Chiral alcohols are important building blocks in the pharmaceutical and fine chemical industries. The enantioselective reduction of prochiral ketones catalyzed by transition metal complexes, especially asymmetric transfer hydrogenation (ATH) and asymmetric hydrogenation (AH), is one of the most efficient and practical methods for producing chiral alcohols. In both academic laboratories and industrial operations, catalysts based on noble metals such as ruthenium, rhodium, and iridium dominated the asymmetric reduction of ketones. However, the limited availability, high price, and toxicity of these critical metals demand their replacement with abundant, nonprecious, and biocommon metals. In this respect, the reactions catalyzed by first-row transition metals, which are more abundant and benign, have attracted more and more attention.As one of the most abundant metals on earth, iron is inexpensive, environmentally benign, and of low toxicity, and as such it is a fascinating alternative to the precious metals for catalysis and sustainable chemical manufacturing. However, iron catalysts have been undeveloped compared to other transition metals. Compared with the examples of iron-catalyzed asymmetric reduction, cobalt- and nickel-catalyzed ATH and AH of ketones are even seldom reported. In early 2004, we reported the first ATH of ketones with catalysts generated in situ from iron cluster complex and chiral PNNP ligand. Since then, we have devoted ourselves to the development of ATH and AH of ketones with iron, cobalt, and nickel catalysts containing novel chiral aminophosphine ligands. In our study, the iron catalyst containing chiral aminophosphine ligands, which are expected to control the stereochemistry at the metal atom, restrict the number of possible diastereoisomers, and effectively transfer chiral information, are successful catalysts for enantioselective reduction of ketones. Among these novel chiral aminophosphine ligands, 22-membered macrocycle P2N4 exhibited extraordinary enantioselectivities when combined with iron(0) cluster Fe3(CO)12. A broad scope of ketones including aromatic, heteroaromatic, and β-ketoesters can be reduced smoothly with excellent enantioselectivities (up to 99% ee) approaching or exceeding those achievable with the noble metal catalysts. Notably, the chiral iron-based catalyst proved to be highly efficient for both ATH as well as AH of various ketones. Until now, such “universal” catalyst is very rare. Preliminary studies suggest that the AH reaction most likely involved iron particles as the active catalytic species. These research results point to a new direction in developing viable effective nonprecious metal catalysts for asymmetric reduction and probably for other asymmetric catalytic reactions as well.

•Novel chiral bidentate P,N-containing ligands were synthesized and characterized.•Novel chiral Ru(II) complex was successfully prepared and characterized by X-ray diffraction studies.•ATH of various ketones catalyzed by chiral Ru(II) complex proceeded smoothly under mild conditions.Novel chiral bidentate P,N-containing ligands have been easily synthesized by Schiff-base condensation of o-(diphenylphosphino)benzaldehyde and modified chiral diamine, (R,R)-2-(2,5-dimethyl-pyrrol-1-yl)-cyclohexylamine, further reduction with NaBH4. The chiral ruthenium(II) complex could be successfully prepared from the reaction between chiral bidentate aminophosphine ligand and RuCl2(PPh3)3. The chiral bidentate P,N-containing ligands and ruthenium(II) complex were fully characterized by NMR, IR, HRMS and single-crystal X-ray diffraction studies. In the presence of KOH, the asymmetric transfer hydrogenation (ATH) of various ketones catalyzed by the chiral ruthenium(II) complex proceeded smoothly under mild conditions, affording corresponding chiral secondary alcohols with up to 99% conversion and up to 60% ee. Additive such as NH4I was found to be helpful to promoting the enantioselectivity.Novel chiral bidentate P,N-containing ligands and corresponding five-coordinated chiral ruthenium(II) complex have been successfully synthesized and characterized. The asymmetric transfer hydrogenation (ATH) of various ketones catalyzed by the chiral ruthenium(II) complex proceeded smoothly with up to 99% conversion and up to 60% ee.

A series of novel chiral C2-symmetric multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis(o-formylphenyl)phenylphosphane and easily available monoprotected (1R,2R)-diaminocyclohexane. The catalytic properties of these ligands were investigated in Ir-catalyzed asymmetric transfer hydrogenation of various aromatic ketones, giving the corresponding optical active alcohols with up to 98% conversion and good ee under mild reaction conditions.A series of novel chiral C2-symmetric multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis(o-formylphenyl)phenylphosphane and easily available monoprotected (1R,2R)-diaminocyclohexane. The catalytic properties of these ligands were investigated in Ir-catalyzed asymmetric transfer hydrogenation of various aromatic ketones, giving the corresponding optical active alcohols with up to 98% conversion and good ee under mild reaction conditions.

Using water as solvent, the oxidative kinetic resolution of a wide range of racemic secondary alcohols with a chiral PNNP/Ir catalyst was investigated. The catalytic reaction proceeded smoothly with excellent enantioselectivity (up to 97% ee) under mild conditions, providing an environmentally benign process to achieve optically active alcohols.

Novel chiral tetraaza ligands (R)-N, N′-bis[2-(piperidin-1-yl)benzylidene]propane-1, 2-diamine 6 and (S)-N-[2-(piperidin-1-yl)benzylidene]-3-{[2-(piperidin-1-yl)benzylidene]amino}-alanine sodium salt 7 have been synthesized and fully characterized by NMR, IR, MS and CD spectra. The catalytic property of the ligands was investigated in Ir-catalyzed enantioselective transfer hydrogenation of ketones. The corresponding optical active alcohols were obtained with high yields and moderate ees under mild reaction conditions.

Novel chiral PN4-type multidentate aminophosphine ligands have been successfully synthesized by Schiff-base condensation of bis(o-formylphenyl)phenylphosphane and various chiral amino-sulfonamides. Their structures were fully characterized by IR, EI-MS and NMR. The catalytic systems, prepared in situ from the multidentate ligands and iridium(I) complexes, showed high activity in asymmetric transfer hydrogenation of propiophenone in 2-propanol solution, leading to corresponding optical alcohol with up to 75% ee.