Ruthenium Carbene Research Articles

Hydrogenative Cyclopropanation and Hydrogenative Metathesis

AbstractThe unusual geminal hydrogenation of a propargyl alcohol derivative with [CpXRuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap.

Synthesis and Evaluation of Ruthenium 2‐Alkyl‐6‐mercaptophenolate Catalysts for Olefin Metathesis

A series of ruthenium carbene catalysts containing 2‐sulfidophenolate bidentate ligand with an ortho‐substituent next to the oxygen atom were synthesized. The molecular structure of ruthenium carbene complex containing 2‐isopropyl‐6‐sulfidophenolate ligand was confirmed through single crystal X‐ray diffraction. An oxygen atom can be found in the opposite position of the N‐heterocyclic carbene (NHC) based on the steric hindrance and strong trans‐effects of the NHC ligand. The ruthenium carbene catalyst can catalyze ring‐opening metathesis polymerization (ROMP) reaction of norbornene with high activity and Z‐selectivity and cross metathesis (CM) reactions of terminal alkenes with (Z)‐but‐2‐ene‐1,4‐diol to give Z‐olefin products (Z/E ratios, 70:30–89:11) in low yields (13%–38%). When AlCl3 was added into the CM reactions, yields (51%–88%) were considerably improved and process becomes highly selective for E‐olefin products (E/Z ratios, 79:21–96:4). Similar to other ruthenium carbene catalysts, these new complexes can tolerate different functional groups.

Selectivity in Ring‐Closing Metathesis: Synthesis of Propellanes and Angular Aza‐tricycles

AbstractSeveral naturally occurring alkaloids contain quaternary carbon centers attached to a nitrogen atom. An efficient synthetic protocol has been developed to assemble indoline‐fused propellanes over aza‐tricyclic carbazole derivatives via a selective ring‐closing metathesis employing Grubbs’ first‐generation catalyst. Electronic factors seem to play a critical role in the outcomes. The structure of propellanes and angular aza‐tricyclic compounds are confirmed by catalytic hydrogenation sequence. To expand the synthetic utility of these propellanes and aza‐tricycles, Suzuki‐Miyaura cross‐coupling reaction has been employed to generate functionalized polycycles. Fourteen ruthenium carbene catalysts are examined to synthesize propellanes and aza‐tricycles.magnified image

Bimolecular Cross-Metathesis of a Tetrasubstituted Alkene with Allylic Sulfones.

Exquisite control of catalytic metathesis reactivity is possible through ligand‐based variation of ruthenium carbene complexes. Sterically hindered alkenes, however, remain a generally recalcitrant class of substrates for intermolecular cross‐metathesis. Allylic chalcogenides (sulfides and selenides) have emerged as “privileged” substrates that exhibit enhanced turnover rates with the commercially available second‐generation ruthenium catalyst. Increased turnover rates are advantageous when competing catalyst degradation is limiting, although specific mechanisms have not been defined. Herein, we describe facile cross‐metathesis of allylic sulfone reagents with sterically hindered isoprenoid alkene substrates. Furthermore, we demonstrate the first example of intermolecular cross‐metathesis of ruthenium carbenes with a tetrasubstituted alkene. Computational analysis by combined coupled cluster/DFT calculations exposes a favorable energetic profile for metallacyclobutane formation from chelating ruthenium β‐chalcogenide carbene intermediates. These results establish allylic sulfones as privileged reagents for a substrate‐based strategy of cross‐metathesis derivatization.

Transformations of biomass-based levulinate ester into γ-valerolactone and pyrrolidones using carbon nanotubes-grafted N-heterocyclic carbene ruthenium complexes

Abstract As a renewable biomass-based compound with wide applications in food additives, fine chemical synthesis and fuels, γ-valerolactone (GVL) has attached much attention. While, pyrrolidones are widely used in pharmaceutical, agrochemical, material industrial and other chemical production. In this research, we demonstrated transformations of biomass-based ethyl levulinate (EL) into GVL and pyrrolidones by using heterogeneous catalysts (CNT-Ru-1) with N-heterocyclic carbene ruthenium (NHC-Ru) complex grafted on multi-walled carbon nanotube (CNT). The Ru catalyst showed high efficiency on EL hydrogenation to GVL with both EL conversion and GVL yield exceeding 99%. Moreover, the Ru catalyst readily promoted reductive amination of EL in the presence of various amines for pyrrolidone synthesis. Finally, the Ru catalyst was also applicable to hydrogenation of various carbonyl compounds for the synthesis of the corresponding alcohols with excellent catalytic performance. The research provides insight for heterogenizing the homogeneous noble metal-based catalysts with high catalytic active for biomass-based transformations.

