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.

Chiral molecules, such as alcohols, are vital for the manufacturing of fine chemicals, pharmaceuticals, agrochemicals, fragrances, and novel materials. These molecules need to be produced in high yield and high optical purity and preferentially catalytically. Among all the asymmetric catalytic reactions, asymmetric hydrogenation with H2 (AH) is the most widely used in the industry. With few exceptions, these AH processes use catalysts based on the three critical metals, rhodium, ruthenium, and iridium. Herein we describe a simple, industrially viable iron catalyst that allows for the AH of ketones, a process currently dominated by ruthenium and rhodium catalysts. By combining a chiral, 22-membered macrocyclic ligand with the cheap, readily available Fe3(CO)12, a wide variety of ketones have been hydrogenated under 50 bar H2 at 45–65 °C, affording highly valuable chiral alcohols with enantioselectivities approaching or surpassing those obtained with the noble metal catalysts. In contrast to AH by most noble metal catalysts, the iron-catalyzed hydrogenation appears to be heterogeneous.

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.

The new polydentate mixed-N, P, O chiral ligands have been synthesized by the condensation of bis(o-formylphenyl)-phenylphosphane and R-phenylglycinol in CHCl3, and fully characterized by IR, NMR and EIMS spectra. These ligands were employed with a simple Ni complex Ni(PPhs)2Cl2in situ as catalytic systems for asymmetric transfer hydrogenation of ketones, and the corresponding optical alcohols were obtained with up to 84% ee under mild conditions.

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.

The chiral diamino-bis(bithiophene) ligands were firstly employed in the iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. The new catalyst systems, generated in situ from chiral diamino-bis(bithiophene) ligands and IrCl(CO)(PPh3)2 in iPrOH, gave the corresponding optically active secondary alcohols with high yield and fair to good enantioselectivities (up to 90% ee). The chiral Ir(I)/diamino-bis(bithiophene) complexes were also synthesized and characterized. The XPS spectra showed that the potentially multidentate ligands coordinated to the Ir atom through the nitrogen atoms, while the thiophene pendants did not participate in coordination to the Ir atom.The chiral diamino-bis(bithiophene) ligands were employed in the iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones firstly, giving the corresponding optically secondary alcohols with high yield and up to 90% ee. The coordination environment of the diamino-thiophene ligands on the Ir atom was also investigated.

Novel chiral tetraaza ligands, N1,N2-bis(2-(piperidin-1-yl)benzylidene)cyclohexane-1,2-diamine 1 and N1,N2-bis(2-(piperidin-1-yl)benzyl)cyclohexane-1,2-diamine 2, have been synthesized and fully characterized by analytical and spectroscopic methods. The structure of (R,R)-1 has been established by X-ray crystallography. Asymmetric transfer hydrogenation of aromatic ketones with the catalysts prepared in situ from [IrHCl2(COD)]2 and the chiral tetraaza ligands in 2-propanol gave the corresponding optically active secondary alcohols in high conversions and good ees (up to 91%) under mild reaction conditions.(1R,2R)-N1,N2-Bis(2-(piperidin-1-yl)benzylidene)cyclohexane-1,2-diamineC30H40N4[α]D20=+85.5 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)(1R,2R)-N1,N2-Bis(2-(piperidin-1-yl)benzyl)cyclohexane-1,2-diamineC30H44N4[α]D20=-55.4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

New efficient catalyst systems, coupled with IrCl(COD)PPh3 and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.(1R,2R)-N1,N2-Bis(thiophen-2-ylmethyl)cyclohexane-1,2-diamineC16H22N2S2Mp 57 °C[α]D20=-102.0 (c 0.5, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (1R, 2R)

The interaction of [Rh(COD)Cl]2 with two equivalents of (S)-N,N′-bis[o-(diphenylphosphino)benzylidene]propane-1,2-diamine [(S)-1] or (S)-N,N′-bis[o-(diphenylphosphino)benzyl]propane-1,2-diamine [(S)-2] in benzene/methanol mixture and then precipitation by the addition of a solution of NH4PF6 in water afforded cationic rhodium(I) complexes [Rh(S)-MeP2N2][PF6] and [Rh(S)-MeP2(NH)2][PF6] in good yield, respectively. Complexes [Rh(R,R)-C6P2N2][PF6] and [Rh(R,R)-C6P2(NH)2][PF6] were also prepared by an analogous manner. All these rhodium complexes have been characterized by analytical and spectroscopic methods and their asymmetric catalytic properties for enantioselective transfer hydrogenation of acetophenone have been tested. [Rh(R,R)-C6P2(NH)2][PF6] was used as an excellent catalyst precursor for enantioselective transfer reduction of acetophenone in 2-propanol, leading to 2-phenylathanol in 97% yield and in 91% ee after 7 h at 83°C.