Gold-Catalyzed Hydrofluorination of Electron-Deficient Alkynes: Stereoselective Synthesis of β-Fluoro Michael Acceptors

The gold(I)-catalyzed, stereoselective hydrofluorination of electron-deficient alkynes with triethylamine trihydrogen fluoride (Et₃N·3HF) is described. Fluorinated <i>α,β</i>-unsaturated aldehydes, amides, esters, ketones, and nitriles were isolated in moderate to good yields as single diastereomers. In all but four cases, the (<i>Z</i>)-vinyl fluorides were initially formed in ≥97% diastereoselectivity. This work constitutes the first catalytic example of the diastereoselective preparation of a variety of <i>β</i>-alkyl, <i>β</i>-fluoro Michael acceptors from alkynes. Additionally, the described work expands access to <i>β</i>-aryl, <i>β</i>-fluoro Michael acceptors to the synthesis of <i>β</i>-fluoro-<i>α,β</i>-unsaturated amides and nitriles. The monofluoroalkenes formed through this strategy were readily transformed into other fluorine-containing compounds, and the developed method was applied to the synthesis of a fluorinated analogue of Exoderil, a topical antimycotic.