Synthesis, catalysis, and DFT study of a ruthenium carbene complex bearing a 1,2-dicarbadodecaborane (12)-1,2-dithiolate ligand.

A ruthenium carbene catalyst containing a 1,2-dicarbadodecaborane(12)-1,2-dithiolate ligand was synthesized, and the structure was determined by single crystal X-ray diffraction. This new ruthenium carbene catalyst can catalyze the ring opening metathesis polymerization (ROMP) reaction of norbornene to give the corresponding Z-polymer (Z/E ratio, 98 : 2) in high yield (93%); ring opening cross metathesis (ROCM) reactions of norbornene/5-norbornene-2-exo, 3-exo-dimethanol with styrene or 4-fluorostyrene to give the corresponding Z-olefin products (Z/E ratios, 97 : 3-98 : 2), respectively, in high yields (73%-88%); cross metathesis (CM) reactions of terminal alkenes with (Z)-but-2-ene-1,4-diol to give high Z-olefin products in low yields; homometathesis reactions of terminal alkenes to give olefin products in low yields. Like other ruthenium carbene catalysts, the new complex tolerates many different functional groups. DFT calculations were also performed in order to understand the process of forming Z-olefin products and the decomposition process of catalysts.

A 3,4-dimercapto-3-cyclobutene-1,2-dione-chelated ruthenium carbene catalyst for Z-stereoretentive/stereoselective olefin metathesis

A ruthenium carbene catalyst chelated with a 3,4-dioxocyclobut-1-ene-1,2-dithiolate ligand was synthesized and its molecular structure was determined by single-crystal X-ray diffraction. The Ru catalyst had excellent catalytic activity with high yields and good Z/E ratios for the ring opening metathesis polymerization (ROMP) of norbornene (yield: 96%/Z/E: 86 : 14) and 1,5-cyclooctadiene (yield: 86%/Z/E: 91 : 9) and for ring opening cross metathesis (ROCM) reactions of norbornene/5-norbornene-2-exo, 3-exo-dimethanol with styrene (yields: 64%-92%/Z/E: 97 : 3-98 : 2) or 4-fluorostyrene (yield: 46%-94%/Z/E: 98 : 2). The catalyst also had high Z-stereoretentivity (91 : 9-98 : 2) for cross-metathesis (CM) reactions of terminal olefins with (Z)-2-butene-1,4-diol. More importantly, the catalyst had moderate Z-stereoselectivity for homometathesis reactions of terminal olefins giving cis-olefins as the major products (Z/E ratios of 70 : 30-77 : 23). Like other Ru carbene complexes, the catalyst tolerates many different functional groups. The presented data, supported by DFT calculations, show that our catalyst, bearing a chelating 3,4-dioxocyclobut-1-ene-1,2-dithiolate ligand, exhibits higher stability towards air than Hoveyda's stereoretentive complex systems.

Cationic abnormal N-heterocyclic carbene ruthenium complexes as suitable precursors for the synthesis of heterobimetallic compounds.

