Research On The Synthesis Of α-Fluoro-α,β-Unsaturated Carbonyl Compounds

Fluorine-containing compounds have been widely used in pharmaceuticals, pesticides, paints and materials because of their unique biological activity and physicochemical properties. Fluorine-containing organic compounds, especially α-fluoro-α,β-unsaturated carbonyl compounds, related to a variety of important drugs with outstanding efficacy and biological activity, have been selling in the clinical market for many years. Thanks to the introduction of fluorine atom to a-position of α,β-unsaturated carbonyl compounds, the physicochemical properties and biological activety of the molecules can be greatly improved. Thus, it is significant to develop a simple and practical method for the synthesis of α-fluoro-α,β-unsaturated carbonyl compounds.In this paper, α-fluoro-α,β-unsaturated compounds was synthesized by direct C-H fluorination of α,β-unsaturated compounds. Selectfluor was used as the F-source, which introduces the flourine atom into α,β-unsaturated carbonyl compounds such as chalcones, cinnamates, coumarins and quinolinones to afford the α-fluorinated products. The optimum reaction conditions are as follows:the equivalent of Selectfluor was 2-2.6, the temperature was 70℃-85℃, the reaction time was 12 h-36 h, the solvent was a mixture of MeCN and DMF, MeCN:DMF=9:1, and the yield was up to 65%.40 kinds of α-fluoro-α,β-unsaturated carbonyl compounds were synthesized and 8 of them were new compounds. The products were characterized by 1H NMR,13C NMR,19F NMR, HRMS, and Single-crystal X-ray Diffraction.Direct C-H fluorination of α,β-unsaturated compounds was the most efficient approach to form C-F bond since it obviated the need of pre-functionalization of α,β-unsaturated compounds, and the reaction could be carried out under mild conditions without catalyst. Besides, the yields were high and it was suitable for a wide range of substrates.