Selective 1,2‐Hydroarylation(Alkenylation) of gem ‐Difluoroalkenes to Access (−CF 2 H) Motifs

作者：Leroy Qi Hao Lin, Ángel Rentería‐Gómez, Robert T. Martin, Yingqi Zhang, Kelvin Zhi Wei Ong, Adam Parris, Osvaldo Gutiérrez, Ming Joo Koh · 发表于：Angewandte Chemie · 年份：2023 · DOI：10.1002/ange.202317935 · 被引用次数：2 · 研究领域：Fluorine in Organic Chemistry、Radical Photochemical Reactions、Catalytic C–H Functionalization Methods

Abstract An emerging class of C−C coupling transformations that furnish drug‐like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem ‐difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2‐selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl‐substituted carbon centers. In contrast to radical‐based pathways and reactions triggered by hydrometallation via a nickel‐hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel‐bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.