Selective 1,2‐Hydroarylation(Alkenylation) of gem‐Difluoroalkenes to Access (−CF2H) Motifs

作者：Leroy Qi Hao Lin, Ángel Rentería‐Gómez, Robert T. Martin, Yingqi Zhang, Kelvin Zhi Wei Ong, Adam B. Parris, Osvaldo Gutiérrez, Ming Joo Koh · 发表于：Angewandte Chemie International Edition · 年份：2023 · DOI：10.1002/anie.202317935 · 被引用次数：24 · 研究领域：Fluorine in Organic Chemistry、Inorganic Fluorides and Related Compounds、Web Data Mining and Analysis

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.