Direct Amide Synthesis from Alcohols and Amines by Phosphine‐Free Ruthenium Catalyst Systems

Amides are synthesized directly from alcohols and amines in high yields using an in situ generated catalyst from easily available ruthenium complexes such as the (p‐cymene)ruthenium dichloride dimer, [Ru(p‐cymeme)Cl₂]₂, or the (benzene)ruthenium dichloride dimer, [Ru(benzene)Cl₂]₂, an N‐heterocyclic carbene (NHC) ligand, and a nitrogen containing L‐type ligand such as acetonitrile. The phosphine‐free catalyst systems showed improved or comparable activity compared to previous phosphine‐based catalytic systems. The in situ generated catalyst from [Ru(benzene)Cl₂]₂, an NHC ligand, and acetonitrile showed excellent activity toward reactions with cyclic secondary amines such as piperidine and morpholine.     

Iron‐Catalyzed Highly Enantioselective Reduction of Aromatic Ketones with Chiral P2N4‐Type Macrocycles

Novel P₂N₄‐donors containing chiral 22‐membered macrocyclic ligands have been synthesized and the structures have been determined by an X‐ray diffraction study. The catalytic systems in situ generated from triiron dodecarbonyl, Fe₃(CO)₁₂, and the chiral macrocyclic ligand exhibited high activity (TOF up to 1940 h⁻¹) and excellent enantioselectivity with up to 99% ee in the asymmetric transfer hydrogenation of various aromatic ketones.     

Rhodium complexes containing chiral P-donor ligands as catalysts for asymmetric hydrogenation in non conventional media

Abstract  

Rhodium-catalysed asymmetric hydrogenation using P-donor ligands, such as new fluorinated (R)-BINOL and azadioxaphosphabicyclo[3.3.0]octane derivatives was carried out in different reaction media such as organic solvent (CH₂Cl₂), ionic liquid ([BMI][PF₆]), supercritical carbon dioxide (scCO₂) and [BMI][PF₆]/scCO₂ mixture. The best enantioselectivities were obtained in neat [BMI][PF₆], allowing a recycling up to ten times without activity loss. However, the enantioselectivity was lost due to ligand leaching. The ionic liquid phase containing rhodium molecular species was supported on functionalized multi-walled carbon nanotubes in order to improve the recycling, but unfortunately the asymmetric induction was lost upon catalyst immobilization.     

Ru/ZIF-8 with a chiral modifier for asymmetric hydrogenation of acetophenone

A series of Ru/ZIF-8 (Zeolitic imidazolate framework) catalysts was prepared in the different impregnation solvents and characterized by ICP, XRD, TEM, and N₂ adsorption. The obtained catalysts exhibited different catalytic performances in the presence of achiral modifier triphenylphosphine (TPP) and chiral modifier (1S,2S)-1,2-diphenylethylenediamine [(1S,2S)-DPEN] for asymmetric hydrogenation of acetophenone. Ethanol was found to be the most effective impregnation solvent, while low activity and enantioselectivity were observed for water. The prepared Ru/ZIF-8 catalyst was stable and could be reused at least five times without significant loss in activity and entantioselectivity.     

Reduced graphene oxide supported chiral Ni particles as magnetically reusable and enantioselective catalyst for asymmetric hydrogenation

A reduced graphene oxide (rGO) supported chiral-modified Ni catalyst was synthesized, characterized and employed for asymmetric hydrogenation. The prepared hybrid catalyst could produce each enantiomer with d- or l-tartaric acid as chiral modifier and exhibited a high TOF (20160 h⁻¹) and enantioselectivity (enantiomeric excess, 98.5%) for asymmetric hydrogenation of methyl acetoacetate. The high catalytic activity and enantioselectivity were mainly attributed to the unique properties of the support rGO, as it had a large specific surface area to sustain and stabilize Ni particles and its high charge carrier mobility could enable the readily transfer of electrons in the reaction process. Besides, the catalyst could also gain an enhanced reactant sorption with the support of rGO, thus achieved a greatly catalysis enhancement. The ferromagnetism of Ni made the catalyst easier for separation and reuse. The catalytic and recycling performance of the prepared chiral Ni catalyst demonstrated that rGO was indeed a promising support to improve activity, enantioselectivity and durability of catalysts, and the prepared catalysts were promising reusable heterogeneous catalysts for asymmetric hydrogenation.     

