Organofluorine compounds have greatly benefited the pharmaceutical, agrochemical, and materials sectors. However, they are plagued by concerns associated with PFAS. Additionally, the widespread use of the trifluoromethyl group is facing imminent regulatory scrutiny. Defluorinative functionalization, which converts the trifluoromethyl to the difluoromethyl motifs, represents the most efficient synthetic strategy. However, general methods for robust C(sp3)–F bond transformations remain elusive due to challenges in selectivity and functional group tolerance. Here, we present a method for C(sp3)–F bond defluorinative functionalization of the trifluoromethyl group via difluoromethyl anion in flow. This new approach tames the reactive difluoromethyl anion, enabling diverse functional group transformations. Our methodology offers a versatile platform for drug and agrochemical discovery, overcoming the limitations associated with fluorinated motifs.

中文翻译：

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二氟甲基阴离子化学主导的脱氟功能化方法

有机氟化合物使制药、农化和材料领域受益匪浅。然而，他们却受到与 PFAS 相关的担忧的困扰。此外，三氟甲基的广泛使用正面临迫在眉睫的监管审查。脱氟官能化将三氟甲基转化为二氟甲基基序，代表了最有效的合成策略。然而，由于选择性和官能团耐受性方面的挑战，稳健的 C(sp3)-F 键转化的通用方法仍然难以捉摸。在这里，我们提出了一种通过流动中的二氟甲基阴离子对三氟甲基进行 C(sp3)-F 键脱氟官能化的方法。这种新方法驯服了反应性二氟甲基阴离子，实现了多种官能团的转化。我们的方法为药物和农用化学品的发现提供了一个多功能平台，克服了与氟化基序相关的限制。