Palladium/Lipase-Catalyzed Asymmetric Reductive Acylation of Ketoximes

Significance

The one-pot asymmetric synthesis of optically active amides 3a-h from ketoximes 1a-h with aluminum hydroxide supported palladium catalyst [Pd/AlO(OH)] and lipase (Novozym-435) is described. Thus, the reaction of ketoximes 1a-h (0.30 mmol) with 2 was carried out in the presence of Pd/AlO(OH), Novozym-435 (9 mg), and 4 A MS (100 mg) in toluene under H₂ to give the corresponding amides 3a-h with high enan­tioselectivity (83-92% yield, 93-98% ee). Amide 3a (0.26 mmol, 98% ee) was reduced by LiAlH₄ in THF to afford the secondary amine 4 in 97% yield with 98% ee.