Amine-Borane-Promoted Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of β-Chloro Ketones.

We report a rhodium-catalyzed asymmetric transfer hydrogenation of β-chloro ketones promoted by amine-boranes. A broad range of substrates was reduced in up to 99% yield and >99% ee, with gram-scale reactions completed within 1 h. The resulting 3-chloroalkanols serve as versatile intermediates for the synthesis of pharmaceuticals such as (S)-Nisoxetine, (S)-Fluoxetine, (S)-Tomoxetine, (S)-Duloxetine, (S)-Dapoxetine, and Ezetimibe analogues. DFT calculations reveal that C-H···π interactions and hydrogen bonding control stereoselectivity, and the effect of different amine-boranes on enantioselectivity was rationalized, providing guidance for broader application in asymmetric transfer hydrogenation.