Discovery and development of ferrocene-based tetradentate ligands for Ir-catalysed asymmetric hydrogenation of ketone

Abstract

The development of highly active and enantioselective ligands and catalysts for the asymmetric hydrogenation of ketone has been the goal of synthetic chemists for more than fifty years. Herein, a series of ferrocene-based tetradentate ligands were developed and applied in Ir-catalysed asymmetric hydrogenation of ketone. The hydrolytic ring-opening of the oxazoline moiety of ligand f-amphox leads to the accidental discovery of a highly efficient and enantioselective tetradentate ligand f-phamidol which showed extraordinarily high reactivity and enantioselectivity (up to 99% yield, up to >99% ee and up to 1,000,000 TON). In addition, two types of other tetradentate ligands f-phamida and f-phamide were also synthesized and evaluated.

Keywords

• Asymmetric hydrogenation of ketones
• Ferrocene-based ligands
• Iridium-catalysed
• Tetradentate ligands