The cationic abnormal N-heterocyclic carbene complex [Ru(OAc)(dppe)(PC)]Br (2b) (PC = bidentate phosphine-carbene ligand) has been obtained by treatment of the neutral derivative RuBr(OAc)(PPh3)(PC) (2a) with dppe in THF. Reaction of 2b with Ag2O afforded the heterobimetallic complex Ru(OAc)(dppe)(PC)AgBr (2c) which can be easily transmetallated with [Ir(cod)Cl]2 giving Ru(OAc)(dppe)(PC)IrCl(cod) (2d). Similarly, [{Ru(OAc)(PC)(PC')}2Ag][AgBr2] (1b) reacts with [Ir(cod)Cl]2 with formation of Ru(OAc)(PC)(PC')IrCl(cod) (1e). All complexes were characterized by NMR in solution and by single crystal X-ray diffraction studies in solid state. For the cationic complexes the 1H NMR resonance of the carbene-proton is considerably down-field shifted (δ > 9 ppm) with respect to that of the neutral derivatives. Cyclic voltammetry and differential pulse voltammetry studies show that the Ru-centered redox process occurs at lower potential (ΔE > 100 mV) after transmetallation with iridium, suggesting an interaction of the two metals along the π-system of the heterocycle ligand. These complexes display catalytic activity in transfer hydrogenation of acetophenone in 2-propanol with a significant influence of Ir and Ag centers on the Ru moiety. The synthesis of the imidazolyl-based N-heterocyclic dicarbene Ru-Ir complexes, which entails the easy metallation of the reactive cationic abnormal N-heterocyclic carbene Ru complexes with Ag2O, represents a suitable pathway for the preparation of heterometallic ruthenium complexes.

Looking for the Noncyclic(amino)(alkyl)carbene Ruthenium Catalyst for Ethenolysis of Ethyl Oleate: Selectivity Is on Target.

A wide set of 65 diverse Ru metathesis catalysts was investigated in the ethenolysis reaction of biosourced ethyl oleate to allow the comparison between the catalyst structure and its activity and selectivity. Handling of the oleic substrate, weighing of the catalysts, and charging the reactor were done in air, with exclusion of a glovebox or Schlenk techniques. A catalyst bearing the unsymmetrical N-heterocyclic ligand featuring a thiophene fragment (Ru-63) was selected to offer the best combination between high selectivity and sufficient activity under conditions mimicking oil industry practice. A proof-of-concept large-scale ethenolysis experiment was also done with the selected catalyst to prove its high selectivity at the 1 L scale reaction with a 90% pure non-distilled substrate.

Ruthenium-Catalyzed Intramolecular Double Hydroalkoxylation of Internal Alkynes.

Intramolecular double hydroalkoxylation of internal alkynes could be achieved using a Grubbs-type ruthenium carbene complex or its modified species to deliver a series of bridged- and spiroacetal derivatives in moderate to good yields. This study represents a new example of nonmetathetic reactions catalyzed by Grubbs-type ruthenium carbene complexes.

Synthesis and evaluation of Naphthalene-1, 8-dithiolate chelating ruthenium carbene catalyst for Z-Stereoretentive olefin metathesis

A highly Z-stereoretentive olefin metathesis ruthenium carbene catalyst containing a naphthalene-1,8-dithiol ligand was synthesized, and the structure was determined by single-crystal X-ray diffraction. The new ruthenium carbene catalyst could catalyze cross-metathesis reactions of terminal alkenes with (Z)-but-2-ene-1,4-diol to give highly Z-stereoretentive products. Like to other ruthenium carbene catalysts, the new complex tolerates many different functional groups.

CO2 Hydrogenation to Formate with Immobilized Ru‐Catalysts Based on Hybrid Organo‐Silica Mesostructured Materials

AbstractThe hydrogenation of CO2 to formic acid can be carried out by numerous homogenous catalysts, while efficient heterogeneous catalysts are rare. In this work, we successfully synthesize an immobilized lutidine‐derived pincer‐type N‐heterocyclic carbene ruthenium complex based on a mesoporous organo‐silica hybrid material using sol‐gel direct synthesis in the presence of structure directing agents and click chemistry as the two key pillars of this strategy. This material efficiently catalyzes the hydrogenation of CO2 into formate with turnover numbers reaching 18′000 within 24 hours, surpassing the performance of the corresponding homogeneous complexes.

Ruthenium Complexes Bearing Thiophene-Based Unsymmetrical N-Heterocyclic Carbene Ligands as Selective Catalysts for Olefin Metathesis in Toluene and Environmentally Friendly 2-Methyltetrahydrofuran.

