Phosphonium Salt Ionic Liquids in Organic Synthesis (Sandwich Thesis)

Abstract

A survey of substitution reactions conducted in a phosphonium bistriflimide ionic liquid is presented. The results demonstrate high selectivity favoring substitution over typically competitive elimination and solvolytic processes even when challenging secondary and tertiary electrophiles are employed. The first reports of Kornblum substitution reactions in an ionic liquid are described that proceed with very high chemoselectivity in favor of nitro over nitroso products and elimination side products. The structure-reactivity study indicates that these reactions proceed through a narrow spectrum of pathways ranging from straight SN2 to a preassociation pathway along a saddle point that approaches the SN1 limit. The lack of any basic entity in the phosphonium bistriflimide ionic liquid appears to prevent any potential base-mediated elimination reactions, which makes this a highly selective medium for use in general substitution reactions. A general, high yielding procedure is described for the esterification of carboxylic acids through carboxylate alkylation in phosphonium salt ionic liquid. The product ester can be readily isolated using a standard extraction protocol or by direct solvent freedistillation allowing ionic liquid re-use. The reaction takes place at relatively low temperature in comparison to other processes reported in ionic liquids. Biologically important BZE (benzoate) esters were synthesized and a proposed solvolysis mechanism investigated in ionic liquids. The Pd-mediated Buchwald-Hartwig amination reaction of aryl halides in phosphonium salt ionic liquid consisting of a trihexyl(tetradecyl)phosphonium cation with a range of anions has been investigated. A pronounced anionic effect was uncovered with the reaction proceeding readily with weakly nucleophilic diarylamines only in the presence of non-coordinating anions. A mechanism is postulated to explain these results involving a rate limiting ligand exchange step that proceeds through a dissociative pathway. A novel non solvated crystal structure of tris(dibenzylideneacetone) palladium(0) in phosphonium salt ionic liquids is reported. This research provided insights concerning the use of ionic liquids in palladium catalyzed Buchwald-Hartwig amination reaction. New synthetic methods were developed for the preparation of trialkyl (methyl) phosphonium ionic liquids, with this novel "green" protocol, the use of iodomethane is eliminated and oxidation of trialkyl phosphines can be reduced.