Carbanions, generally involved as ion pairs or aggregates, are important intermediates in the organic synthesis of many biologically active natural products, pharmaceuticals, drugs, etc. A common synthetic procedure is the metallation of a substrate with an alkyl lithium or lithium amide in an ether followed by reaction with a suitable electrophile. We propose to put this largely empirical technique on quantitative scientific basis by continuing our determination of equilibrium constants for the reactions, R M + R'H = R'M + RH, for indicator hydrocarbons (e.g., fluorenes, arylmethanes, etc.) in tetrahydrofuran (THF) with cesium and lithium as gegenions. These indicator systems will be used to determine equilibria for carbon acids with various functional groups important in synthesis: vinyl, allyl, benzyl and aryl compounds, sulfur derivatives, silicon and phosphorus compounds, amides, ethers, heterocyclic compounds dianions and enolate ions. Determinations as a function of temperature will provide thermodynamic quantities and comparison of the cesium equilibria, which are known to involve contact ion pairs, with the corresponding lithium equilibria, in which a variety of types of ion pairs are possible, will facilitate understanding of the more complex lithium cases. Conductivity studies will relate the ion pairs to dissociated ions. The results will be interpreted with the help of related kinetic acidity measurements, studies of aggregated systems, theoretical quantum chemical calculations and computer graphics analysis of electron density distributions.
| Streitwieser, Andrew (2009) Perspectives on computational organic chemistry. J Org Chem 74:4433-46 |
| Streitwieser, Andrew; Husemann, Marc; Kim, Yeong-Joon (2003) Aggregation and reactivity of the dilithium and dicesium enediolates of 1-naphthylacetic acid. J Org Chem 68:7937-42 |
| Facchetti, A; Kim, Y J; Streitwieser, A (2000) Comparisons of ion pair acidities of some acidic carbon acids. J Org Chem 65:4195-7 |
| Kim, Y J; Streitwieser, A; Chow, A et al. (1999) Aggregation and C-N rotation of the lithium salt of N,N-dimethyldiphenylacetamide. Org Lett 1:2069-71 |
| Streitwieser, A; Leung, S S; Kim, Y J (1999) Role of aggregates in Claisen acylation reactions of imidazole, pyrazole, and thioesters with lithium enolates in THF. Org Lett 1:145-7 |