Three mono-N-heterocyclic carbene (NHC) ruthenium 2-isopropoxybenzylidene (10 a-c) and one bis(NHC) indenylidene complex (8) bearing an unsymmetrical N-heterocyclic carbene ligand were synthesized and structurally characterized by single-crystal X-ray diffraction. The catalytic activity of the newly obtained complexes were evaluated in ring-closing metathesis (RCM) and ene-yne (RCEYM) reactions in toluene and environmentally friendly 2-MeTHF under air. The results confirmed that although all tested reactions can be successfully mediated by catalysts 10 a-c, their general reactivity is lower than the benchmark all-purpose Ru catalysts with symmetrical NHC ligands. However, the latter cannot compete with specialized ruthenium complex 10 a in industrially relevant self-CM of terminal olefins in neat conditions.

Imine-N-Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p-Cymene Anticancer Complexes: A Structure-Activity Relationship Study.

A family of novel imine-N-heterocyclic carbene ruthenium(II) complexes of the general formula [(η6 -p-cymene)Ru(C^N)Cl]PF6 - (where C^N is an imine-N-heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine-N-heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD+ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC50 =14.36 μm), with an approximately 1.5-fold better activity than the clinical platinum drug cisplatin (IC50 =21.30 μm) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.

Understanding the Microstructure of Poly(p-phenylenevinylene)s Prepared by Ring-Opening Metathesis Polymerization Using 13C-Labeled Paracyclophanediene Monomers

Selectively main chain 13C-labeled poly(p-phenylenevinylene)s (PPVs) were synthesized by ring-opening metathesis polymerization (ROMP) of 13C-labeled dialkoxy-substituted [2,2] paracyclophane-1,9-dienes (M) using the Grubbs second generation ruthenium carbene complex (G2). Analysis of the natural abundance and 13C-labeled PPVs by NMR spectroscopy showed no main chain structural defects for these polymers. Comparison of the in situ 1H and 13C NMR spectroscopy during the ROMP of labeled and unlabeled monomer enabled the active ruthenium carbene chain ends present during the initiation and propagation reaction to be definitively characterized. Using 13C NMR spectroscopy, the regiochemistry of the propagation of the asymmetric monomer M with G2 was found to be essentially regiorandom.

Protonated water-soluble N-heterocyclic carbene ruthenium(II) complexes: Synthesis, cytotoxic and DNA binding properties and molecular docking study

New benzimidazolium salts 1a-d having methylpyridine group on the side chain, have been synthesized and reacted with Ag2O to produce Ag(I)-N-heterocyclic carbene (NHC) complexes 2a-d. Ag(I)-N-heterocyclic carbene (NHC) complexes were used as a carben transfer agents to synthesize water-soluble ruthenium(II)-NHC complexes 4a-d. All synthesized compounds were fully characterized by 1H and 13C NMR and HRMS spectroscopic techniques. Anticancer potential and IC50 values of ruthenium(II)-NHC complexes were evaluated by MTT assay against human colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines. The IC50 value of water-soluble ruthenium(II)-NHC complex 4d demonstrated remarkable cytotoxic activity against Caco-2 (18.0 ± 1) and MCF-7 (23.8 ± 0.5) cell lines. Also, 4d has better DNA binding capacity than 4a-c. DS 2017 R2 was used to exert molecular docking for understanding interactions between the water-soluble ruthenium(II)-NHC complexes and DNA. These complexes have been highlighted as a new type of drug.

Investigation of potential hybrid capacitor property of chelated N-Heterocyclic carbene Ruthenium(II) complex

The synthesis of chelated ruthenium(II) complex type Ru(η6-HMB) (NHC)Cl (NHC=N-heterocyclic carbene, HMB = hexamethylbenzene) is presented. The ruthenium(II)-NHC complex 6 was obtained in good yield and was fully characterised by NMR spectroscopy, X-ray diffraction and HRMS analysis. Electrochemical analysis by cyclic voltammetry (CV) revealed reversible redox behaviour at the ruthenium centre in 6. DFT studies and the catalytic activity of complex 6 on transfer hydrogenation reaction of aryl ketones are also presented. The potential hybrid capacitor applications of Ru-NHC complex is discussed and reported firstly in the literature. It was found that the highest performance was found at 20.1 F/g, which is a promising result for energy storage applications.

