Bulky Achiral Triarylphosphines Mimic BINAP in Ru(II)‐ Catalyzed Asymmetric Hydrogenation of Ketones

In the present work, we report on catalysis of the enantioselective hydrogenation of ketones with Ru(II) complexes composed of cheap achiral monodentate phosphine ligands in combination with an enantiopure 1,2‐diamine, affording a variety of optically active secondary alcohols with high efficiency and enantioselectivity. The steric impact of achiral monophosphine ligands in Ru complexes was found to be a critical factor for the high enantioselectivity of the reaction. This finding throws some light on a long‐standing challenge, the high cost of chiral bisphosphine ligands, associated with an industrial application of the asymmetric hydrogenation of ketones.     

Modular Hydroxyamide and Thioamide Pyranoside‐Based Ligand Library from the Sugar Pool: New Class of Ligands for Asymmetric Transfer Hydrogenation of Ketones

A large library of pyranoside‐based hydroxyamide and thioamide ligands has been synthesized for asymmetric transfer hydrogenation in an attempt to expand the scope of the substrates to cover a broader range of challenging heteroaromatic and aryl/fluoroalkyl ketones. These ligands have the advantage that they are prepared from commercial D ‐glucose, D ‐glucosamine and α‐amino acids, inexpensive natural chiral feedstocks. By carefully selecting the ligand components (substituents/configurations at the amide/thioamide moiety, the position of amide/thioamide group and the configuration at C‐2), we found that pyranoside‐based thioamide ligands provided excellent enantioselectivities (in the best cases, ees of >99% were achieved) in a broad range of ketones, including the less studied heteroaromatics and challenging aryl/fluoroalkyls. Note that both enantiomers of the reduction products can be obtained with excellent enantioselectivities by simply changing the absolute configuration of the thioamide substituent.

     

Application of Tethered Ruthenium Catalysts to Asymmetric Hydrogenation of Ketones,and the Selective Hydrogenation of Aldehydes

An improved method for the synthesis of tethered ruthenium(II) complexes of monosulfonylated diamines is described, together with their application to the hydrogenation of ketones and aldehydes. The complexes were applied directly, in their chloride form, to asymmetric ketone hydrogenation, to give products in excess of 99% ee in the best cases, using 30 bar of hydrogen at 60 °C, and to the selective reduction of aldehydes over other functional groups.     

Asymmetric Transfer Hydrogenation of Ketones with Modified Grubbs Metathesis Catalysts: On the Way to a Tandem Process

Herein, we report the successful transformation of a 1^st generation Grubbs metathesis catalyst into an asymmetric transfer hydrogenation (ATH) catalyst. Upon addition of a chiral amine ligand, an alcohol and a base, the 1^st generation Hoveyda–Grubbs catalyst ( HG‐I ) was found to promote the enantioselective reduction of acetophenone to 1‐phenylethanol. After optimizing the order of addition and the reaction conditions, the substrate scope was assessed leading to enantiomeric excesses up to 97% ee. NMR experiments were run in order to get information about the in situ‐generated ATH catalyst. Furthermore, the possibility to perform olefin metathesis and ketone transfer hydrogenation sequentially in one pot was demonstrated, and the first tandem olefin metathesis–ketone asymmetric transfer hydrogenation was carried out.

     

Third‐Generation Amino Acid Furanoside‐Based Ligands from d‐Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope

A modular ligand library of α‐amino acid hydroxyamides and thioamides was prepared from 10 different N‐tert‐butyloxycarbonyl‐protected α‐amino acids and three different amino alcohols derived from 2,3‐O‐isopropylidene‐α‐d ‐mannofuranoside. The ligand library was evaluated in the half‐sandwich ruthenium‐ and rhodium‐catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium‐hydroxyamide and the rhodium‐thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α‐alkylation/asymmetric transfer hydrogenation of acetophenones and 3‐acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.

     

Asymmetric Hydrogenation of Ketones with Polymer‐Bound BINAP/Diamine Ruthenium Catalysts

The BINAP/1,2‐diphenylethylenediamine RuCl₂ complexes bound to a polystyrene resin act as precatalysts for asymmetric hydrogenation of various simple ketones. The enantioselectivity, turnover number, and turnover frequency are comparable to those attained under homogeneous conditions.     

