Asymmetric Hydrogenation Of Ketones Research Articles

Asymmetric hydrogenation of trifluoromethyl ketones: application in the synthesis of Odanacatib and LX-1031

The asymmetric hydrogenation of trifluoromethyl ketones via iridium catalysis to access chiral secondary 2,2,2-trifluoroethanols is presented. The key intermediates of Odanacatib and LX1301 were prepared with high yields and enantioselectivities.

Effectiveness and Mechanism of the Ene(amido) Group in Activating Iron for the Catalytic Asymmetric Transfer Hydrogenation of Ketones

π-interacting ligands of the diphosphino amido-ene(amido) type are effective in activating iron to resemble the properties of precious metals in the catalytic asymmetric transfer hydrogenation of k...

Arene‐Immobilized Ru(II)/TsDPEN Complexes: Synthesis and Applications to the Asymmetric Transfer Hydrogenation of Ketones

AbstractThe Noyori‐Ikariya (arene)Ru(II)/TsDPEN precatalyst has been anchored to amorphous silica and DAVISIL through the η6‐coordinated arene ligand via a straightforward synthesis and the derived systems, (arene)Ru(II)/TsDPEN@silica and (arene)Ru(II)/TsDPEN@DAVISIL, form highly efficient catalysts for the asymmetric transfer hydrogenation of a range of electron‐rich and electron‐poor aromatic ketones, giving good conversion and excellent ee's under mild reaction conditions. Moreover, catalyst generated in situ immediately prior to addition of substrate and hydrogen donor, by reaction of silica‐supported [(arene)RuCl2]2 with (S,S)‐TsDPEN, was as efficient as that generated from its preformed counterpart [(arene)Ru{(S,S)‐TsDPEN}Cl]@silica. Gratifyingly, the initial TOFs (up to 1085 h−1) and ee's (96–97 %) obtained with these catalysts either rivalled or outperformed those previously reported for catalysts supported by either silica or polymer immobilized through one of the nitrogen atoms of TsDPEN. While the high ee's were also maintained during recycle studies, the conversion dropped steadily over the first three runs due to gradual leaching of the ruthenium.

Asymmetric transfer hydrogenation of unsaturated ketones; factors influencing 1,4- vs 1,2- regio- and enantioselectivity, and alkene vs alkyne directing effects

A detailed study has been completed on the asymmetric transfer hydrogenation (ATH) of a series of enones using Ru(II) catalysts. Electron-rich rings adjacent to the CO group reduce the level of CO reduction compared to CC. The ATH reaction can readily discriminate between double and triple bonds adjacent to ketones, reducing the double bond but leaving a triple bond intact in the major product.

C1-Symmetric PNP Ligands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones: Reaction Scope and Enantioinduction Model

A family of ferrocene-based chiral PNP ligands is reported. These tridentate ligands were successfully applied in Mn-catalyzed asymmetric hydrogenation of ketones, giving high enantioselectivities ...

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral PxNy-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)5] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP2N4 (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.

A Cobalt(II) Complex Bearing the Amine(imine)diphosphine PN(H)NP Ligand for Asymmetric Transfer Hydrogenation of Ketones

Novel chiral cobalt complex a containing amine(imine)diphosphine PN(H)NP ligand and complex b containing bis(amine)diphosphine PN(H)N(H)P ligand were synthesized. The structures of two complexes were characterized by X‐ray crystallography and high resolution mass spectrometry. The catalytic performances of cobalt complexes a and b for asymmetric transfer hydrogenation (ATH) of ketones under mild conditions were evaluated using 2‐propanolisopropanol as solvent and hydrogen source after being activated by 8 equivalents of base. Complex a showed a good reactivity for reduction of ketones, with a turnover number (TON) of up to 555, and a maximum enantiomeric excess (ee) value of up to 91 %. Complex b exhibited inertness for hydrogenation of ketones. Electronic structure studies on a and b were conducted to account for the function of ligands on the catalytic performances.

Recent Progress and Applications of Transition-Metal-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of Ketones and Imines through Dynamic Kinetic Resolution

AbstractBased on the ever-increasing demand for enantiomerically pure compounds, the development of efficient, atom-economical, and sustainable methods to produce chiral alcohols and amines is a major concern. Homogeneous asymmetric catalysis with transition-metal complexes including asymmetric hydrogenation (AH) and transfer hydrogenation (ATH) of ketones and imines through dynamic kinetic resolution (DKR) allowing the construction of up to three stereogenic centers is the main focus of the present short review, emphasizing the development of new catalytic systems combined to new classes of substrates and their applications as well.1 Introduction2 Asymmetric Hydrogenation via Dynamic Kinetic Resolution2.1 α-Substituted Ketones2.2 α-Substituted β-Keto Esters and Amides2.3 α-Substituted Esters2.4 Imine Derivatives3 Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution3.1 α-Substituted Ketones3.2 α-Substituted β-Keto Esters, Amides, and Sulfonamides3.3 α,β-Disubstituted Cyclic Ketones3.4 β-Substituted Ketones3.5 Imine Derivatives4. Conclusion

