UC Berkeley

The gold(I)-catalyzed, stereoselective hydrofluorination of electron-deficient alkynes with triethylamine trihydrogen fluoride (Et₃N·3HF) is described. Fluorinated α,β-unsaturated aldehydes, amides, esters, ketones, and nitriles were isolated in moderate to good yields as single diastereomers. In all but four cases, the (Z)-vinyl fluorides were initially formed in ≥97% diastereoselectivity. This work constitutes the first catalytic example of the diastereoselective preparation of a variety of β-alkyl, β-fluoro Michael acceptors from alkynes. Additionally, the described work expands access to β-aryl, β-fluoro Michael acceptors to the synthesis of β-fluoro-α,β-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.