Since the first-raw metals have higher metal contamination limitations in pharmaceutical compounds and cheaper. Extensive global efforts have been devoted to the development of chiral catalysts with earth abundant, inexpensive, and nontoxic transitions metals. Nevertheless, non-precious metal catalysts in ketone hydrogenation are still far from satisfactory in terms of activity, selectivity and substrate scope. Recently, much effort has been devoted to the development of powerful chiral ligands for manganese-catalyzed enantioselective ketone hydrogenation. Based on this, in this work, we synthesized a series of three-toothed PNN ligands L1~L4 by introducing 8-aminoquinoline skeleton into facial chiral ferrocene, and applied these ligands to Mn-catalyzed asymmetric hydrogenation of a broad spectrum of ketones (49 examples) with high activities (1000 TON) and high enantioselectivities (up to 98% ee) using K₂CO₃ and EtOH as an industrially desirable base and solvent. To further demonstrate the utility of the developed Mn catalytic system, we applied it to the catalytic asymmetric hydrogenation of α-aminoketones (1-49, 1.46 g) with gram-scale and successfully obtained β-aminoalcohols (S)-2-49 in 1.25 g, 97% isolated yield and 81% ee within 24 h at 50 ℃ under hydrogen pressure of 4 MPa. Notably, the product (S)-2-49 is a key intermediate of (S)-phenylephrine. Although our attempts to get the crystal structure of Mn-L1 failed, the data of high resolution mass spectra and infrared spectra analysis strongly supported the hypothesized structure of Mn-L1, which contains two CO molecules.

Key words: arylamine NH, chiral PNN ligand, manganese complex, catalytic asymmetric hydrogenation, chiral alcohols