Asymmetric Transfer Hydrogenation Of Ketones Research Articles

Asymmetric Transfer Hydrogenation of Ketones Improved by PNN-Manganese Complexes.

Chiral manganese(I) complexes that contain carbocyclic-fused 8-amino-5,6,7,8-tetrahydroquinolinyl groups that are appended with distinct para-R substituents have proven to be effective catalysts in the asymmetric transfer hydrogenation (ATH) of a wide range of ketones (48 examples). Notably, Mn2 proved to be the most productive catalyst, allowing an outstanding turnover number of 8300 with catalyst loadings as low as 0.01 mol %. Furthermore, this catalytic protocol shows considerable promise for applications in the synthesis of chiral drugs such as Lusutrombopag.

Enhancing enantioselectivity of manganese catalyst for asymmetric transfer hydrogenation of ketones through P,N,N-chelation of a cyclooctyl pyridine

A new ferrocene-based chiral PNN pincer ligand (L1) was successfully applied in Mn-catalyzed asymmetric transfer hydrogenation (ATH) of ketones (37 examples), leading to high activities (up to 4000 TON with 48 h) and excellent enantioselectivities (up to >99 % ee) for their product alcohols. The combined coordination and catalytic studies led to the conclusion that PNN pincer ligand L1 proved higher enantioselectivity in ATH than that observed by PN bidentate analogue L0. Furthermore, DFT calculations and control experiments highlighted the significance of the cyclooctyl group among these cycloalkyl motifs in the Mn-catalysts, resulting in enhanced enantioselectivity (up to 99 % ee), and disclosed the stereocontrol with the assistance of an attractive aromatic π-π stacking interaction between substrate and catalyst in the catalytic process.

Synthesis, characterization and theoretical studies of tris-cyclometalated rhodium(III) complexes: applications to asymmetric transfer hydrogenation of ketones

This paper presents the synthesis of {Rh[PyCH=C(O)Rn]3} complexes, where R1 = 4-cyanophenyl (L1), R2 = 3-nitrophenyl (L2), and R3 = 4-fluorophenyl (L3). These complexes were derived from the reactions of potassium hexachlororhodate(III) with related pyridinium ylides: PyCH=C(O)C6H4-p-CN (Y1), PyCH=C(O)C6H4-m-NO2 (Y2), and PyCH=C(O)C6H4-p-F (Y3). The reactions were carried out in methanol-water mixtures under mild conditions. The synthesized complexes were characterized using FT-IR, ESI-MS, multinuclear NMR (1H and 13C), and elemental analysis techniques (CHN). Furthermore, these Rh(III) compounds demonstrated excellent catalytic activity, high turnover number (TON), and turnover frequency (TOF) in the hydrogenation of various ketones, resulting in a series of alcohol products with outstanding yields and efficiencies. To investigate the structures of L1, L2, and L3, density function theory (DFT) calculations were performed at the BP86/def2-SVP level of theory. The study employed natural bond orbital analysis (NBO) and energy-decomposition analysis (EDA) to examine the strength and nature of the donor-acceptor bonds between the pyridinium ylide (Y) and Rh fragments in the complexes. Additionally, variations in natural orbitals for chemical valence (NOCV) were investigated.

Catalytic performance of Noyori–Ikariya-type ruthenium complex with tethered syn-ULTAM ligand for the asymmetric transfer hydrogenation of ketones

The ruthenium complex of the tethered syn-ULTAM ligand, i.e. syn-3-(α-aminobenzyl)-benzo-γ-sultam, has been evaluated for the asymmetric transfer hydrogenation (ATH) of a variety of ketones in formic acid/triethylamine mixture. Its performance was similar to the established Noyori–Ikariya-type catalysts for the reduction of benzo-fused cyclic ketones, but the enantioselectivity for the reduction of acetophenone was only moderate. The syn-ULTAM-based catalyst was particularly efficient and enantioselective for ATH of the sterically demanding α,α-disubstituted ketones. Moreover, we report a divergent ATH of 2-phenyl-1,3-indandione to either cis-2-phenyl-1-indanol, or cis,trans-2-phenyl-1,3-indandiol.

Polymeric Micelles with Chiral Diamine-Ru(II) Catalysts for Asymmetric Transfer Hydrogenation of Ketones in Water

Polymeric Micelles with Chiral Diamine-Ru(II) Catalysts for Asymmetric Transfer Hydrogenation of Ketones in Water

Pincer Ru with a single stereogenic identity for highly efficient asymmetric transfer hydrogenation of ketones

Pincer Ru with a single stereogenic identity for highly efficient asymmetric transfer hydrogenation of ketones

Asymmetric transfer hydrogenation of ketones catalyzed by chiral macrocyclic cobalt(II) complexes

Using easily available CoBr2 and chiral cyclic PxNy-type ligands as starting materials, novel chiral cyclic cobalt(II) complexes could be conveniently prepared. Furthermore, we obtained the single crystals suitable for X-ray diffraction to confirm the structures of these cobalt(II) complexes. The asymmetric transfer hydrogenation (ATH) of ketones catalyzed by these well-designed cobalt(II) complexes was investigated. Among them, cobalt(II) complex containing chiral macrocyclic iminophosphine ligand CyP2N4 exhibited high catalytic activity and enantioselectivity (up to 99% ee). Density functional theory (DFT) calculations suggested that cobalt(II) complex (R,R,R',R')-CyP2N4-Co(II) (C1) is easier to form metal hydride, which is the key intermediate during the enantioselective transfer hydrogenation reaction. Study results also revealed that the unique macrocyclic structure of complex C1 could form a special microenvironment around cobalt ion. Therefrom the substrate coordinated with the central metal along this specific reaction channel during the asymmetric catalytic reaction, resulting high enantioselectivity.

