Asymmetric Transfer Hydrogenation Of Ketones Research Articles

Iron Catalysts Containing Amine(imine)diphosphine P-NH-N-P Ligands Catalyze both the Asymmetric Hydrogenation and Asymmetric Transfer Hydrogenation of Ketones

When activated with base, the iron(II) complexes with tetradentate amine(imine)diphosphine ligands, (S,S)-trans-[FeCl(CO)(PAr2-NH-N-PAr′2)]BF4 (1: Ar, Ar′ = Ph; 2: Ar = Ph, Ar′ = 4-MeC6H4; 3: Ar, Ar′ = 3,5-Me2C6H3), are very active for the asymmetric transfer hydrogenation (ATH) of ketones in KOtBu/2-propanol. For ATH, better enantioselectivity, but lower catalytic activity, was observed in general when using catalyst precursors with the bulkier dixylylphosphino groups compared to those with diphenylphosphino groups. The complexes were much less active for the pressure hydrogenation of ketones, where 1 and 2 produced racemic product alcohols, while 3 yielded chiral alcohols with an enantiomeric excess of up to 70% (R) at turnover frequencies up to 80 h–1 and turnover numbers of 100 for a range of ketones at 50 °C and 20 atm H2. This is a rare example of asymmetric pressure hydrogenation using an iron complex. Unlike the case of ATH, there is no effect on the rate upon the addition of KOtBu beyond the 2 eq...

Synthesis and characterization of novel chiral bidentate P,N-containing ligands and ruthenium(II) complex. The application in asymmetric transfer hydrogenation of ketones

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.

ChemInform Abstract: Second‐Generation Amino Acid Furanoside Based Ligands from D‐Glucose for the Asymmetric Transfer Hydrogenation of Ketones.

A novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium-catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ...

Amine(imine)diphosphine Iron Catalysts for Asymmetric Transfer Hydrogenation of Ketones and Imines

A rational approach is needed to design hydrogenation catalysts that make use of Earth-abundant elements to replace the rare elements such as ruthenium, rhodium, and palladium that are traditionally used. Here, we validate a prior mechanistic hypothesis that partially saturated amine(imine)diphosphine ligands (P-NH-N-P) activate iron to catalyze the asymmetric reduction of the polar bonds of ketones and imines to valuable enantiopure alcohols and amines, with isopropanol as the hydrogen donor, at turnover frequencies as high as 200 per second at 28°C. We present a direct synthetic approach to enantiopure ligands of this type that takes advantage of the iron(lI) ion as a template. The catalytic mechanism is elucidated by the spectroscopic detection of iron hydride and amide intermediates.

ChemInform Abstract: Synthesis of New Mono‐N‐tosylated Diamine Ligands Based on (R)‐(+)‐Limonene and Their Application in Asymmetric Transfer Hydrogenation of Ketones and Imines.

AbstractRuthenium catalysts (I) with chiral diamine ligands are successfully applied to the asymmetric transfer hydrogenation of ketones, imines, and iminium salts.

ChemInform Abstract: Use of Tridentate TsDPEN/Pyridine Ligands in Ruthenium‐Catalyzed Asymmetric Reduction of Ketones.

AbstractA series of enantiopure tridentate ligands based on 1,2‐diphenylethane‐1,2‐diamine, containing additional pyridine groups are prepared and applied in asymmetric transfer hydrogenation of ketones.

ChemInform Abstract: Imidazolium‐Based Organic—Inorganic Hybrid Silica as a Functional Platform Dramatically Boosts Chiral Organometallics Performance in Asymmetric Catalysis.

AbstractChiral rhodium and nickel catalysts immobilized on a phase‐transfer featured, imidazolium‐based, organic‐inorganic hybrid silica are applied to the asymmetric transfer hydrogenation of ketones and the asymmetric Michael addition of diethyl malonate.

Second‐Generation Amino Acid Furanoside Based Ligands from D‐Glucose for the Asymmetric Transfer Hydrogenation of Ketones

AbstractA novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium‐catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ketones, including the less‐studied heteroaromatic ketones. The ligands are based on amino acid hydroxyamides (pseudodipeptides), which are the most successful ligands previously used in asymmetric hydrogen transfer reactions. High enantioselectivities [up to 99 % enantiomeric excess (ee)] were achieved in the ATH of a wide range of aryl alkyl ketones by using catalysts generated in situ from [RhCl2Cp*]2 (Cp*=C5Me5) and thioamide ligands comprising a 3‐benzyl glucofuranoside backbone and a bulky isopropyl group in the α‐amino acid moiety. Interestingly, both enantiomers of the alcohol products can readily be obtained with high enantioselectivity by simply changing the absolute configuration of the α‐amino acid. The good performance can be extended to a very challenging class of industrially interesting heteroaromatic ketones (up to 99 % ee).

