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

Abstract

The addition of excess alkali metal to Noyori-type catalysts (HM-NH) generates anionic species (HM-NM’), which significantly enhances both the reaction rate and turnover number (TON) in asymmetric hydrogenation. However, such anionic catalysts have been largely confined to the construction of central chirality, with few reports on application to axial chirality. Herein, we report a highly efficient anionic iridium catalyst (HIr-NCs) based on a newly tridentate ligand framework (Huaphos), which enables the asymmetric hydrogenation of N-aryl indole ketones (and aldehydes) via 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.