Synthesis of Sterically Hindered f-Amphbinol Ligands and Application in Iridium-Catalyzed Asymmetric Hydrogenation of Various Ketones

We have synthesized a series of sterically hindered ligands f-Amphbinol L1-L3, which were successfully applied in the asymmetric hydrogenation of various ketones with excellent results (up to 63 examples, 95 → 99% yields, 90 → 99% ee, >20:1 dr). Ligand screening experiments demonstrated that the enantioselectivity of hydrogenation increases with the increase in the steric hindrance of substituents on P-aryl rings of the ligand. Besides, the key intermediates for API Ladostigil were successfully synthesized with this catalyst system, which hinted at the potential applications.