Ruthenium Carbene Research Articles

A stable ruthenium complex bearing a 1,2-dicarbadodecaborane(12)-1,2-dithiolate ligand and its activation for olefin metathesis

In this article, a new ruthenium carbene catalyst containing a N-heterocyclic carbene, a pyridine-appended benzylidene carbene, and a 1,2-dicarbadodecab- orane(12)-1,2-dithiolate ligand was synthesized. The ruthenium complex is very stable in air or in solution owing to the large steric hindrance and strong coordination effect of the ligands. The ruthenium complex is almost inert for olefin metathesis reactions. When combined with a Lewis acid or a p-toluene sulfonic acid, the ruthenium complex could catalyze the cross metathesis reactions of terminal alkenes and (Z)-but-2-ene-1,4-diol to give high yields of desired products. The E-products were obtained predominantly in these reactions. Similar to other ruthenium-based catalysts, this new ruthenium complex can tolerate many different functional groups.

Retraction of “A 1,2-Dicarbadodecaborane(12)-1,2-Dithiolate Chelating Ruthenium Carbene Catalyst for Highly Z Selective Olefin Metathesis”

A highly Z selective olefin metathesis 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. Due to the large steric hindrance and strong electron-withdrawing effects of the carborane ligand, the new ruthenium complex is more stable than previously reported Ru catalysts which contain benzene-1,2-dithiolate ligands. The new ruthenium carbene catalyst can catalyze cross-metathesis (CM) reactions of terminal alkenes with (Z)-but-2-ene-1,4-diol and CM reactions of other terminal alkenes to give highly Z selective products in moderate to good yields. In addition, the catalyst was also able to catalyst a ring-closing metathesis (RCM) reaction to give a macrocyclic ring compound with a (Z)-olefin structure as the major product. Like other ruthenium carbene catalysts, the new complex tolerates many different functional groups.

Novel olefin metathetis catalysts with fluorinated N-alkyl-N´-arylimidazolin-2-ylidene ligands

Novel ruthenium carbene complexes bearing unsymmetrical NHC-ligands based on N-alkyl-N´-arylimidazoline with hexafluoroisopropylmethoxy group in para-position of N-aryl moiety have been synthesized. Catalytic activity of complexes obtained was investigated on model reactions of intra- and intermolecular olefin metathesis.

Synthetic Applications of Vinyl Ruthenium Carbenes Derived from Diazoalkanes and Alkynes

AbstractRuthenium‐catalyzed C–C bond forming reactions between diazoalkanes and alkynes have gained much attention in recent years due to their unique ways for the formation of various synthetic scaffolds via an electrophilic vinyl ruthenium carbene intermediate. These 16‐electron species are isoelectronic with the Grubbs type ruthenium‐benzylidene catalyst, but their structural geometry and ligand liability make them more innovative in catalytic reactions. Recent advances in this field with respect to vinyl ruthenium carbenes and their coupling partners, thus leading to a step‐economical access to versatile molecular architectures, are discussed herein in a sustainable manner.magnified image

Cyclic Alkyl Amino Ruthenium Complexes—Efficient Catalysts for Macrocyclization and Acrylonitrile Cross Metathesis

The active species generated from ruthenium complexes bearing N-heterocyclic carbene (NHC) ligands exhibit limited stability under certain conditions (high dilution, high temperature) and in the presence of nitrile functionality. As a consequence, industrial implementation of metathesis for the production of important materials such as macrocyclic musks and polyamide 11 is uneconomical. Over the past decade, hundreds of ruthenium complexes bearing NHC ligands have been obtained. However, to this date, they have brought rather limited improvements in efficiency. In this paper, we report on cyclic alkyl amino carbene (CAAC) ruthenium complexes that promote highly challenging macrocyclization and cross metathesis (CM) with acrylonitrile reactions at loadings as low as 10–20 ppm.

