Zhang Ru Zhong, Liu Yang, Xu Cong, Wang Mang
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, College of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, 130024, China.
Nat Commun. 2025 May 28;16(1):4964. doi: 10.1038/s41467-025-60130-8.
N-CF amides are promising targets for pharmaceutical and agrochemistry. Unfortunately, there is a defluorination problem of N-CF amine starting materials when using common amide bond formation method. Recently, elegant alternative approaches emerged. However, none have used the well known amidyl radical chemistry to directly prepare N-CF amides. We describe here a convenient preparation of N-(N-CF imidoyloxy) pyridinium salts and their applications as efficient trifluoromethylamidyl radical precursors in photocatalytic trifluoromethylamidations of (hetero)arenes, alkenes, alkynes, silylenol ethers, and isocyanides. The rapid construction of diverse N-CF amides, particularly the synthesis of cyclic N-CF amides, demonstrates the uniqueness and flexibility of the method. This method is expected to provide a platform for directly synthesizing N-CF amides and to inspire the discovery of more redox molecular systems that can handle challenging trifluoromethylamidations.
N-碳氟酰胺是制药和农业化学领域颇具潜力的目标化合物。不幸的是，在使用常见的酰胺键形成方法时，N-碳氟胺起始原料存在脱氟问题。最近，出现了一些精妙的替代方法。然而，尚无方法利用广为人知的酰胺基自由基化学直接制备N-碳氟酰胺。我们在此描述了一种便捷的制备N-(N-碳氟亚氨酰氧基)吡啶盐的方法，以及它们作为高效三氟甲基酰胺基自由基前体在光催化（杂）芳烃、烯烃、炔烃、硅烯醇醚和异腈的三氟甲基酰胺化反应中的应用。多样的N-碳氟酰胺的快速构建，尤其是环状N-碳氟酰胺的合成，证明了该方法的独特性和灵活性。预计该方法将为直接合成N-碳氟酰胺提供一个平台，并激发发现更多能够处理具有挑战性的三氟甲基酰胺化反应的氧化还原分子体系。
