Multicomponent Dearomative Difluoroalkylation of Isoquinolines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of gem-Difluorinated Heterocycles

Abstract

A multicomponent dearomative difluoroalkylation of isoquinolines has been developed with difluorinated silyl enol ethers serving as poor nucleophiles without an additional transition-metal or organic catalyst. The sequential oxidative rearomatization under different alkaline conditions provides a controllable formal C−H difluoroalkylation and difluoromethylation method for isoquinolines without peroxide or metal oxidant. A series of isoquinolines including a pharmaceutical, phenanthridine, quinolines, and difluorinated silyl enol ethers were suitable substrates to construct gem-difluorinated heterocycles. The inexpensive starting materials, mild reaction conditions, and simple operation also show practical and environmentally benign advantages.

Synthesis of Fluoro 3(2H)-Furanones via a TFA-Catalyzed Dehydrofluorinative Cyclization of 2,2-Difluoro-3-hydroxy-1,4-diketones

“…Because the preparation of Selectfluor or NFSI requires fluorine gas, which is not practical largely for safety reasons, the development of readily available, efficient, and cost-effective fluorinated substrates to construct fluoro 3­(2 H )-furanones is in high demand. Recently, our group pays considerable attention for the construction of difluorinated compounds, and we are excited to find that through a cascade dehydrofluorinative process, the difluorinated compounds can be transformed to fluorinated heterocycles efficiently under mild conditions . Hence, we developed this distinctive TFA-catalyzed dehydrofluorinative cyclization of 2,2-difluoro-3-hydroxy-1,4-diketones previously reported by our group to provide an efficient method for fluoro 3­(2 H )-furanones (Scheme d).…”