Zhang Li, Yan Jiyao, Ahmadli Dilgam, Wang Zikuan, Ritter Tobias
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany.
J Am Chem Soc. 2023 Sep 20;145(37):20182-20188. doi: 10.1021/jacs.3c07119. Epub 2023 Sep 11.
Direct C-H fluorination is an efficient strategy to construct aromatic C-F bonds, but the cleavage of specific C-H bonds in the presence of other functional groups and the high barrier of C-F bond formation make the transformation challenging. Progress for the electrophilic fluorination of arenes has been reported, but a similar transformation for electron-deficient azaarenes has remained elusive due to the high energy of the corresponding Wheland intermediates. Nucleophilic fluorination of electron-deficient azaarenes is difficult owing to the identity of the Meisenheimer intermediate after fluoride attack, from which fluoride elimination to regenerate the substrate is favored over hydride elimination to form the product. Herein, we report a new concept for C-H nucleophilic fluorination without the formation of azaarene Meisenheimer intermediates through a chain process with an asynchronous concerted F-e-H transfer. The concerted nucleophilic aromatic substitution strategy allows for the first successful nucleophilic oxidative fluorination of quinolines.
直接C-H氟化是构建芳族C-F键的有效策略，但在其他官能团存在下特定C-H键的裂解以及C-F键形成的高势垒使得这种转化具有挑战性。芳烃亲电氟化已有进展报道，但由于相应的Wheland中间体能量较高，缺电子氮杂芳烃的类似转化仍难以实现。缺电子氮杂芳烃的亲核氟化很困难，这是因为氟化物进攻后形成的迈森海默中间体的特性，从中消除氟化物以再生底物比消除氢化物以形成产物更有利。在此，我们报道了一种C-H亲核氟化的新概念，即通过具有异步协同F-e-H转移的链式过程，不形成氮杂芳烃迈森海默中间体。这种协同亲核芳香取代策略首次实现了喹啉的成功亲核氧化氟化。
