Novel Chiral PNNP-Ru Complexes:Synthesis and Application in Asymmetric Transfer Hydrogenation of Ketones

The efficient catalytic systems generated in situ from RuCl2（PPh3）3 and chiral ligands N,N-bis[2-（di-o-tolylphosphino）-benzyl]cyclohexane-1,2-diamine（2） were employed for asymmetric transfer hydrogenation of aromatic ketones, giving the corresponding optically active alcohols with high activities（up to 99% conversion） and excellent enantioselectivities（up to 96% e.e.） under mild conditions. The chiral ruthenium（Ⅱ） complex （R,R）-3 has been prepared and characterized by NMR and X-ray crystallography.

Development of efficient solid chiral catalysts with designable linkage for asymmetric transfer hydrogenation of quinoline derivatives

Developing chiral solid catalysts for asymmetric catalysis is desirable for the elimination of homogeneous catalysis flaws but remains an immense challenge.Herein,we report the immobilization of TsDPEN on SBA‐15 with an ionic liquid(IL)linkage via the one‐pot reaction of imidazole‐TsDPEN‐N‐Boc with 3‐(trimethoxysilyl)propyl bromide in the SBA‐15 mesopores.After coordination to Rh,the chiral solid catalysts could efficiently catalyze quinoline transfer hydrogenation,achieving 97%conversion with 93%ee,which was comparable to their homogeneous counterparts.The chiral solid catalyst with the IL linkage afforded much higher turnover frequency than that without the IL linkage(93 h^(–1)vs.33 h^(–1)),attributed to the phase transfer and formate‐enriching ability of the IL linkage.Furthermore,the effect of the pH on the reaction rate of the solid catalyst was investigated,preventing reaction rate retardation during the catalytic process.The tuning of the linkage group is an efficient approach for catalytic activity improvement of immobilized chiral catalysts.

Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

Antidepressant duloxetine （1） was prepared via asymmetric transfer hydrogenation of 3-（dimethylamino）-1-（thiophen-2- yl）propan-1-one （3）. The Ru（Ⅱ）, Rh（Ⅲ） and Ir（Ⅲ） complexes of several chiral ligands were examined as the catalyst and （S,S）-N-tosyl-1,2-diphenyl ethylenediamine （TsDPEN）-Ru（Ⅱ） complex was found to provide good yield and excellent enantioselectivity. 2007 Ming Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Heterocyclic Diaryl Ketones:Facile Access to Key Intermediate of Baloxavir

Transition metal-catalyzed asymmetric transfer hydrogenation has been proven to be a powerful approach for the synthesis of chiral alcohols.Herein,a highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene-tethered TsDPEN-based Rh(ll)catalyst has been successfully developed,and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU(1,8-diazabicyclo[5.4.0]undec-7-ene)with high yields and enantioselectivities.With this method,the asymmetric reduction of 7,8-difluorodibenzo[b,e]thiepin-11(6H)-one has been realized,providing the key intermediate of baloxavir marboxil with>99% yield and>99% ee at a substrate/catalyst molar ratio of 1000.

Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α-Chiral Primary Amines

Although it offers a direct route to access synthetically valuableα-chiral primary amines,asymmetric transfer hydrogenation of NH imines has been rarely studied,due in large part to the inaccessibility and instability of NH imines.Herein,we report a Rh-catalyzed asymmetric transfer hydrogenation of a kind of novel and stable NH imines which are prepared via condensation of easily available sulfonylated 2'-aminoacetophenones with NH3 in methanol.With this method,enantioenriched chiral 2-(1-aminoalkyl)anilines,which are privileged pharmacore groups,have been synthesized with good functional group compatibility,and with up to 99%ee.A gram-scale reaction using 0.2 mol%of catalyst has been successfully performed to highlight the practicality.Furthermore,the products can be derivatized into enantiopure bioactive molecules as well as chiral tridentate ligands for metal catalysis.

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

The asymmetric reduction of carbonyl compounds by means of the Ru-chiral diphosphine-chiral diamine catalysts is widely useful in organic synthesis where high levels of enantioselectivities have been attributed to multiple ligand chiral elements as well as essential stereochemical matching synergies within them.Described here is the design and discovery of new pincer-type Ru-catalysts that feature only single stereogenic element within ligands,yet the such significantly simplified structure is demonstrated to be well competent for effecting asymmetric reductions as well as kinetic resolutions over a broad range of highly functionalized ketones/alcohols,including heteroaryl substituted substrates that were challenging by known catalyst systems.Alcohols were furnished not only in excellent enantioselectivities,but with turnover numbers(up to 100,000 TONs)that reach the highest levels known to date in asymmetric transfer hydrogenation of ketones.This work should help shed light on the intricate origin of enantioselection in these important processes,and further stimulate rational understanding as well as optimization of chiral catalysts towards efficiency and simplicity.

Synthesis of novel chiral N,P-containing multidentate ligands and their applications in asymmetric transfer hydrogenation

Novel chiral PN_4-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.

