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

• Published in: ACS catalysis 2018-07, Vol.8 (7), p.5947-5951
• Main Authors: O’Connor, Thomas J, Toste, F. Dean
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.8b01341

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.