Synthesis of gem-difluoro derivatives of natural products by the reaction of ketones with diethylaminosulphur trifluoride

Abstract

The preparation of gem-difluoro compounds, including 12,12-difluoro-octadecanoic acid, 7,7-difluorohexadecanoic acid, ent-7,7-difluorokauran-19-ol (8), and 2,2,7-trifluoro-10β-methoxycarbonyl-1β,8-dimethylgibban1α,4aα-carbolactones (18) and (19), is described. Each synthesis involved fluorination of the appropriate ketone with diethylaminosulphur trifluoride, and the reaction conditions required varied from 6 h at 0 °C for the gibberellin derivatives (14) and (15) to 7 d at 115 °C for methyl 1 2-oxo-octadecanoate. gem-Difluorides are usually stable to alkali, but in the fluorogibberellins (18) and (19) the 2,2-difluoro-groups were readily hydrolysed to the correponding 2-ketones.