A novel synthetic route for the production of a variety of pyridine derived phosphonium salts was devised and the mechanism of this synthesis was elucidated using multiple spectroscopic methods and other techniques. 2-Vinylpyridine was combined with a number of substituted acid chlorides and various phosphines under conditions that were optimized to yield several different species containing the phosphonium and amide functionalities with an assortment of associated substitution patterns. Silica gel chromatography was used to isolate the phosphonium salts as well as a number of related intermediates produced in this synthesis, and these substances were analyzed using 1H, 13C, 31P and 2-DNMR experiments. The structures, lowest energy conformations and other aspects of the isolated intermediates and the final phosphonium salts produced were studied using geometry optimizations and related calculations run on Gaussian 09W software in order to explain unanticipated results regarding the collected spectroscopic data, as well as observations concerning the mechanism of this series of reactions.The synthesis appeared to occur via an unexpected and particularly interesting mechanism in which initial ketene formation resulted in protonation of the phosphine, followed by the addition of the newly formed phosphonium across 2-vinylpyridine. A highly concentration-sensitive nucleophilic attack by the pyridine moiety on the remaining excess acid chloride produced a doubly charged cationic species which quickly underwent deprotonation in the presence of water introduced during product isolation to give the final phosphonium salt. The pyridine derived phosphonium salts produced should make suitable intermediates in the synthesis of substituted indolizines via intramolecular Wittig reaction and follow up investigations are currently underway to find suitable conditions for these cyclization reactions.

Synthesis of phosphonium salt precursors to substituted indolizines

247th National Meeting (2014)

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