Carboxylate Catalyzed Isomerization of β,γ-Unsaturated N-Acetylcysteamine Thioesters

Abstract

We demonstrate herein the capacity of simple carboxylate salts - tetrametylammonium and tetramethylguanidinium pivalate - to act as catalysts in the isomerization of β,γ-unsaturated thioesters to α,β-unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k_1H /k_1D =1.065±0.026) with a β,γ-deuterated substrate. Computational analysis of the mechanism provides a similar value (k_1H /k_1D =1.05) with a mechanism where γ-reprotonation of the enolate intermediate is rate determining.

Keywords: base catalysis; carboxylates; enolates; isomerization; kinetic isotope effects; reaction mechanism; thioesters.