Iridium-catalyzed enantioselective synthesis of chiral γ-amino alcohols and intermediates of (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine

Abstract

Enantioselective hydrogenation of β-amino ketones is a powerful tool to produce bioactive molecules, but their asymmetric transformation is synthetically challenging. Here, an iridium-catalysed system with tridentate ferrocene-based phosphine ligands bearing unsymmetrical vicinal diamine scaffolds is developed for the efficient asymmetric synthesis of diverse γtertiary-amino and γ-secondary-amino alcohols, including intermediates of (S)-duloxetine, (R)-fluoxetine and (R)-atomoxetine.