Chiral N,N'-dioxides: new ligands and organocatalysts for catalytic asymmetric reactions

Homochiral catalysts that can effect asymmetric transformations are invaluable in the production of optically active molecules. Researchers are actively pursuing the design of new ligands and organocatalysts by exploiting concepts derived from the application of bifunctional and C(2)-symmetric catalysts. Many homochiral catalysts containing amines, ethers, alcohols, and phosphines as electron-pair donors have been successfully developed. Amine N-oxides are highly polar substances. Despite their pronounced capacity as electron-pair donors, N-oxides have been underutilized in asymmetric reactions; they have only made a visible impact on the field in the preceding decade. Systematic studies have instead largely focused on pyridine- or quinoline-based scaffolds in organosilicon and coordination chemistry. The application of chiral tertiary amine N-oxides has not been widely pursued because of the difficulty of controlling the chirality at the tetrahedral nitrogen of the N-oxide moiety. In this Account, we outline the design of a new family of C(2)-symmetric N,N'-dioxides from readily available chiral amino acids. We then discuss the application of these chiral amine N-oxides as useful metal ligands and organocatalysts for asymmetric reactions. The high nucleophilicity of the oxygen in N-oxides is ideal for organocatalytic reactions that rely on nucleophilic activation of organosilicon reagents. These catalysts have been successfully applied in the asymmetric addition of trimethylsilylcyanide to aldehydes, ketones, aldimines, and ketimines, with good yields and excellent enantioselectivities. Asymmetric organocatalytic chlorination of β-ketoesters with N-chlorosuccinimide has also been achieved through hydrogen bond activation. The molecular framework of these N,N'-dioxides, with their multiple O-donors, also serves as a new tetradentate ligand that can coordinate a range of metal ions, including Cu(I), Cu(II), Ni(II), Mg(II), Fe(II), Co(II), In(III), Sc(III), La(III), Y(III), Nd(III), and others. These versatile metal complexes are efficient catalysts for a variety of asymmetric reactions. Asymmetric cycloadditions have been achieved with these chiral Lewis acid catalysts. We have also found success with asymmetric nucleophilic additions to C═O or C═N bonds; substrates include 3-substituted 2-oxindoles, alkenes, enamides, enecarbamates, diazoacetate esters, nitroalkanes, glycine Schiff bases, and phosphate. Notably, the first catalytic asymmetric Roskamp reaction was realized, which was successful because of the high efficiency of the catalyst. Asymmetric conjugate additions between α,β-unsaturated compounds and nucleophiles such as nitroalkane, malonate, thioglycolate, and indoles have been accomplished. The first asymmetric haloamination of chalcones was discovered, and the reaction proceeded with high regio- and enantioselectivity. In some cases, we were able to reduce the catalyst loading to just 0.01-0.05 mol % while maintaining excellent outcomes. Some particularly interesting phenomena were observed over the course of the research. These include a remarkable amplification of the asymmetry in a sulfa-Michael reaction, as well as the reversal of enantioselectivity after alteration of the central metal or the subunits of the ligand in two other reactions. These unusual results have facilitated a deeper understanding of the catalytic mechanism.     

Controlled Reversible Anchoring of η6‐Arene/TsDPEN‐ Ruthenium(II) Complex onto Magnetic Nanoparticles: A New Strategy for Catalyst Separation and Recycling

A new catalyst separation and recycling protocol combining magnetic nanoparticles and host‐guest assembly was developed. The catalyst, (η⁶‐arene)[N‐(para‐toluenesulfonyl)‐1,2‐diphenylethylenediamine]ruthenium trifluoromethanesulfonate [Ru(OTf)(TsDPEN)(η⁶‐arene)] bearing a dialkylammonium salt tag, was easily separated from the reaction mixtures by magnet‐assisted decantation, on basis of the formation of a pseudorotaxane complex by using dibenzo[24]crown‐8‐modified Fe₃O₄ nanoparticles. The ruthenium catalyst has been successfully reused at least 5 times with the retention of enantioselectivity but at the expense of relatively low catalytic activities in the asymmetric hydrogenation of 2‐methylquinoline.     

