Nucleophilic aromatic substitution (S_NAr) is routinely used to install ¹⁹F^– and ¹⁸F^– in aromatic molecules, but is typically limited to electron-deficient arenes due to kinetic barriers associated with C–F bond formation. Here we demonstrate that a polarity-reversed photoredox-catalysed arene deoxyfluorination that operates via cation-radical-accelerated S_NAr enables the fluorination of electron-rich arenes with ¹⁹F^– and ¹⁸F^– under mild conditions, and thus complements the traditional arene polarity requirements necessary for S_NAr-based fluorination. The utility of our radiofluorination strategy is highlighted by short reaction times, compatibility with multiple nucleofuges and high radiofluorination yields, especially that of an important cancer positron emission tomography agent [¹⁸F]5-fluorouracil. Taken together, our fluorination approach enables the development of fluorinated and radiofluorinated compounds that can be difficult to access by classical S_NAr strategies, with the potential for use in the synthesis and discovery of positron emission tomography radiopharmaceuticals.

亲核芳族取代 (S _N Ar) 通常用于在芳族分子中安装¹⁹ F ^-和¹⁸ F ^- ，但由于与 C-F 键形成相关的动力学势垒，通常仅限于缺电子芳烃。在这里，我们证明了通过阳离子自由基加速 S _N Ar 进行的极性反转光氧化还原催化芳烃脱氧氟化能够在温和条件下用^{19 F}和^{18 F}氟化富电子芳烃，从而补充了传统的芳烃S _N Ar 基氟化所需的极性要求。我们的放射性氟化策略的实用性突出在于反应时间短、与多种离核剂兼容和高放射性氟化产率，尤其是重要的癌症正电子发射断层扫描剂[ ¹⁸ F]5-氟尿嘧啶。总而言之，我们的氟化方法能够开发传统 S _N Ar 策略难以获得的氟化和放射性氟化化合物，并具有用于合成和发现正电子发射断层扫描放射性药物的潜力。