Cooperative Bond Activation Reactions with Ruthenium Carbene Complex PhSO2(Ph2PNSiMe3)C═Ru(p-cymene): Ru═C and N–Si Bond Reactivity

The synthesis of ruthenium carbene complex PhSO2(Ph2PNSiMe3)C═Ru(p-cymene) (3) and its application in cooperative bond activation reactions were studied. Compound 3 is accessible via salt metathesis using the dilithium methandiide ligand or alternatively via dehydrohalogenation of the corresponding chlorido complex 2. The carbene complex was studied by X-ray crystallography, multielement NMR spectroscopy, and DFT studies, all of which confirm the presence of a Ru═C double bond. The polarization of the Ru═C bond is less pronounced than in an analogous carbene complex with a thiophosphoryl instead of the iminophosphoryl moiety. This should be beneficial for realizing reversible activation processes by the addition of element-hydrogen bonds across the Ru═C double bond. Accordingly, 3 is more stable and the Ru═C linkage less reactive in the activation of aromatic alcohols and elemental dihydrogen, showing reversible processes and longer reaction times. Despite the selective addition of dihydrogen across the R...

Cross-Metathesis/Intramolecular (Hetero-)Michael Addition: A Convenient Sequence for the Generation of Carbo- and Heterocycles

The high stability and functional group compatibility of ruthenium carbene complexes confer them a great ability to catalyze domino processes. For this reason, the combination of metathesis reactions with additional transformations in a domino fashion has been exploited extensively, with the result of expanding the utility of ruthenium carbene complexes beyond that of just olefin metathesis. Among those domino processes, it is worth mentioning the sequence of cross-metathesis/intramolecular Michael addition, which allows for the generation of a wide variety of carbo- and heterocycles in a very simple manner, taking advantage of the benefits of domino reactions. Carbon-, oxygen- and nitrogen-centered nucleophiles are good partners in this protocol, the versatility of which has been illustrated with the synthesis of several biologically important compounds.1 Introduction2 Cross Metathesis/Intramolecular Aza-Michael Addition Sequences3 Cross Metathesis/Intramolecular Oxa-Michael Addition Sequences4 Cross Metathesis/Intramolecular Michael Addition Sequences5 Conclusions and Outlook

Front Cover: First Detection of a Ruthenium–Carbene–Resorc[4]arene Complex During the Progress of a Metathesis Reaction (Eur. J. Org. Chem. 17/2017)

Front Cover: First Detection of a Ruthenium–Carbene–Resorc[4]arene Complex During the Progress of a Metathesis Reaction (Eur. J. Org. Chem. 17/2017)

First Detection of a Ruthenium–Carbene–Resorc[4]arene Complex During the Progress of a Metathesis Reaction

For the first time we describe the detection of a ruthenium‐carbene‐resorc[4]arene complex produced, as a key intermediate, during an olefin metathesis reaction carried out on a resorc[4]arene bicyclic olefin with [Ru(=CHPh)Cl2(PCy3)2] Grubbs first‐generation (G1ST) catalyst. The complex was identified by using high‐resolution (600 MHz) 1H, 31P NMR and DOSY spectroscopy, in a non‐invasive fashion. The singlet at δ = 19.98 ppm (1H NMR), attributed to the alkylidene proton in the G1ST catalyst and that at δ = 53.37 ppm (31P NMR), attributed to the phosphorus atom coordinated with the metal, were selected as probes for a kinetic analysis. The intensity of these signals decreased at the expense of the singlets at 19.26 (1H NMR) and 52.68 ppm (31P NMR), diagnostic for the formation of the ruthenium‐carbene‐resorc[4]arene complex 3a[Ru]. The resorc[4]arene activated olefin proved to behave as a key propagating species leading to oligomers according to a ROMP pathway.

