Dramatic Concentration Depedence of Stereochemistry in the Wittig Reaction. Examination of the Lithium Salt Effect

Article abstract of DOI:10.1021/jo00367a010

The stereochemistry for Wittig reactions of butylidenetriphenylphosphorane (1) with benzaldehyde and hexanal was examined in detail with regard to concentration effects.For the reaction of 1 and benzaldehyde in the presence of LiBr, the proportion of trans-oxaphosphetane (measured by low-temperature 31P NMR) and (E)-alkene increased with respect to increasing reaction concentration in THF, approaching limiting values in a hyperbolic manner.Stereochemical drift, i.e., exaggerated production of (E)-alkene relative to trans-oxaphosphetane intermediate, was also concentration dependent, being more pronounced at higher concentrations.Experiments with varying amounts of lithium cation, and with NaBr instead of LiBr, demonstrated that this phenomenon is associated with the concentration of Li ion, which is increasingly sequestered by the THF solvent at higher dilution.In Me2SO, the dependence of alkene stereochemistry on concentration was greatly attenuated.In toluene, the concentration effect was inverted to some extent; more (E)-alkene was formed at higher dilution ( no betaines were observed by 31P NMR at low temperature).The reaction of 1 with hexanal in THF, in the presence of LiBr, exhibited a concentration depedence similar to that observed for the reaction with benzaldehyde ( at the oxaphosphetane stage).The rates of the lithium-dependent ("catalyzed") and lithium-independent ("uncatalyzed") reactions in the original carbon-carbon bond-forming step are ranked relative to each other, based on their concentration dependence in THF.For 1 and benzaldehyde in THF (with LiBr present), the catalyzed (k'') and uncatalyzed (k') rates constant have the following relative order: k₁'' = 5.2 and k₂'' = 2.5 mol^-2*dm⁶*s^-1; k₁' = 1.0 and k₂' < 0.02 mol_-1*dm³*s^-1 (see Scheme I and Appendix).Thus, at the representative concentrations of 0.05, 0.20, and 0.50 M, the original carbon-carbon bond-forming step in this Wittig reaction is 27percent, 61percent, and 79percent lithium catalyzed, respectively.