Fluorovinyl thioethers as putative steric and electronic thioester enolate mimetics: chemoselective HF addition to acetylene thioethers

Fluorovinyl thioethers are presented as a putative biomimetic surrogate for the enol/ate of a thioester. A method is explored for the preparation of fluorovinyl thioethers by treatment of acetylene thioethers with pyridinium (poly)-hydrogen fluoride. Titration with pyridine is important for the selectivity of the reaction. Without titration the corresponding gem-difluoroethyl thioethers are generated. With titration the hydrofluorination reaction can be stopped at an intermediate stage to recover the fluorovinyl thioether, which is a relatively stable functionality to purification and manipulation. Preliminary density functional theory calculations indicate that the fluorovinyl thioether motif shares a comparable steric and electronic profile to a thioester enol. A fluorovinyl thioether representing the terminus of the pantothenoyl chain of acetyl-CoA is prepared as a relevant biomimetic example.