Ir-f-Amphbinol-Catalyzed Asymmetric Hydrogenation of N-Protected α-Amino Ketones Followed by Deprotection for Preparation of β-Primary Amino Alcohols.

Abstract

We have successfully developed a highly efficient Ir-f-Amphbinol-catalyzed asymmetric hydrogenation for various α-amino ketones with different substituents on the -NH2. A series of α-amino ketones containing easily introduced and removed groups (Boc-, Ac-, Bz-, Ts-) were successfully converted into the corresponding chiral alcohols with 96∼>99% yields, 95:5-97:3 dr, and 90∼>99% ee. The versatility of this method is demonstrated through the derivatization of products, including deprotection to get the key intermediates of six pharmaceuticals. Noteworthily, we have innovatively applied the chiral β-primary amino alcohol 3-1 prepared by the abovementioned method to the efficient synthesis of dominant chiral tridentate PNO-type ligands L1-L2 and applied them to the efficient iridium-catalyzed asymmetric hydrogenation of various ketones. Based on the literature reports and our experimental results, we further proposed a possible ONa/MH instead of NNa/MH bifunctional mechanism.