东北师范大学毕锡和团队报道了吲哚和吡咯的非对称脱芳香单原子骨架编辑。相关研究成果发表在2024年11月28日出版的《自然—化学》。

最近，杂环骨架编辑成为了一种强大的策略，可以在不需要多步从头合成杂环的情况下，实现杂环到杂环的转变。然而，通过单原子逻辑，对杂芳烃进行对映选择性骨架编辑仍然具有挑战性。

该文中，研究人员报告了通过不对称碳原子插入，使用三氟甲基N-三氟甲苯磺酰腙作为卡宾前体，对吲哚和吡咯进行对映异构脱芳烃骨架编辑。该策略提供了一种直接的方法，从平面N-杂芳烃中获得含有三氟甲基化季立体中心的，对映体富集的六元N-杂环。

研究人员通过对反应范围、产物衍生化和药物类似物简洁合成的广泛评估，证明了这种对映体富集方法的合成实用性。机理研究表明，优异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有望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。

附：英文原文

Title: Asymmetric dearomative single-atom skeletal editing of indoles and pyrroles

Author: Zhang, Xiaolong, Song, Qingmin, Liu, Shaopeng, Sivaguru, Paramasivam, Liu, Zhaohong, Yang, Yong, Ning, Yongyue, Anderson, Edward A., de Ruiter, Graham, Bi, Xihe

Issue&Volume: 2024-11-28

Abstract: 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.

DOI: 10.1038/s41557-024-01680-0

Source: https://www.nature.com/articles/s41557-024-01680-0