Effects of End-Groups on Photophysical Properties of Poly(9,9-di-n-octylfluorene-2,7-vinylene)s Linked with Metalloporphyrins: Synthesis and Time-Resolved Fluorescence Spectroscopy

A series of poly(9,9-di-n-octyl-fluorene-2,7-vinylene)s (PFVs) containing metalloporphyrins at the chain ends with different conjugation lengths (ca. average 8 or 24 FV repeat units), PFV-[Por(M)]2, have been prepared by olefin metathesis of the vinyl chain ends in PFVs (prepared by acyclic diene metathesis polymerization by ruthenium–carbene catalysts) using molybdenum–alkylidene catalyst (reagent) followed by Wittig-type cleavage with formyl porphyrin containing different metal ions [Zn(II), Cu(II), Ni(II), and Pt(II)]. Effects of the metalloporphyrins on photophysical properties of PFVs were studied by means of time-resolved fluorescence spectroscopy. The fluorescence spectral profile from PFV moiety in all the polymers with end-porphyrins was almost identical to that of the reference PFV. However, fluorescence quantum yields were remarkably lower, depending upon the central metal ion and the chain length. The observed reduction of the quantum yields is ascribed to intramolecular energy transfer to the...

Enolesters as chain end‐functionalizing agents for the living ring opening metathesis polymerization

ABSTRACTFunctional enolethers have previously been used to introduce functional end groups at the chain end of ruthenium carbene complex initiated living ring opening metathesis polymers. Here, we investigated whether the weaker π‐donating enolesters could equally be used in regio selective reactions with ruthenium carbene complexes and thus as polymer end‐functionalization reagents. Enolesters such as vinyl acetate, butenyl acetate, 3‐(4‐(tert‐butoxy)phenyl)propenyl acetate and 6‐(((benzyloxy)carbonyl)amino)hex‐1‐en‐1‐yl acetate were used as living ROMP terminating agents. All gave the expected end groups proving that enolesters are synthetically easily accessible targets for living ROMP end‐functionalization. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2983–2990

Synthesis and Application of Novel Ruthenium Catalysts for High Temperature Alkene Metathesis

Four pyridinyl alcohols and the corresponding hemilabile pyridinyl alcoholato ruthenium carbene complexes of the Grubbs second generation-type RuCl(H2IMes)(O^N)(=CHPh), where O^N = 1-(2′-pyridinyl)-1,1-diphenyl methanolato, 1-(2′-pyridinyl)-1-(2′-chlorophenyl),1-phenyl methanolato, 1-(2′-pyridinyl)-1-(4′-chlorophenyl),1-phenyl methanolato and 1-(2′-pyridinyl)-1-(2′-methoxyphenyl),1-phenyl methanolato, are synthesized in very good yields. At high temperatures, the precatalysts showed high stability, selectivity and activity in 1-octene metathesis compared to the Grubbs first and second generation precatalysts. The 2-/4-chloro- and 4-methoxy-substituted pyridinyl alcoholato ligand-containing ruthenium precatalysts showed high performance in the 1-octene metathesis reaction in the range 80–110 °C. The hemilabile 4-methoxy-substituted pyridinyl alcoholato ligand improved the catalyst stability, activity and selectivity for 1-octene metathesis significantly at 110 °C.

Kinetically E-selective macrocyclic ring-closing metathesis.

Macrocyclic compounds are central to discovery of new drugs but their preparation is often challenging because of the energy barrier required for bringing together and fusing the two ends of an acyclic precursor1. Ring-closing metathesis (RCM) 2,3,4 is a catalytic process that has allowed access to countless biologically active macrocyclic organic molecules even on large scale (up to 200 kilograms)5. The potency of a macrocyclic compound can depend on the stereochemistry of its alkene, or one isomer might be needed for subsequent stereoselective modification (e.g., dihydroxylation6). Still, while kinetically controlled Z-selective RCM reactions have been reported7,8,9,10, the only available olefin metathesis approach for accessing macrocyclic E olefins entails selective removal of the Z component of a stereoisomeric mixture by ethenolysis10, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization, a particularly serious problem when the E alkene is energetically less favored. Here, we show that dienes containing an E-alkenyl–B(pinacolato) group, widely used in catalytic cross-coupling11, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E macrocyclic alkenes. Reactions are promoted by a molybdenum monoaryloxide pyrrolide complex and afford products in up to 73 percent yield and >98:2 E:Z ratio. Utility is highlighted by application to preparation of the twelve-membered ring antibiotic recifeiolide12,13 and the eighteen-membered ring Janus kinase 2/Fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor pacritinib14,15 the Z isomer of which has lower potency than the E16. The eighteen-membered ring moiety of pacritinib, a potent in vivo anti-cancer agent in advanced clinical trials for treatment of lymphoma and myelofibrosis, was prepared by an RCM carried out at 20 times higher concentration than when a ruthenium carbene was employed (0.02 vs. 0.001 M; 73% yield, 92% E).