Tunable ferrocenyl-phosphinite ligands for the ruthenium(II)-catalyzed asymmetric transfer hydrogenation of ketones

We report here new examples of enantiomerically pure monodendate phosphinite ligands containing both a ferrocene moiety and NH bridging moiety adjacent to the stereocenter, as well as their ruthenium(II) dichloro complexes. The phosphinites based on ferrocenyl moiety possessing stereogenic center have been screened as ligands for ruthenium(II)-catalyzed transfer hydrogenation of aromatic ketones to give corresponding secondary alcohols using iso-PrOH as the hydrogen source in the presence of NaOH. Up to 99% conversion with 97% ee was obtained in the transfer hydrogenation of acetophenone derivatives. Furthermore, the catalytic properties of these catalysts based on ferrocenyl-phosphinite backbone are also discussed briefly. The structures of these ligand and their corresponding complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis.

Ru(II) pyridyl-based NNN complex catalysts for (asymmetric) transfer hydrogenation of ketones at room temperature

Ru(II) complexes bearing pyridyl-based benzimidazolyl-imidazolinyl tridentate NNN ligands were synthesized and structurally characterized. Their molecular structure was confirmed by X-ray crystallography. These complexes demonstrated good to excellent catalytic activity in the asymmetric transfer hydrogenation of ketones at room temperature, achieving up to 99% yields and 97% ee values.

Use of tridentate TsDPEN/pyridine ligands in ruthenium-catalysed asymmetric reduction of ketones

A series of enantiomerically pure tridentate ligands based on the 1,2-diphenylethane-1,2-diamine structure, containing additional pyridine groups, was prepared and tested in asymmetric transfer hydrogenation of ketones using Ru3(CO)12 as a metal source. Alcohols were formed in up to 93% ee in the best cases, and good results were obtained with ortho-haloarylketones.

Synthesis of new mono-N-tosylated diamine ligands based on (R)-(+)-limonene and their application in asymmetric transfer hydrogenation of ketones and imines

A synthetic procedure leading to the preparation of a new family of enantiopure mono-N-tosylated-1,2-diamines derived from (R)-(+)-limonene is described. (+)-Limonene was transformed into the appropriate N-tosyl derivative using N-tosylaziridination based on chloramine-T trihydrate. Subsequent ring opening by sodium azide afforded the corresponding isomeric azides. Finally, reduction of the azide function gave enantiomerically pure mono-N-tosylated-1,2-diamines. The ligands obtained proved to be effective in the asymmetric transfer hydrogenation protocol on aromatic ketones and imines.

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Enantiopure Osmium(II) Pybox Complexes

The complexes trans-[OsCl2(L){(S,S)-(i)Pr-pybox}] ((S,S)-(i)Pr-pybox = 2,6-bis[4'-(S)-isopropyloxazolin-2'-yl]pyridine, L = P(OMe)3 (1a), P(OEt)3 (2a), P(O(i)Pr)3 (3a), P(OPh)3 (4a), and cis-[OsCl2(L){(S,S)-(i)Pr-pybox}] (L = PPh3 (5a), P(i)Pr3 (6a), and PCy3 (7a)) have been synthesized from the complex trans-[OsCl2(η(2)-C2H4){(S,S)-(i)Pr-pybox}] via substitution of ethylene by phosphites and phosphines, respectively, under toluene reflux conditions. On the other hand, the synthesis of the complexes trans-[OsCl2(L){(R,R)-Ph-pybox}] (L = P(OMe)3 (1b) and cis-[OsCl2(L){(R,R)-Ph-pybox}] (L = PPh3 (5b), P(i)Pr3 (6b), and PCy3 (7b)) has been achieved from the complex trans-[OsCl2(η(2)-C2H4){(R,R)-Ph-pybox}] ((R,R)-Ph-pybox = 2,6-bis[4'-(R)-phenyloxazolin-2'-yl]pyridine under microwave irradiation. Complexes 1a-6a, 1b, 5b, and 6b have been assayed as catalysts for the asymmetric transfer hydrogenation (ATH) of ketones. Among the catalysts tested, the (i)Pr-pybox complexes trans-[OsCl2(L){(S,S)-(i)Pr-pybox}] (L = P(OMe)3 (1a), P(OEt)3 (2a), P(O(i)Pr)3 (3a), P(OPh)3 (4a)) have proven to be the most active catalysts for the reduction of a variety of aromatic ketones as nearly complete conversion and high enantioselectivity (up to 94%) are reached.