Ruthenium Carbene Complexes Analogous to Grubbs-I Catalysts Featuring Germylenes as Ancillary Ligands

Reactions of the first-generation Grubbs’ catalyst trans-[RuCl2(CHPh)(PCy3)2] (1) with the amidinatogermylenes Ge(tBu2bzam)R (R = tBu (L1), CH2SiMe3 (L2); tBu2bzam = N,N′-bis(tertbutyl)benzamidinate) have allowed the isolation and full characterization of the first specimens of Grubbs-type carbene complexes featuring heavier tetrylenes as ancillary ligands, namely, the disubstituted derivatives trans-[RuCl2(CHPh)(L1)2] (3) and cis-[RuCl2(CHPh)(L2)2] (7), which curiously differ in the arrangement of their germylene ligands. DFT calculations have revealed that the different volumes of L1 and L2 (the former is larger than the latter) are responsible for the different stereochemistry of 3 and 7. NMR-monitoring of the reaction solutions has allowed the observation of the monosubstituted intermediates trans-[RuCl2(CHPh)(L)(PCy3)] (L = L1 (2), L2 (5)) and their evolution to either the disubstituted final product (for L1) trans-[RuCl2(CHPh)(L1)2] (3) or the short-lived disubstituted intermediate (for L2) trans-[RuCl2(CHPh)(L2)2] (6). Complex 7 arises from a trans-to-cis isomerization of intermediate 6. As olefin metathesis catalysts, both 3 and 7 promoted the ring-closing metathesis of diethyl 2,2-diallylmalonate and the ring-opening metathesis polymerization of norbornene, but their catalytic activity decreased with the reaction time, indicating catalyst decomposition.

Functional Metathesis Catalyst Through Ring Closing Enyne Metathesis: One Pot Protocol for Living Heterotelechelic Polymers.

Enyne ring closing metathesis has been used to synthesize functional group carrying metathesis catalysts from a commercial (Ru-benzylidene) Grubbs' catalysts. The new Grubbs-type ruthenium carbene was used to synthesize living heterotelechelic ROMP polymers without any intermediate purification. Olefin metathesis with a mono substituted alkyne followed by ring closing metathesis with an allylic ether provided efficient access to new functional group carrying metathesis catalysts. Different functional benzylidene and alkylidene derivatives have been investigated in the synthesis of heterotelechelic polymers in one pot.

Half-Sandwich Ruthenium Carbene Complexes Link trans-Hydrogenation and gem-Hydrogenation of Internal Alkynes.

The hydrogenation of internal alkynes with [Cp*Ru]-based catalysts is distinguished by an unorthodox stereochemical course in that E-alkenes are formed by trans-delivery of the two H atoms of H2. A combined experimental and computational study now provides a comprehensive mechanistic picture: a metallacyclopropene (η2-vinyl complex) is primarily formed, which either evolves into the E-alkene via a concerted process or reacts to give a half-sandwich ruthenium carbene; in this case, one of the C atoms of the starting alkyne is converted into a methylene group. This transformation represents a formal gem-hydrogenation of a π-bond, which has hardly any precedent. The barriers for trans-hydrogenation and gem-hydrogenation are similar: whereas DFT predicts a preference for trans-hydrogenation, CCSD(T) finds gem-hydrogenation slightly more facile. The carbene, once formed, will bind a second H2 molecule and evolve to the desired E-alkene, a positional alkene isomer or the corresponding alkane; this associative pathway explains why double bond isomerization and over-reduction compete with trans-hydrogenation. The computed scenario concurs with para-hydrogen-induced polarization transfer (PHIP) NMR data, which confirm direct trans-delivery of H2, the formation of carbene intermediates by gem-hydrogenation, and their evolution into product and side products alike. Propargylic -OR (R = H, Me) groups exert a strong directing and stabilizing effect, such that several carbene intermediates could be isolated and characterized by X-ray diffraction. The gathered information spurred significant preparative advances: specifically, highly selective trans-hydrogenations of propargylic alcohols are reported, which are compatible with many other reducible functional groups. Moreover, the ability to generate metal carbenes by gem-hydrogenation paved the way for noncanonical hydrogenative cyclopropanations, ring expansions, and cycloadditions.