The trifluoromethyl group (CF 3 ) is a key functionality in pharmaceutical and agrochemical development, greatly enhancing the efficacy and properties of resulting compounds. However, attaching the CF 3 group to heteroatoms such as sulfur, oxygen, and nitrogen poses challenges because of the lack of general synthetic methods and reliance on bespoke reagents. Here, we present a modular flow platform that streamlines the synthesis of heteroatom-CF 3 motifs. Our method uses readily available organic precursors in combination with cesium fluoride as the primary fluorine source, facilitating the rapid generation of N -trifluoromethyl(R) [NCF 3 (R)], SCF 3 (trifluoromethylthio), and OCF 3 (trifluoromethoxy) anions on demand without reliance on perfluoroalkyl precursor reagents. This strategy offers a more environmentally friendly synthesis of trifluoromethyl(heteroatom)–containing molecules, with the potential for scalability in manufacturing processes facilitated by flow technology.

中文翻译：

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三氟甲基杂原子阴离子的制备和使用的统一流程策略


三氟甲基 (CF 3 ) 是药物和农用化学品开发中的关键功能，可大大提高所得化合物的功效和特性。然而，由于缺乏通用的合成方法并且依赖于定制试剂，将CF 3 基团连接到硫、氧和氮等杂原子上提出了挑战。在这里，我们提出了一个模块化流程平台，可简化杂原子-CF 3 基序的合成。我们的方法使用现成的有机前体与氟化铯结合作为主要氟源，促进 N -三氟甲基(R) [NCF 3 (R)]、SCF 3 （三氟甲硫基）和 OCF 3 （三氟甲氧基）阴离子的快速生成按需提供，无需依赖全氟烷基前体试剂。该策略提供了一种更环保的含三氟甲基（杂原子）分子的合成方法，并具有流动技术促进的制造工艺可扩展性的潜力。