Multicomponent Dearomative Difluoroalkylation of Isoquinolines with Difluorinated Silyl Enol Ethers: Divergent Synthesis of <i>gem</i>-Difluorinated Heterocycles
Miaomiao Mu, Saimei Liu, Yuru He, Jǐnjīng Xǔ, Haijian Wu, Qiyuan Du, Manman Sun, Jianguo Yang, Zhiming Wang
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.