Mechanochemical, Water‐Assisted Asymmetric Transfer Hydrogenation of Ketones Using Ruthenium Catalyst

AbstractAsymmetric catalytic reactions are among the most convenient and environmentally benign methods to obtain optically pure compounds. The aim of this study was to develop a green system for the asymmetric transfer hydrogenation of ketones, applying chiral Ru catalyst in aqueous media and mechanochemical energy transmission. Using a ball mill we have optimized the milling parameters in the transfer hydrogenation of acetophenone followed by reduction of various substituted derivatives. The scope of the method was extended to carbo‐ and heterocyclic ketones. The scale‐up of the developed system was successful, the optically enriched alcohols could be obtained in high yields. The developed mechanochemical system provides TOFs up to 168 h−1. Our present study is the first in which mechanochemically activated enantioselective transfer hydrogenations were carried out, thus, may be a useful guide for the practical synthesis of optically pure chiral secondary alcohols.

Tethered ruthenium(II) η6-arene complexes: assessing the potential of benzylic substituents to control metal-centred chirality, and applications in asymmetric transfer hydrogenations of ketones

The synthesis and characterisation of a small series of tethered ruthenium(II) η6-arene complexes is described, where a single benzylic substituent is examined as a route to enforcing chirality at the metal centre upon ligation of a tethered bidentate ligand. The application of these complexes as catalysts in the asymmetric transfer hydrogenation of ketones is described, with moderate enantioselectivities confirming the validity of the approach.

Amino Acid Derived Chiral Aminobenzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of Ketones

Amino Acid Derived Chiral Aminobenzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of Ketones

Design of Iridium N-Heterocyclic Carbene Amino Acid Catalysts for Asymmetric Transfer Hydrogenation of Aryl Ketones

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of α-amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

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.

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.

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.

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%.

Stepwise Construction of Ru(II)Center Containing Chiral Thiourea Ligand on Graphene Oxide: First Efficient, Reusable, and Stable Catalyst for Asymmetric Transfer Hydrogenation of Ketones

Heterogenization of homogenous catalysts on solid support has attracted tremendous attention in organic synthesis due to the key benefits of heterogenized catalysts such as easy recovery and reusability. Although a considerable number of heterogenized catalysts are available, to the best of our knowledge, there is no efficient and reusable heterogenized catalyst reported for asymmetric reactions to date. Herein, we prepared a [RuCl2(η6-p-cymene)]/chiralthiourea ligand covalently bonded to graphene nanosheets (G-CLRu(II), where G represents graphene oxide (GO), CL denotes chiral N-((1-phenylethyl)carbamothioyl)acetamide and Ru(II) symbolizes [RuCl2(η6-p-cymene)]), for the asymmetric transfer hydrogenation of ketones. Five simple steps were involved in the preparation of the G-CLRu(II) catalyst. The structure of G-CLRu(II) was investigated by means of various spectroscopic and microscopic techniques. Coordination mode and covalent bonding involved in the G-CLRu(II) structure we reconfirmed. G-CLRu(II) demonstrated good catalytic performance towards the asymmetric transfer hydrogenation of ketones (conversion of up to 95%, enantiomeric excesses (ee) of up to 99%, and turnover number (TON) and turnover frequency (TOF) values of 535.9 and 22.3 h−1, respectively). A possible mechanism is proposed for the G-CLRu(II)-catalyzed asymmetric transfer hydrogenation of ketones. Recovery (~95%), reusability (fifth cycle, yield of 89% and ee of 81%), and stability of G-CLRu(II) were found to be good. We believe that the present stepwise preparation of G-CLRu(II) opens a new door for designing various metal-centered heterogenized chiral catalysts for asymmetric synthesis.

An iron variant of the Noyori hydrogenation catalyst for the asymmetric transfer hydrogenation of ketones.

We report the design of a new iron catalyst for the asymmetric transfer hydrogenation of ketones. This type of iron catalyst combines the structural characteristics of the Noyori hydrogenation catalyst (an axially chiral 2,2'-bis(phosphino)-1,1'-binaphthyl fragment and the metal-ligand bifunctional motif) and an ene(amido) group that can activate the iron center. After activation by 8 equivalents of potassium tert-butoxide, (SA,RP,SS)-7a and (SA,RP,SS)-7b are active but nonenantioselective catalysts for the transfer hydrogenation of acetophenone and α,β-unsaturated aldehydes at room temperature in isopropanol. A maximum turnover number of 14480 was observed for (SA,RP,SS)-7a in the reduction of acetophenone. The right combination of the stereochemistry of the axially chiral 2,2'-bis(phosphino)-1,1'-binaphthyl group and the carbon-centered chiral amine-imine moiety in (SA,RP,RR)-7b' afforded an enantioselective catalyst for the preparation of chiral alcohols with moderate to good yields and a broad functional group tolerance.