Structural Factors Controlling the Aggregation of Lithium Phenolates in Weakly Polar Aprotic Solvents

The structures of lithium 4-fluoro-, 4-chloro, 2and 4-bromo-, 4-(trifluoromethy1)-, 4-methoxy-, 2-methyl-, 2-ethyl-, 2-n-propyl-, 2-isopropyl-, 2-tert-butyl-, 2-(methoxymethyl), 3,5-dimethyl-, 3,5-dimethyl-4-methoxy-, 4-chloro-3,5-dimethyI-, 3,5-diethyl-, and 3,5-dimethoxyphenolates in solution in weakly polar, aprotic solvents such as pyridine, tetrahydrofuran, dimethoxyethane, 1,3-dioxolane, diethyl ether, 2,6-lutidine, and triethylamine have been established by 13C NMR spectroscopy. Para substituents influence the equilibrium between dimer and tetramer through their effect on the basicity of the anion. @Alkyl substituents promote dimer formation through steric effects in the order of their steric bulk. The 2-methoxymethyl group stabilizes the tetramer. Dimers are favored relative to tetramers by a combination of high Lewis basicity and low steric demand of the solvent. A number of lithium phenolates in 1,3-dioxolane exist as hexamers at low temperatures. The following pairs of values for AH (kcal mol-I) and A S (cal mol-] K-') are found for 2 dimer * tetramer: lithium 4-bromophenolate (THF), 4.4 f 0.5,24 & 2; 3,5-dimethylphenolate (pyridine), 6.6 f 0.2, 33 f 1; 2-isopropylphenolate (THF), 7.5 f 0.5, 38 f 2. For tetramer * 2/3 hexamer the values for 3,5-dimethoxyphenolate (dioxolane) are -4.7 f 0.3 and -20 & 1.7. 'Li quadrupole splitting constants have been determined for several dimers and tetramers. Many important synthetic methodologies involve the reactions of organic lithium salts with electrophiles in weakly polar aprotic solvents, particularly ethers. The nucleophiles in these reactions are usually ambident anions (e.g. enolate,' enamide? heterosubstituted allyl3), the corresponding lithium salts of which are contact ion pairs or ion-pair aggregates. There is evidence that such ion-pair aggregates can function a s true reactant^,^^ and it is, therefore, probable that the degree of aggregation influences reactivity and regioand stereochemistry. An understanding of the structural factors that control the degree of aggregation together with some knowledge of the thermodynamics of aggregation equilibria are, therefore, prerequisites for any mechanistic studies of this important group of reactions. The main driving force for aggregation in weakly polar solvents is, of course, the maximization of electrostatic interactions between cations and anions. Aggregation, however, will generally occur a t the expense of solvation of the ions, which, for weakly polar donor solvents, will principally involve the lithium cation. The overall process may, therefore, be viewed as a competition between anions and solvent for the available coordination sites (usually three or four) around the lithium cation and will thus reflect their Lewis basicities. In addition to considerations of intrinsic basicity, (1) Jackman, L. M.; Lange, B. C. Tetrahedron 1977, 33, 2737. (2) Evans, D. A. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: New York, 1984; p 1. Whitesell, J. K.; Whitesell, M. A. Synthesis 1983, 517. ( 3 ) Seebach, D. Angew. Chem., Int . Ed. Engl. 1979, 18,239. Hoppe, D. Ibid. 1984, 23, 932. (4) Jackman, L. M.; Lange, B. C . J . Am. Chem. Sor. 1981, 103, 4494. Jackman, L. M.; Dunne, T. S . Ibid. 1985, 107, 2805. (5) Seebach, D. Proceedings of The Robert A. Welch Foundation Conferences on Chemical Research, Houston, TX, 1984. (6) McGarrity, J. F.; Ogle, C. A. J . Am. Chem. Soc. 1985, 107, 1805. steric factors involving solvent and anion will be important. It might also be supposed that the number of lone pairs on the donor atoms of the anion could effect aggregation since in the cubic tetramer 1, for example, a total of three lone pairs can be directed