In:
Communications Chemistry, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2022-05-19)
Abstract:
Chiral γ-amino alcohols are the prevalent structural motifs and building blocks in pharmaceuticals and bioactive molecules. Enantioselective hydrogenation of β-amino ketones provides a straightforward and powerful tool for the synthesis of chiral γ-amino alcohols, but the asymmetric transformation is synthetically challenging. Here, a series of tridentate ferrocene-based phosphine ligands bearing modular and tunable unsymmetrical vicinal diamine scaffolds were designed, synthesized, and evaluated in the iridium-catalyzed asymmetric hydrogenation of β-amino ketones. The system was greatly effective to substrates with flexible structure and functionality, and diverse β-tertiary-amino ketones and β-secondary-amino ketones were hydrogenated smoothly. The excellent reactivities and enantioselectivities were achieved in the asymmetric delivery of various chiral γ-amino alcohols with up to 99% yields, 〉 99% ee values, and turnover number (TON) of 48,500. The gram-scale reactions with low catalyst loading showed the potential application in industrial synthesis of chiral drugs, such as ( S )-duloxetine, ( R )-fluoxetine, and ( R )-atomoxetine.
Type of Medium:
Online Resource
ISSN:
2399-3669
DOI:
10.1038/s42004-022-00678-4
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2929562-2
