Matsuo Bianca, Majhi Jadab, Granados Albert, Sharique Mohammed, Martin Robert T, Gutierrez Osvaldo, Molander Gary A
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania 231 South 34th Street Philadelphia Pennsylvania 19104-6323 USA
Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive College Park Maryland 20742 USA.
Chem Sci. 2023 Feb 9;14(9):2379-2385. doi: 10.1039/d2sc06179a. eCollection 2023 Mar 1.
The development of strategies for single and selective C-F bond activation represents an important avenue to overcome limitations in the synthesis of valuable fluorine-containing compounds. The synthetic and medicinal research communities would benefit from new routes that access such relevant molecules in a simple manner. Herein we disclose a straightforward and mechanistically distinct pathway to generate -difluoromethyl radicals and their installation onto -arylmethacrylamides for the preparation of valuable difluorinated oxindole derivatives. To achieve operational simplicity, the use of a readily available benzenethiol as a photocatalyst under open-to-air conditions was developed, demonstrating the facile multigram preparation of the targeted fluorinated molecules. Additionally, dispersion-corrected density functional theory (DFT) and empirical investigations provide a new basis to support the proposed reaction pathway, indicating that arene thiolate is an efficient organophotocatalyst for this transformation.
单选择性碳-氟键活化策略的发展是克服合成有价值含氟化合物局限性的重要途径。合成和药物研究领域将受益于能以简单方式获取此类相关分子的新路线。在此，我们公开了一条直接且机理独特的途径，用于生成二氟甲基自由基并将其引入芳基甲基丙烯酰胺，以制备有价值的二氟代氧化吲哚衍生物。为实现操作简便性，开发了在空气条件下使用易于获得的苯硫酚作为光催化剂的方法，展示了目标氟化分子的简便多克级制备。此外，色散校正密度泛函理论（DFT）和实证研究为支持所提出的反应途径提供了新依据，表明芳基硫醇盐是这种转化的有效有机光催化剂。
