Heterocycle skeletal editing has recently emerged as a powerful tactic for achieving heterocycle-to-heterocycle transmutation without the need for multistep de novo heterocycle synthesis. However, the enantioselective skeletal editing of heteroarenes through single-atom logic remains challenging. Here we report the enantiodivergent dearomative skeletal editing of indoles and pyrroles via an asymmetric carbon-atom insertion, using trifluoromethyl N-triftosylhydrazones as carbene precursors. This strategy provides a straightforward methodology to access enantiomerically enriched six-membered N-heterocycles containing a trifluoromethylated quaternary stereocentre from planar N-heteroarenes. The synthetic utility of this enantiodivergent methodology was demonstrated by a broad evaluation of reaction scope, product derivatization and concise syntheses of drug analogues. Mechanistic studies reveal that the excellent asymmetric induction arises from the initial cyclopropanation step. The asymmetric single-atom insertion strategy is expected to have a broad impact on the field of single-atom skeletal editing and catalytic asymmetric dearomatization of aromatic compounds.

杂环骨架编辑最近成为一种强大的策略，无需多步从头杂环合成即可实现杂环到杂环嬗变。然而，通过单原子逻辑对异芳烃进行对映选择性骨架编辑仍然具有挑战性。在这里，我们报道了使用三氟甲基 N-三酰腙作为卡宾前体，通过不对称碳原子插入对吲哚和吡咯的对映体去反作用骨架编辑。该策略提供了一种简单的方法来访问来自平面 N-杂芳烃的对映体富集的六元 N-杂环，其中包含三氟甲基化四元立体中心。通过对反应范围、产物衍生化和药物类似物的简明合成的广泛评估，证明了这种对映体差异方法的合成效用。机理研究表明，出色的不对称诱导源于初始环丙烷化步骤。不对称单原子插入策略预计将对芳香族化合物的单原子骨架编辑和催化不对称脱芳烃领域产生广泛影响。