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

The gold(I)-catalyzed, stereoselective hydro fluorination of electron-deficient alkynes with triethylamine trihydrogen fluoride (Et3N-3HF) is described. Fluorinated alpha,beta-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 beta-alkyl, beta-fluoro Michael acceptors from alkynes. Additionally, the described work expands access to beta-aryl, beta-fluoro Michael acceptors to the synthesis of beta-fluoro-alpha,beta-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.