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Visible-Light-Driven Cobalt-Catalyzed Assembly of Indole-Alcohols Bearing Concurrent Axial and Central Chiralities via Dynamic Kinetic Resolution

Yunliang Guo, Ximin Liu, Lan Hu, Jiuli Xia, Yujie Li, Lihan Zhu, Jiaqiong Sun, Guangfan Zheng, Qian Zhang

2025ACS Catalysis19 citationsDOI

Abstract

High Resolution Image Download MS PowerPoint Slide N -Arylindoles featuring N–C axially chiral architectures constitute privileged scaffolds prevalent in pharmacologically active natural products and asymmetric catalysis. Despite significance, current synthetic strategies predominantly focus on constructing single stereogenic elements; simultaneous installation of both axial chirality (N–C axis) and central chirality within indole frameworks presents an emerging area. Herein, we disclose that a visible-light-driven cobalt-catalyzed reductive coupling of N -arylindole aldehydes with aryl iodides via dynamic kinetic resolution process enables direct assembly of indole-alcohols bearing both C–N axial and central chiralities with up to 99% ee and >20:1 dr. Mechanistic investigations integrated with DFT calculations reveal a critical axially chiral ketyl radical intermediate, which undergoes cobalt–OH coordination-facilitated S H 2-type arylation, delivering enantio-enriched indole-alcohols.

Topics & Concepts

Axial chiralityKinetic resolutionAxial symmetryChirality (physics)StereocenterArylKetylMaterials scienceChemistryIndole testCoupling (piping)CatalysisBearing (navigation)Chemical physicsStereochemistryComputational chemistryKinetic energyResolution (logic)NanotechnologyCombinatorial chemistryCoupling reactionMolecular physicsAxial and Atropisomeric Chirality SynthesisMolecular spectroscopy and chiralityCatalytic C–H Functionalization Methods