ChemInform Abstract: Ruthenium(II) Pyrazolyl—Pyridyl—Oxazolinyl Complex Catalysts for the Asymmetric Transfer Hydrogenation of Ketones.

Lowering the ketone: Ru(II) complexes containing a chiral pyridyl-based 1H-pyrazolyl-oxazolinyl NNN ligand were synthesized and structurally characterized by X-ray crystallographic studies. These complex catalysts efficiently catalyzed the asymmetric transfer hydrogenation of ketones, reaching up to 99 % ee for the desired products.

Quantum Chemical Calculations with the Inclusion of Nonspecific and Specific Solvation: Asymmetric Transfer Hydrogenation with Bifunctional Ruthenium Catalysts

Details of the mechanism of asymmetric transfer hydrogenation of ketones catalyzed by two chiral bifunctional ruthenium complexes, (S)-RuH[(R,R)-OCH(Ph)CH(Ph)NH(2)](η(6)-benzene) (Ru-1) or (S)-RuH[(R,R)-p-TsNCH(Ph)CH(Ph)NH(2)](η(6)-mesitylene) (Ru-2), were studied computationally by density functional theory, accounting for the solvation effects by using continuum, discrete, and mixed continuum/discrete solvation models via "solvated supermolecules" approach. In contrast to gas phase quantum chemical calculations, where the reactions were found to proceed via a concerted three-bond asynchronous process through a six-membered pericyclic transition state, incorporation of the implicit and/or explicit solvation into the calculations suggests that the same reactions proceed via two steps in solution: (i) enantio-determining hydride transfer and (ii) proton transfer through the contact ion-pair intermediate, stabilized primarily by ionic hydrogen bonding between the cation and the anion. The calculations suggest that the proton source for neutralizing the chiral RO(-) anion may be either the amine group of the cationic Ru complex or, more likely, a protic solvent molecule. In the latter case, the reaction may not necessarily proceed via the 16e amido complex Ru[(R,R)-XCH(Ph)CH(Ph)NH](η(6)-arene). The origin of enantioselectivity is discussed in terms of the newly formulated mechanism.

ChemInform Abstract: Homogeneous Asymmetric Transfer Hydrogenation of Ketones Using a Ruthenium Catalyst Anchored on Chitosan: Natural Chirality at Work.

AbstractThe asymmetric transfer hydrogenation of aromatic and aliphatic ketones is smoothly achieved using a RuCl2(p‐cymene) catalyst immobilized on pivaloyl‐functionalized chitosan as only source of chirality.

Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Ketones

Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Ketones

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Rhodium Block Copolymer Complexes in Aqueous Micelles

High activity and enantioselectivity were achieved in the rhodium-catalyzed asymmetric transfer-hydrogenation reactions of ketones in pure water using a novel amphiphilic block polypeptide ligand. The covalent linkage of the catalyst to the block copolymer plays a significant role and provides higher conversions and better recyclability than regular micellar or nonmicellar systems.

Application of Ruthenium Complexes of Triazole-Containing Tridentate Ligands to Asymmetric Transfer Hydrogenation of Ketones

The synthesis of a series of tridentate ligands based on a homochiral 1,2-diamine structure attached to a triazole group and their subsequent applications to the asymmetric transfer hydrogenation of ketones are described. In the best cases, alcohols of up to 93% ee were obtained. Although base is not required, the use of Ru(3)(CO)(12) as metal source is essential, indicating a unique mechanism for the formation of the active catalyst.

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Rhenium Complexes with Chiral Ferrocenylphosphane Ligands

AbstractWe have prepared a series of new rhenium complexes containing chiral ferrocenyldiphosphane ligands of the Josiphos family, starting from commercially available rhenium sources. These new ReV oxido and nitrido complexes, several of which have been characterized by X‐ray crystallography, are air‐ and moisture‐stable and are active catalysts in the asymmetric transfer hydrogenation of ketones using 2‐propanol as the hydrogen source in the presence of substoichiometric amounts of triethylamine (TEA). The reaction proceeds cleanly with good to excellent yields (50–99 %) but with moderate enantioselectivity (up to 58 % ee). A mechanism not involving hydridic species is proposed.