistry. Stabilization energy data on the effect of Li-π complexation of an aromatic ring or a CdC double bond in organolithium compounds are presented. The amount of stabilization gained by complexation of the Li atom with a π system in R-oxy-organolithium compounds is quite comparable to the one observed in systems containing Li-N or Li-O interactions. Noncovalent interactions involving unsaturated systems 1 play a dominant role in many forefront areas of modern chemistry 2 and molecular biology. 3 Together with other attractive interac- tions, cation-π interactions 4 are playing a key role in both chemical and biological recognition, 1,5 the structural and functional properties of proteins, 6 and enzymatic catalysis. 7 The cation-π interaction is fundamentally an electrostatic interaction between a positively charged species (a cation) and the electrons that make up one or more π bonds. Theoretical investigations 8 and experimental evidence 9 for cation-π interactions are well- documented and place it among the strongest of noncovalent binding forces. From a synthetic point of view, cation-π interactions have been occasionally proposed to explain the stereochemical outcome of several organic transformations. 10 For instance, five-membered rings have been prepared in a very stereoselective manner by anionic cyclizations of different alkenyllithiums. 11 The stereoselectivity of this reaction is a consequence of an energetically favorable coordination of the lithium atom with the remote π bond. More recent applications 12 of cation-π interactions include their use as a conformation- controlling tool 13 in a variety of regio- and stereoselective syntheses, as well as in the design of chiral metal catalysts for enantioselective Diels-Alder and Mukaiyama-Michael reac- tions. 14 We have recently reported 15 the measurement of the relative stabilities of R-heterosubstituted benzylic organolithium com- pounds and secondary R-oxy-organolithium compounds in THF, where the effects of alkyl substituents and Li-O and Li-N chelation on carbanion stability were quantified. Our approach is based on the establishment of a Sn-Li exchange between the organolithium under study and a reference compound (as shown in eq 1 in Figure 1), an equilibrium reaction which favors the pairing of the most stable carbanion with the more electropositive Li atom. 16,17 † Departamento de Quı ´mica Orga ´nica. ‡ Departamento de Quı ´mica Fı ´sica. (1) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. 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