Enantioselective Hydrogenation of the Tetrasubstituted C=C Bond of Enamides Catalyzed by a Ruthenium Catalyst Generated in situ

The enantioselective hydrogenation of enamides bearing an endocyclic tetrasubstituted carbon‐carbon double bond has been performed in the presence of ruthenium catalyst precursors prepared from Ru(cod)(methallyl)₂, Duphos, or BPE as optically active ligand and HBF₄. This promising catalytic system makes possible the selective cis‐hydrogenation with satisfactory enantioselectivities (up to 72% ee) for this type of tetrasubstituted double bonds.     

Novel N,N‐Bidentate Ligands for Enantioselective Copper(I)‐ Catalyzed Allylic Oxidation of Cyclic Olefins

New N,N‐bidentate Schiff base ligands containing the 2‐quinolyl moiety proved to be effective in conferring high reactivity and moderate to high enantioselectivity (up to 84% ee) to the copper(I)‐catalyzed asymmetric allylic oxidation of various cylic olefins with tert‐butyl perbenzoate. As copper(I) sources, we employed copper(II) triflate/phenylhydrazine [Cu(OTf)₂/PhNHNH₂] and tetra(acetonitrile)copper hexafluorophosphate [Cu(CH₃CN)₄PF₆]. Using the same N,N‐bidentate Schiff base ligand, the former showed high reactivity and the latter showed high enantioselectivity.     

Asymmetric transfer hydrogenation of ketones by N,N-containing quinazoline-based ruthenium(II) complexes

The novel set of quinazoline-based chiral ligands was synthesized starting from optically pure amino acids. Coordination with RuCl₂(PPh₃)dppb gave ruthenium(II) N-heterocyclic complexes 4b–d. The structure of complex 4b was fully illuminated by X-ray crystallography. The steric environment of these chiral ruthenium complexes 4b–d was evaluated in asymmetric transfer hydrogenation (ATH) of prochiral ketones in the presence of NaOⁱPr by using 2-propanol as the hydrogen source and solvent. The resultant catalytic system can achieve very good enantioselectivities (up to 91%) and high yields (up to 99%).     

Highly Enantioselective Hydrogenation of Quinoline and Pyridine Derivatives with Iridium‐(P‐Phos) Catalyst

The use of a chiral iridium catalyst generated in situ from the (cyclooctadiene)iridium chloride dimer, [Ir(COD)Cl]₂, the P‐Phos ligand [4,4′‐bis(diphenylphosphino)‐2,2′,6,6′‐tetramethoxy‐3,3′‐bipyridine] and iodine (I₂) for the asymmetric hydrogenation of 2,6‐substituted quinolines and trisubstituted pyridines [2‐substituted 7,8‐dihydroquinolin‐5(6H)‐one derivatives] is reported. The catalyst worked efficiently to hydrogenate a series of quinoline derivatives to provide chiral 1,2,3,4‐tetrahydroquinolines in high yields and up to 96% ee. The hydrogenation was carried out at high S/C (substrate to catalyst) ratios of 2000–50000, reaching up to 4000 h⁻¹ TOF (turnover frequency) and up to 43000 TON (turnover number). The catalytic activity is found to be additive‐controlled. At low catalyst loadings, decreasing the amount of additive I₂ was necessary to maintain the good conversion. The same catalyst system could also enantioselectively hydrogenate trisubstituted pyridines, affording the chiral hexahydroquinolinone derivatives in nearly quantitative yields and up to 99% ee. Interestingly, increasing the amount of I₂ favored high reactivity and enantioselectivity in this case. The high efficacy and enantioselectivity enable the present catalyst system of high practical potential.     

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.     

Monomeric complexes of Re(CO)3+ ion with tridentate N∩N∩O−ligands — Schiff base derivatives of salicylic aldehyde

Simple synthetic procedures, reactions of Re(CO)₅Cl with potentially tridentate N∩N∩OH ligands (Schiff bases prepared from aliphatic or aromatic amines and salicylic aldehyde) lead to formation of monomeric complexes of fac-Re(CO)₃⁺ ion. Three obtained complexes have been characterized by means of elemental analyses and IR, UV–vis, and EI-MS techniques. Molecular structures of the synthesized species were investigated using X-ray diffraction measurements. Depending on the nature of N∩N∩OH ligand the investigated Schiff bases form with fac-Re(CO)₃⁺ ion bidentate or tridentate chelates with N∩N, N∩O⁻ or N∩N∩O⁻ coordination types.     

