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Bulky alkali metal cations enabled highly efficient iridium-catalyzed asymmetric hydrogenation for C–N axial chirality <i>via</i> dynamic kinetic resolution

Xianghua Zhao, Xinyu Chen, Linxian Fan, Yulong Jiang, Yirui Chen, Dingguo Song, Fei Ling, Junyuan Hu, Weihui Zhong

2025Chemical Science8 citationsDOIOpen Access PDF

Abstract

dynamic kinetic resolution under mild conditions, allowing for the construction of axial chirality with excellent stereocontrol (up to >99% ee and >99 : 1 dr). DFT studies indicate that strong electrostatic interaction between the bulky cesium cation and the oxygen atom of the substrate dramatically reduces the activation barrier, resulting in a substantially accelerated reaction rate for the anionic Ir catalyst (HIr-NCs) compared to the neutral Ir/Huaphos system (HIr-NH). In the presence of anionic Ir catalyst, this protocol can be scaled up to gram quantities under an exceptionally low catalyst loading (S/C = 40 000), and the resulting hydrogenation product can be further transformed into novel chiral ligands that show promise in asymmetric catalysis.

Topics & Concepts

CatalysisIridiumKinetic resolutionAsymmetric hydrogenationChirality (physics)ChemistryAlkali metalSubstrate (aquarium)Enantioselective synthesisLigand (biochemistry)PhotochemistryMetalAxial chiralityCaesiumInorganic chemistryNitrogen atomAtom (system on chip)Catalytic cycleReaction rateMaterials sciencePhysical chemistryCombinatorial chemistryChiral ligandComputational chemistryReaction intermediateEnantiomeric excessReaction mechanismAsymmetric Hydrogenation and CatalysisAxial and Atropisomeric Chirality SynthesisAsymmetric Synthesis and Catalysis
Bulky alkali metal cations enabled highly efficient iridium-catalyzed asymmetric hydrogenation for C–N axial chirality <i>via</i> dynamic kinetic resolution | Litcius