Remote Stereocontrol in the C6-Functionalization of Indoles via Synergistic Ion-Pair Catalysis

作者：Zhi‐Qiang Zhu, Han‐Peng Pan, Long Liang, Zhanhao Su, Ai‐Jun Ma, Jin‐Bao Peng, Hao Gao, Guodong Chen, Yongheng Wang, Xiang‐Zhi Zhang · 发表于：ACS Catalysis · 年份：2025 · DOI：10.1021/acscatal.5c00780 · 被引用次数：10 · 研究领域：Synthesis of Indole Derivatives、Asymmetric Synthesis and Catalysis、Catalytic C–H Functionalization Methods

Remote stereocontrol is a long-standing challenge in synthetic chemistry due to the diminishing influence of a catalyst’s chiral environment over extended distances. This limitation is particularly pronounced in the enantioselective C6-functionalization of indoles, a transformation of significant interest in pharmaceutical research and natural product synthesis. We herein present a visible-light-induced direct asymmetric C6-functionalization of indoles achieved through synergistic dual catalysis employing a chiral phosphoric acid and magnesium sulfate, which achieves precise remote stereocontrol. The reaction proceeds via an alkyne-carbonyl metathesis/1,6-addition cascade involving arylalkynes, benzoquinones, and indoles. This strategy facilitates the de novo synthesis of diverse enantioenriched indoles with acyclic all-carbon quaternary chiral centers at the C6 position, delivering high yields and enantioselectivities from simple and readily available starting materials. Moreover, the resulting products can be easily transformed into a range of structurally diverse molecules with all-carbon quaternary chiral centers, which are otherwise difficult to synthesize with a high enantiomeric purity. Several products also exhibit promising anticancer activities, highlighting their potential pharmaceutical relevance. Computational and experimental investigations reveal that magnesium sulfate significantly promotes the formation of the reaction precursor (binding free energy: −68.5 kc...