Ferrocene‐Based Chiral Phosphine‐Triazines: A New Family of Highly Efficient P,N Ligands for Asymmetric Catalysis

The presence of the additional heterocyclic nitrogen atoms in chiral P,N ligands has an important influence on the asymmetric catalysis, and a clear trend was observed in the present research that the enantioselectivity and reactivity were significantly increased by raising the number of heterocyclic nitrogen atoms in these P,N ligands. Through finely tuning the number of heterocyclic nitrogen atoms, a new family of ferrocene‐based chiral phosphine‐triazine ligands with three heterocyclic nitrogen atoms has been developed and successfully applied in Pd‐catalyzed asymmetric allylic substitution. Up to 99% ee with 99% yield of allylic alkylation products and 94% ee of allylic amination products have been obtained by the use of ligand (R_c,S_p)‐ 1f with a 4,6‐diphenoxy‐1,3,5‐triazine moiety.     

A Novel Ruthenium‐Phosphorus Amorphous Alloy Catalyst for Maltose Hydrogenation to Maltitol

A ruthenium‐phosphorus (Ru‐P) amorphous alloy catalyst was prepared by chemical reduction of ruthenium(III) ions [Ru³⁺] with hypophosphite [H₂PO₂⁻] in aqueous solution and was applied to the liquid‐phase hydrogenation of maltose. In comparison with other reference catalysts, Ru‐P showed significant activity as evident in the order: Ru‐P> Ru‐B≫ Ni‐P> Co‐P≫ Raney Ni. Furthermore, this catalyst was also found to be more durable during this hydrogenation process. Special emphasis was laid on a comparative study of Ru‐P and Ru‐B catalysts to get an insight into the excellent catalytic performances of Ru‐P.     

Highly Enantioselective Synthesis of Chiral Tetrahydroquinolines and Tetrahydroisoquinolines by Ruthenium‐Catalyzed Asymmetric Hydrogenation in Ionic Liquid

Asymmetric hydrogenation reactions of quinolines and 3,4‐dihydroisoquinolines using the chiral cationic ruthenium complex Ru(TsDPEN) [TsDPEN=N‐(p‐toluenesulfonyl)‐1,2‐diphenylethylenediamine] as catalyst in neat imidazolium ionic liquids have been investigated. The catalytic performance was influenced by the anion of the ionic liquids for both substrate classes. A range of 2‐alkyl‐substituted 1,2,3,4‐tetrahydroquinolines and 1‐alkyl‐substituted 1,2,3,4‐tetrahydroisoquinolines was obtained in high yields with up to >99% ee. Interestingly, the hydrogenation of quinoline derivatives bearing a carbonyl group was selective for the CN (quinoline) over the CO (ketone) bonds, while such a unique chemoselectivity was not observed in methanol. Furthermore, the ruthenium catalysts could be easily recycled at least 5 times in the asymmetric hydrogenation of 3,4‐dihydroisoquinoline by solvent extraction. To further facilitate the recovery of catalyst and reduce the use of organic solvent, a thin film of ionic liquid containing Ru(TsDPEN) was supported on silica gels. This supported ionic liquid‐phase catalyst was effective in the asymmetric hydrogenation of quinoline, and could be recycled at least 6 times by simple filtration.

     

Ruthenium(III) Complexes of Heterocyclic Tridentate (ONN) Schiff Base: Synthesis,Characterization and its Biological Properties as an Antiradical and Antiproliferative Agent