Asymmetric transfer hydrogenation of ketones catalyzed by nickel complex with new PNO-type ligands

The new polydentate mixed-N,P,O chiral ligands have been synthesized by the condensation of bis（o-formylphenyl）- phenylphosphane and R-phenylglycinol in CHCl_3,and fully characterized by IR,NMR and EIMS spectra.These ligands were employed with a simple Ni complex Ni（PPh_s）_2Cl_2 in 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.

Asymmetric Transfer Hydrogenation of Diaryl Ketones with Ethanol Catalyzed by Chiral NCP Pincer Iridium Complexes

The use of a chiral(NCP)Ir complex as the precatalyst allowed for the discovery of asymmetric transfer hydrogenation of diaryl ketones with ethanol as the hydrogen source and solvent.This reaction was applicable to various ortho-substituted diaryl keontes,affording benzhydrols in good yields and enantioselectivities.This protocol could be carried out in a gram scale under mild reaction conditions.The utility of the catalytic system was highlighted by the synthesis of the key precursor of(S)-neobenodine.

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 P_(x)N_(y)-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')-CyP_(2)N_(4)(L_(5))with 2 mol%of catalyst loading,affording highly valuable chiral alcohols with up to 95%ee.

Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones

Novel chiral multidentate P3N4-type ligand has been synthesized and characterized by NMR and HRMS.Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand（R,R,R,R）-3 and IrCl（CO）（PPh3）2exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee.

New Chiral Ligand N-Toluenesulfonyl-2,2′-dimethoxy-6,6′-diaminobiphenyl for Catalytic Asymmetric Transfer Hydrogenation of Ketones

A new chiral ligand N p toluenesulfonyl 2,2′ dimethoxy 6,6′ diaminobiphenyl (Ts DMBDPPA) was prepared from 2,2′ dimethoxy 6,6′ diaminobiphenyl via N tosylation. Its Ru(II) complex was effective catalysts for catalytic asymmetric transfer hydrogenation of aromatic ketones (with ee 's up to 69.3%).

Immobilization of chiral Rh catalyst on glass and application to asymmetric transfer hydrogenation of aryl ketones in aqueous media

A chiral catalyst, Cp＊RhTsDPEN （Cp＊ = pentamethyl cyclopentadiene, TsDPEN = substitutive phenylsulfonyl-l,2-diphenylethylenediamine）, was synthesized and immobilized at the surface of glass. The immobilized catalyst exhibited good catalytic efficiency for asymmetric transfer hydrogenation of aromatic ketones in water with HCOONa as hydrogen source.

Highly efficient catalysts derived from planar chiral ferrocenes for asymmetric transfer hydrogenation of ketones

Planar chiral ferrocenes 1 and its diastereoisomer 2 were found to be good lig-ands for. the ruthenium catalyzed asymmetric transfer hydrogenation of ketones with i-PrOH as hydrogen source under refluxing in the presence of sodium hydroxide. The results showed that the absolute configuration of alcohol seemed to be governed by the central chirality in the oxazoline ring instead of the planar chirality. At a ratio of 1:2 for Ru:ligand, 3000:1 S/C and >100,000/h?1 TOF were observed for acetophenone. For propiophenone 99% yield and 85% e.e. were obtained.

Enantioselective Transfer Hydrogenation of Aromatic Ketones Catalyzed by New Diaminodiphosphine Ru(Ⅱ) Complexes

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New Chiral Metal Cluster Systems for Catalytic AsymmetricSyntheses of Chiral Alcohols

The efficient chiral Ru 3(CO) 12 systems were prepared in situ from Ru 3(CO) 12 and various chiral diimino-or diamino-diphosphine tetradentate ligands. The systems have been used for the asymmetric transfer hydrogenation of propiophenone in 2-propanol, leading to 1-phenyl-1-propanol in a 98% yield and 96% e.e. The IR study suggests that the carbonyl hydride anion [HRu 3(CO) 11]- most probably exists as a principal species under the reaction conditions. The high chiral efficiency may be due to the synergetic effect produced by the neighboring ruthenium atoms and a special chiral micro-environment involving the polydentate ligand and the Ru 3 framework.

Synthesis of novel chiral tetraaza ligands and their application in enantioselective transfer hydrogenation of ketones

Novel chiral tetraaza ligands（R）-N,N′-bis[2-（piperidin-1-yl）benzylidene]propane-l,2-diamine 6 and（S）-N-[2-（piperidin-l- 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.

Synthesis of Chiral 2-Aroyl-l-tetralols： Asymmetric Transfer Hydrgenation of 2-Aroyl-l-tetralones via Dynamic Kinetic Resolution

The dynamic kinetic resolution of 2-aroyl-l-tetralones was achieved via asymmetric transfer hydrogenation using （S,S）-RuCl（p-cymene）TsDPEN （TsDPEN=N-（tosyl）-1,2-diphenylethylenediamine） in formic acid/triethylamine （5 ： 2, molar ratio）, afforded the desired products in good yields （up to 85%） with diastereomeric ratio up to 〉99 ： 1 and high enantiomeric excesses （up to 〉99%）. The absolute configuration of major the product was con- firmed by X-ray crystal structure analysis.

Novel chiral C_2-symmetric multidentate aminophosphine ligands for use in catalytic asymmetric reduction of ketones

A series of novel chiral C_2-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.