Hydrofluorination of Alkynes: From (E) to (Z)

Abstract

The hydrofluorination of alkynes is an efficient synthetic route to monofluoroalkenes or difluoroalkanes. Both fluorinated motifs have found applications in medicinal chemistry and beyond. This review explores the recent advances in the hydrofluorination of diverse alkynes through various activation methods, from classical coinage metal catalysis to metal‐free conditions. The range of alkynes goes from the simplest unactivated alkynes to activated ones (ynones and derivatives, ynamides, alkynyl sulfides and sulfones as much as haloalkynes). Regio‐ and stereoselective methods exists, but there is still room for improvement depending on the type of alkyne.

Determination of the Hammett Acidity of HF/Base Reagents

“…One of the most representative applications of such HF/base reagents in recent years is certainly the fluorofunctionalization of olefins and alkynes. This includes hydrofluorination (olefins, alkynes), halofluorination (olefins), difluorination (olefins), hetero­(S, Se, O, N)-fluorination (olefins), oxofluorination (alkynes), and other fluoro-cyclization/rearrangement . In many cases, a careful screening of HF/base reagents was necessary to improve the efficiency of these transformations.…”

An amorphous Lewis-acidic zirconium chlorofluoride as HF shuttle: C–F bond activation and formation

“…Note also that, in contrast, homogeneously catalysed reactions using Au( i ) and Pt( ii ) species as catalysts typically yield monofluoroalkenes. 40–46…”