Polystyrene‐Supported Enantiopure 1,2‐Diamines: Development of a Most Practical Catalyst for the Asymmetric Transfer Hydrogenation of Ketones

Chlorosulfonylated polystyrene, a commodity resin, reacts with enantiopure 1,2‐diamines to afford, in a single step, high loading catalytic resins involving monosulfonylated 1,2‐diamino moieties. These functional polymers form stable (p‐cymene)ruthenium chloride [RuCl(p‐cymene)] complexes that efficiently catalyze (down to S/C=150) the asymmetric transfer hydrogenation (ATH) of alkyl aryl ketones with formic acid‐triethylamine under essentially solvent‐free (down to 0.25 mL mmol⁻¹) reaction conditions. Among these resins, the immobilized version of TsDPEN stands out as a most practical catalyst for ATH: Uniformly high enantioselectivities are achieved with its use at low catalyst loading, and the resin can be recycled with virtually no limits.     

Synthesis of Planar Chiral Shvo Catalysts for Asymmetric Transfer Hydrogenation

A new type of planar chiral Shvo catalysts, where the chirality is based solely on different substitution flanking the C O function, was prepared and used for transfer hydrogenation of imines and ketones. The reduction of ketimines represented by N‐(1‐phenylethylidene)aniline and prochiral ketones such as phenyl trifluoromethyl ketone with 2‐propanol was efficiently catalyzed by 0.5 mol% of the chiral Shvo catalyst to give high yields of the corresponding reduction products with the enantioselectivities in the range 45% to 64% ee.

     

钌-手性膦配体催化剂在不对称催化氢化反应中的应用

较详细的综述了钌-手性膦配体催化剂在不对称催化氢化反应中的最新应用进展，主要从钌-手性膦配体催化剂在芳基丙烯酸(萘普生、布洛芬等)、酰胺类化合物、酮酯等方面的不对称催化反应中的应用进行综述，文章从催化剂活性、立体选择性、转化率和对映选择性等角度讨论了各种合成方法的优点及不足。     

Magnetically Recoverable Nanoparticles: Highly Efficient Catalysts for Asymmetric Transfer Hydrogenation of Aromatic Ketones in Aqueous Medium

Two magnetic chiral iridium and rhodium catalysts were prepared via directly postgrafting 1,2‐diphenylethylenediamine‐derived organic silica or 1,2‐cyclohexanediamine‐derived organic silica onto the silica‐coated iron oxide nanoparticles followed by complexation with iridium(III) or rhodium(III) complexes. During the asymmetric transfer hydrogenation of aromatic ketones in aqueous medium, the magnetic chiral catalysts exhibited high catalytic activities (up to 99% conversion) and enantioselectivities (up to 92% ee). Both catalysts could be recovered easily by magnetic separation and be reused ten times without significantly affecting their catalytic activities and enantioselectivities.     

Highly Efficient Asymmetric Hydrogenation of Alkyl Aryl Ketones Catalyzed by Iridium Complexes with Chiral Planar Ferrocenyl Phosphino-Thioether Ligands

Iridium complexes of planar-chiral ferrocenyl phosphine-thioether ligands were tested in the hydrogenation of simple ketones. Optimization of the conditions led to a highly active catalytic system with turnover numbers up to 915 and turnover frequencies up to ca. 250 h⁻¹. Furthermore, very high enantioselectivities (up to >99 %) together with complete conversions were obtained for the asymmetric hydrogenation of various acetophenones at 10 °C.     

Direct and Transfer Hydrogenation of Ketones and Imines with a Ruthenium N‐Heterocyclic Carbene Complex

The dihydride ruthenium N‐heterocyclic carbene complex Ru(IMes)(PPh₃)₂CO(H)₂ ( 1 ) (IMes=1,3‐dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene) is an efficient catalyst for both direct hydrogenation and transfer hydrogenation of ketones and imines, in the absence of base.     

Ruthenium Phenylindenyl Complex as an Efficient Transfer Hydrogenation Catalyst

An efficient and green protocol for the transfer hydrogenation of carbonyl and imine compounds is presented. The transformations are catalysed by the inexpensive and easily synthesised complex [RuCl(PPh₃)(3‐phenylindenyl)]. Its catalytic activity was compared to that of the most commonly encountered ruthenium complexes in transfer hydrogenation reactions involving several protypical substrates.     