P,N,O type chiral imino- and aminophosphine ligands and their applications in Ru(II)-catalyzed asymmetric transfer hydrogen reactions

Chiral P,N,O type imino- (1a-d) and aminophosphine ligands (2a-d), substituted with methyl-, isopropyl-, phenyl- and benzyl groups, were synthesized and characterized by spectroscopic techniques such as NMR, FTIR and HRMS. The structure of the ligand 1c was also determined by single crystal X-ray diffraction analysis. The X-ray data revealed that compound 1c exhibited triclinic-P1 space group with C40H34NOP molecular formula. The catalytic performances of these imino- and aminophosphine ligands were tested in ruthenium catalyzed asymmetric transfer hydrogenation of aromatic ketones in 2-propanol. Ruthenium(II) complexes were generated in situ from Ru(cod)Cl2, Ru(dmso)4Cl2, Ru(PPh3)3Cl2 and [Ru(p-cymene)Cl2]2 precursors. According to the chromatographic analyses, isopropyl- substituted chiral aminophosphine ligand 2-((2-(diphenylphosphinyl)benzyl)amino)-3-methyl-1,1-diphenylbutan-1-ol (2b) and [Ru(cod)Cl2] combination were found to be the best catalyst system, affording (R)-enriched 1-(4-bromophenyl)ethanol in 85% ee and 98% conversion.

Cobalt-catalyzed asymmetric hydrogenation of ketones: A remarkable additive effect on enantioselectivity

A chiral cobalt pincer complex, when combined with an achiral electron-rich mono-phosphine ligand, catalyzes efficient asymmetric hydrogenation of a wide range of aryl ketones, affording chiral alcohols with high yields and moderate to excellent enantioselectivities (29 examples, up to 93% ee). Notably, the achiral mono-phosphine ligand shows a remarkable effect on the enantioselectivity of the reaction.

P-chirogenic Trost ligands mediated asymmetric hydrogenation of simple ketones

Herein, we report a highly active catalyst system consisting of (Rc,Rc,Rp,Rp)-P-chirogenic Trost ligand and [Ru(C6H6)Cl2]2 for asymmetric hydrogenation of simple ketones, affording the corresponding optically active alcohols in moderate enantioselectivity. A synergetic effect between P- and C-chirogenic centers of the P-chirogenic Trost ligands was observed in this asymmetric hydrogenation process.

Iridium-Catalyzed Asymmetric Hydrogenation of α-Fluoro Ketones via a Dynamic Kinetic Resolution Strategy.

The discrimination of a fluorine atom from a hydrogen atom has been challenging in asymmetric catalysis. We herein report iridium-catalyzed hydrogenation of α-fluoro ketones using a strategy of dynamic kinetic resolution. Both enantiomeric and diastereomeric selectivities were satisfactory in the preparation of β-fluoro alcohols. The DFT calculation revealed a C-F···Na charge-dipole interaction in the transition state of hydride transfer. This noncovalent interaction would be responsible for the diastereomeric control.

A simple and efficient asymmetric hydrogenation of heteroaromatic ketones with iridium catalyst composed of chiral diamines and achiral phosphines

An efficient iridium catalyst composed of a simple and commercially available o-methoxytriphenylphosphine and 9-Amino (9-deoxy) epi-cinchonine was applied to the asymmetric hydrogenation of heteroaromatic ketones. A range of simple heteroaromatic ketones could be hydrogenated with good to excellent enantioselectivities and high activities. In particular, thiophene ketones and furyl ketones furnished 98.6% ee with up to 2.18 × 104(1/h) TOF. This catalytic system can be of practical value.

Carboxyl Group-Directed Iridium-Catalyzed Enantioselective Hydrogenation of Aliphatic γ-Ketoacids

Although the transition metal-catalyzed asymmetric hydrogenation of aromatic ketones has been extensively explored, the enantioselective hydrogenation of aliphatic ketones remains a challenge becau...