The current work reports the synthesis, spectroscopic studies, antiradical and antiproliferative properties of four ruthenium(III) complexes of heterocyclic tridentate Schiff base bearing a simple 2′,4′-dihydroxyacetophenone functionality and ethylenediamine as the bridging ligand with RCHO moiety. The reaction of the tridentate ligands with RuCl₃·3H₂O lead to the formation of neutral complexes of the type [Ru(L)Cl₂(H₂O)] (where L = tridentate NNO ligands). The compounds were characterized by elemental analysis, UV-vis, conductivity measurements, FTIR spectroscopy and confirmed the proposed octahedral geometry around the Ru ion. The Ru(III) compounds showed antiradical potentials against 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, with DPPH scavenging capability in the order: [(PAEBOD)RuCl₂] > [(BZEBOD)RuCl₂] > [(MOABOD)RuCl₂] > [Vit. C] > [rutin] > [(METBOD)RuCl₂], and ABTS radical in the order: [(PAEBOD)RuCl₂] < [(MOABOD)RuCl₂] < [(BZEBOD)RuCl₂] < [(METBOD)RuCl₂]. Furthermore, in vitro anti-proliferative activity was investigated against three human cancer cell lines: renal cancer cell (TK-10), melanoma cancer cell (UACC-62) and breast cancer cell (MCF-7) by SRB assay.     

In situ synthesis and dielectric properties of copper(II) and nickel(II) chiral Schiff base complexes

Two chiral Schiff base-containing complexes, [Cu(L¹)](ClO₄)₂·H₂O (1, L¹ = (S,S)-N1,N2-bis((1H-imidazol-4-yl)methylene)cyclohexane-1,2-diamine) and [Ni(L²)₂](ClO₄)₂ (2, L² = (S,S)-N1-((1H-imidazol-4-yl)methylene)cyclohexane-1,2-diamine) were synthesized from the reaction mixture of 1H-imidazole-4-carbaldehyde, (S,S)-1,2-diaminocyclohexane and Cu(ClO₄)₂·6H₂O or Ni(ClO₄)₂·6H₂O in methanol. Single-crystal X-ray diffraction analyses reveal that the in situ generated chiral Schiff base ligands L¹ and L² are bisubstituted and monosubstituted, respectively, corresponding to the different metal ions Cu^II and Ni^II. Variable-frequency and -temperature dielectric properties of 1 and 2 have been studied.     

Integration of Homogeneous and Heterogeneous Catalytic Processes for a Multi-step Conversion of Biomass: From Sucrose to Levulinic Acid, γ-Valerolactone, 1,4-Pentanediol, 2-Methyl-tetrahydrofuran, and Alkanes

The multi-step conversion of sucrose to various C₅-oxygenates and alkanes was achieved by integrating various homogeneous and heterogeneous catalytic systems. We have confirmed that the dehydration of sucrose to levulinic and formic acids is currently limited to about 30–40% in the presence of H₂SO₄, HCl, or Nafion NR50 in water. Performing the dehydration in the presence of a P(m-C₆H₄SO₃Na)₃ modified ruthenium catalyst under hydrogen resulted in the in situ conversion of levulinic acid to γ-valerolactone (GVL). Levulinic acid can be hydrogenated to GVL quantitatively by using P(m-C₆H₄SO₃Na)₃ modified ruthenium catalyst in water or Ru(acac)₃/PBu₃/NH₄PF₆ catalyst in neat levulinic acid. Formic acid can be used for the transfer hydrogenation of levulinic acid in water in the presence of [(η⁶-C₆Me₆)Ru(bpy)(H₂O)][SO₄] resulting in GVL and 1,4-pentanediol. The hydrogenation of levulinic acid or GVL can be performed to yield 1,4-pentanediol and/or 2-methyl-tetrahydrofuran (2-Me-THF). The hydrogenolysis of 2-Me-THF in the presence of Pt(acac)₂ in CF₃SO₃H resulted in a mixture of alkanes. We have thus demonstrated that the conversion of carbohydrates to various C₅-oxygenates and even to alkanes can be achieved by selecting the proper catalysts and conditions, which could provide a renewable platform for the chemical industry.     

A Simple Approach to Unsymmetric Atropoisomeric Bipyridine N,N′‐Dioxides and Their Application in Enantioselective Allylation of Aldehydes

The [2+2+2] cyclotrimerization of 1‐isoquinolinyl‐1,7‐octadiyne with benzonitrile catalyzed by CpCo(CO)₂ opened a new pathway for a synthesis of unsymmetrical axially chiral bipyridine N,N′‐dioxides. The N,N′‐dioxide 3a was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyltrichlorosilane. The allylation took place with even 1 % of the catalyst with an enantioselectivity up to 87 % ee.