过渡金属络合物对酮类化合物不对称催化氢化反应研究进展

对近年来过渡金属络合物对酮类化合物不对称催化氢化反应研究进展进行了综述。     

Synthesis of Ruthenium Hydride Complexes Containing beta‐Aminophosphine Ligands Derived from Amino Acids and their use in the H2‐Hydrogenation of Ketones and Imines

The new complexes RuHCl(PPh₂CH₂CHRNH₂)₂ and RuHCl(PPh₂CH₂CHRNH₂)(R‐ binap), R=H (Pgly), R=Me [(R)‐Pala] were prepared by the substitution of the PPh₃ ligands in RuHCl(PPh₃)₃ or RuHCl(PPh₃)[(R)‐binap] with beta‐aminophosphines derived from amino acids. The complex trans‐RuHCl(Pgly)[(R)‐binap] has been characterized by X‐ray crystallography. The complex trans‐RuHCl[(S)‐Ppro]₂ where (S)‐Ppro is derived from proline was also prepared and characterized by X‐ray crystallography. These were used as catalyst precursors in the presence of a base (KOPr‐i or KOBu‐t) for the hydrogenation of various ketones and imines to the respective alcohols and amines with H₂ gas (1–11 atm) at room temperature. Acetophenone was hydrogenated to (S)‐1‐phenylethanol in low ee (up to 40%) when catalyzed by the enantiomerically pure complexes. These complexes are especially active in the hydrogenation of sterically congested and electronically deactivated ketones and imines and are selective for the hydrogenation of CO bonds over CC bonds.     

ansa‐Ruthenium(II) Complexes of R2NSO2DPEN‐(CH2)n(η6‐Aryl) Conjugate Ligands for Asymmetric Transfer Hydrogenation of Aryl Ketones

New 3^rd generation designer ansa‐ruthenium(II) complexes featuring N,C‐alkylene‐tethered N,N‐dialkylsulfamoyl‐DPEN/η⁶‐arene ligands, exhibited good catalytic performance in the asymmetric transfer hydrogenation (ATH) of various classes of (het)aryl ketones in formic acid/triethylamine mixture. In particular, benzo‐fused cyclic ketones furnished 98 to >99.9% ee using a low catalyst loading.

     

An Ion‐Pair Immobilization Strategy in Rhodium‐Catalyzed Asymmetric Transfer Hydrogenation of Aromatic Ketones

A chiral diamine‐based homogeneous cationic rhodium catalyst was developed and two heterogeneous cationic rhodium catalysts were obtained via the encapsulation of the homogeneous cationic rhodium catalyst within Me‐SBA‐15 and Me‐SBA‐16. All these catalysts presented excellent catalytic activities and high enantioselectivities in ultrasound‐promoted asymmetric transfer hydrogenation of aromatic ketones and represent a successful use of the ion‐pair immobilization strategy. More importantly, the encapsulation of the cationic rhodium functionality within Me‐SBA‐16 had an obvious high recyclability, in which the recycled catalyst could be reused nine times without significantly affecting its enantioselectivity, showing good potential in industrial application.     

β‐Hydroxycarboxylic Acids from Simple Ketones by Carboxylation and Asymmetric Hydrogenation

We present a new asymmetric synthesis of β‐hydroxycarboxylic acids from ketones, performed by carboxylation using CO₂ followed by asymmetric hydrogenation. First, the carboxylation of ketones gives β‐ketocarboxylic acids. The effects of temperature, reaction time, and amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) promoter on the carboxylation were investigated. The DBU can be recycled. For the second step, the asymmetric hydrogenation of these β‐ketocarboxylic acids, we determined the effect of solvent choice, H₂ pressure, and substrate substitution. Hydrogenation yield and enantioselectivity are solvent‐dependent, and the mechanism could proceed through hydrogenation of either the enol or the keto forms of the bound substrate. This synthesis is industrially advantageous due to the limited number of reactants required, their low‐cost, and the potential for recycling unused materials.     

Iron Complexes with Chiral N/P Macrocycles as Catalysts for Asymmetric Transfer Hydrogenation

The present account describes the development of chiral, C₂-symmetric N/P macrocyclic ligands that attune to the size and electronic properties of the iron(II) ion to give robust complexes under catalysis conditions. This is not trivial, as the complexes of base metals are substantially less stable than those of precious metals. Also, as these N₂P₂ macrocycles feature stereogenic P atoms, the control of the stereochemistry at phosphorus is a key synthetic issue. Still, as the macrocyclic effect was insufficient to give robust catalysts under hydrogen transfer conditions, we had to dig deeper into the toolbox of coordination chemistry and use strong-field ancillary ligands other than CO, specifically isonitriles, which additionally offer a further handle to tune the catalyst. The reward was the discovery of the first iron(II) catalyst for the asymmetric transfer hydrogenation of polar double bonds that is highly enantioselective for a broad scope of substrates.