Efficient syntheses of mono‐, di‐, and heterodihalogenated derivatives of tyrosine N‐oxime methyl ester are reported. Monohalogenation with N‐bromosuccinimide (NBS), N‐chlorosuccinimide (NCS) or N‐iodosuccinimide (NIS) was optimized by addition of acid to suppress dihalogenation, affording bromo, chloro, and iodo derivatives in 71%, 50‐53%, and 78‐80% yields, respectively. Homodihalogenation utilized a two‐step, one‐flask process via a spirocyclic intermediate, yielding dibromo, dichloro, and diiodo analogues, respectively (75‐76%, 54‐56%, 79‐80%). This strategy was extended to synthesize heterodihalogenated bromochloro, bromoiodo, and chloroiodo derivatives from monohalogenated analogues (50‐77%). Key to this approach was the formation of an oxidized spirocyclic intermediate using excess N‐halosuccinimide, followed by Na₂S₂O₄ reduction. This method ensures complete conversion and simplifies purification. Nine halogenated building blocks were prepared. These methods provide practical access to versatile precursors for natural product synthesis and derivatization, offering potential for diverse synthetic applications including regioselective palladium‐catalyzed couplings.

中文翻译：

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关于酪氨酸 N-肟甲酯的卤化


报道了酪氨酸 N-肟甲酯的单卤化、二卤化和异二卤化衍生物的高效合成。通过添加酸来优化 N-溴琥珀酰亚胺 （NBS）、N-氯琥珀酰亚胺 （NCS） 或 N-碘琥珀酰亚胺 （NIS） 的单卤化反应以抑制二卤化，得到溴、氯和碘衍生物的产率分别为 71%、50-53% 和 78-80%。均型二卤化利用通过螺环中间体的两步单烧瓶工艺，分别产生二溴、二氯和二碘类似物（75-76%、54-56%、79-80%）。该策略扩展到从单卤代类似物合成异二卤代溴氯、溴碘和氯碘衍生物 （50-77%）。这种方法的关键是使用过量的 N-卤代琥珀酰亚胺形成氧化螺环中间体，然后还原 Na₂S₂O₄。这种方法可确保完全转化并简化纯化。制备了 9 个卤化结构块。这些方法为天然产物合成和衍生化提供了实用的通用前体，为多种合成应用提供了潜力，包括区域选择性钯催化偶联。