Single-atom skeletal editing is an increasingly powerful tool for scaffold hopping-based drug discovery. However, the insertion of a functionalized carbon atom into heteroarenes remains rare, especially when performed in complex chemical settings. Despite more than a century of research, Ciamician-Dennstedt (C-D) rearrangement remains limited to halocarbene precursors. Herein, we report a general methodology for the Ciamician-Dennstedt reaction using α-halogen-free carbenes generated in situ from N-triftosylhydrazones. This one-pot, two-step protocol enables the insertion of various carbenes, including those previously unexplored in C-D skeletal editing chemistry, into indoles/pyrroles scaffolds to access 3-functionalized quinolines/pyridines. Mechanistic studies reveal a pathway involving the intermediacy of a 1,4-dihydroquinoline intermediate, which could undergo oxidative aromatization or defluorinative aromatization to form different carbon-atom insertion products.

单原子骨骼编辑是一种越来越强大的基于支架跳跃的药物发现工具。然而，将官能化碳原子插入杂芳烃中的情况仍然很少见，尤其是在复杂的化学环境中进行时。尽管经过一个多世纪的研究，Ciamician-Dennstedt （C-D） 重排仍然局限于卤代卡宾前体。在此，我们报告了使用 N-三三基腙原位生成的无 α 卤素卡宾的 Ciamician-Dennstedt 反应的一般方法。这种一锅两步方案能够将各种卡宾（包括以前在 C-D 骨骼编辑化学中未探索的卡宾）插入吲哚/吡咯支架中，以获得 3 官能化的喹啉/吡啶。机理研究揭示了一种涉及 1,4-二氢喹啉中间体中间体的途径，该中间体可以经历氧化芳构化或脱氟芳构化以形成不同的碳原子插入产物。