Carboxylate Catalyzed Isomerization of beta,gamma-Unsaturated N-Acetylcysteamine Thioesters

We demonstrate herein the capacity of simple carboxylate salts - tetrametylammonium and tetramethylguanidinium pivalate - to act as catalysts in the isomerization of beta,gamma-unsaturated thioesters to alpha,beta-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 beta,gamma-deuterated substrate. Computational analysis of the mechanism provides a similar value (k(1H)/k(1D)=1.05) with a mechanism where gamma-reprotonation of the enolate intermediate is rate determining.