The Stabilization Effect of π‐Backdonation Ligands on the Catalytic Reactivities of Amido‐Ene(amido) Iron Catalysts in the Asymmetric Transfer Hydrogenation of Ketones

A series of P–N–N–P iron complexes (1–3) were synthesized, characterized, and tested for their catalytic activities to explore the structure‐performance relationship of the catalyst precursors and intermediates. While the amino(imno) carbonyl complex (1) was highly active, the bis(amino) (2) and pyridyl‐amino (3) analogues were inactive. Stoichiometric reactions were studied to elucidate the mechanistic causes of the success and failure of these iron catalysts. Although 1a and 1b are active and stable at room temperature, 2a was found to be highly unstable under the catalytic conditions. Further electronic studies on 1a, 1b and 2a revealed that the π‐backdonation interactions in 1a and 1b can delocalize the electron density on the iron centers to the π‐bound ligand, explaining the elevated stability of the ene(amido)‐containing catalytic intermediates. Dearomatized pyridyl iron complexes (3b) were also inactive because they were too basic to be stable in the reaction solution.

Sulfone Group as a Versatile and Removable Directing Group for Asymmetric Transfer Hydrogenation of Ketones

AbstractThe sulfone functional group has a strong capacity to direct the asymmetric transfer hydrogenation (ATH) of ketones in the presence of [(arene)Ru(TsDPEN)H] complexes by adopting a position distal to the η6‐arene ring. This preference provides a means for the prediction of the sense of asymmetric reduction. The sulfone group also facilitates the formation of a range of reduction substrates, and its ready removal provides a route to enantiomerically enriched alcohols that would otherwise be extremely difficult to prepare by direct ATH of the corresponding ketones.

Sulfone Group as a Versatile and Removable Directing Group for Asymmetric Transfer Hydrogenation of Ketones.

The sulfone functional group has a strong capacity to direct the asymmetric transfer hydrogenation (ATH) of ketones in the presence of [(arene)Ru(TsDPEN)H] complexes by adopting a position distal to the η6‐arene ring. This preference provides a means for the prediction of the sense of asymmetric reduction. The sulfone group also facilitates the formation of a range of reduction substrates, and its ready removal provides a route to enantiomerically enriched alcohols that would otherwise be extremely difficult to prepare by direct ATH of the corresponding ketones.

Synthesis of cis‐1,2‐diol‐type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation

Two cis‐1,2‐diol‐type chiral ligands (T1 and T2) and their tri‐coordinated chiral dioxaborinane (T(1–2)B(1–2)) and four‐coordinated chiral dioxaborinane adducts with 4‐tert‐butyl pyridine sustained by N → B dative bonds (T(1–2)B(1–2)‐N) were synthesized and characterized by various spectroscopic techniques such as NMR (1H, 13C, and 11B), FT‐IR and UV–Vis spectroscopy, LC–MS/MS, and elemental analysis. It was suggested that both ferrocene and trifluoromethyl groups played key roles in the catalytic and biological studies because they could tune the solubility of the chiral dioxaborinane complexes and adjust the strength of intermolecular interactions. To assess the biological activities of newly synthesized chiral dioxaborinane compounds, DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical scavenging, reducing power, antibacterial, DNA binding, and DNA cleavage activities were tested. Then, all chiral dioxaborinane complexes were investigated as catalysts for the asymmetric transfer hydrogenation of various ketones under suitable conditions. The results indicated that the chiral dioxaborinane catalysts performed well with high yields.

Asymmetric transfer hydrogenation of ketones promoted by manganese(I) pre-catalysts supported by bidentate aminophosphines

A series of commercially available chiral amino-phosphines, in combination with Mn(CO)5Br, has been evaluated for the asymmetric reduction of ketones, using isopropanol as hydrogen source. With the most selective ligand, the corresponding manganese complex was synthesized and fully characterized. A series of ketones (20 examples) was hydrogenated in the presence of 0.5 mol% of the manganese pre-catalyst at 30 °C, affording the chiral alcohols in high yields with enantiomeric excesses up to 99%.

Design of Ru(II)-NHC-Diamine Precatalysts Directed by Ligand Cooperation: Applications and Mechanistic Investigations for Asymmetric Hydrogenation.

A modular synthesis of Ru(II)-NHC-diamine complexes from readily available chiral N-heterocyclic carbenes (NHCs) and chiral diamines is disclosed for the first time. The well-defined Ru(II)-NHC-diamine complexes show unique structure and coordination chemistry including an unusual tridentate coordination effect of 1,2-diphenylethylenediamine. The isolated air- and moisture-stable Ru(II)-NHC-diamine complexes act as versatile precatalysts for the asymmetric hydrogenation of isocoumarines, benzothiophene 1,1-dioxides, and ketones. Moreover, on the basis of the identification of reaction intermediates by stoichiometric reactions and NMR experiments, together with the DFT calculations, a possible catalytic cycle was proposed.