Exploiting Ruthenium Carbene-Catalyzed Reactions in Total Synthesis of Marine Oxacyclic Natural Products

Abstract Olefin metathesis has emerged as an indispensable means to create complex natural products by the virtue of its powerful carbon–carbon bond-forming ability, compatibility with a range of functional groups, and ready availability of highly reactive ruthenium carbene catalysts. Furthermore, Grubbs-type ruthenium carbene complexes originally developed for olefin metathesis reactions also mediate a variety of non-metathetic reactions and found their use in tandem metathetic/non-metathetic processes. This account summarizes our recent efforts on total synthesis of oxacyclic natural products by means of ruthenium carbene-catalyzed reactions.

Mixed heteropentadienyl and N-heterocyclic carbene ruthenium(II) complexes: Synthesis and transfer hydrogenation catalysis

Two synthetic methodologies for obtaining novel mixed heteropentadienyl and N-heterocyclic carbenes (NHC) ruthenium(II) complexes have been explored. A synthetic strategy involving the addition of heteropentadienyl precursors to [RuII]-NHC complexes proved to be a successful route for the isolation of four novel mixed ligand complexes, namely stereoisomers [(p-cymene)RuII(BuImMe)(η3-exo-syn-CH2CHCHCHO)]BF4 (3 and 3′, BuImMe = 1-butyl-3-methylimidazolyl-2-idene) and [(η1-CH2CHCRCHSO2)RuII(PyImMe)(CH3CN)3](A) (PyImMe = 3-methyl-1-(2-pyridyl)imidazolyl-2-idene, R = H, A = BF4, 6; R = CH3, A = PF6, 7). Moreover complex 6 has been characterised by X-ray crystallography confirming the sulphur-bound monodentate nature of CH2CHCHCHSO2 ligand adopting an S-conformation. Complexes 6 and 7 were tested as pre-catalysts in the transfer hydrogenation reaction of benzophenone, showing moderate and good activities, respectively.

Synthesis and catalytic activity of supported acenaphthoimidazolylidene N-heterocyclic carbene ruthenium complex for ring closing metathesis (RCM) and ring opening metathesis polymerization (ROMP)

Ruthenium catalyzed ring closing metathesis (RCM) and ring opening metathesis polymerization (ROMP) reactions using a supported bis(arylimino)acenaphthene N-heterocyclic carbene (BIAN-NHC) complex have been reported. The BIAN-NHC Ru-complex exhibits excellent catalytic activity and tolerates a wide range of substrates at low catalyst loadings. DFT calculations were also carried out on some selected key intermediates in the reaction mechanism to study the effect of having the conjugated aromatic moiety (BIAN-NHC) in the backbone of the complex. The newly synthesized BIAN-NHC Ru-complex shows comparable catalytic activities to the commercially available second generation Ru catalyst HG2. The recycled complex was reused for up to eight reaction cycles for the RCM of N,N-diallyl tosylamine affording a high average isolated yield, with lower levels of Ru contamination in the final product.▪

Cooperative P–H Bond Activation with Ruthenium and Iridium Carbene Complexes

The reactivity of nucleophilic ruthenium and iridium carbene complexes toward the P–H bond in secondary phosphines and phosphine oxides was studied. While the reactions of the free phosphines resulted in the formation of product mixtures, the oxidized congeners gave way to fast and selective P–H bond activation reactions by means of metal–ligand cooperation and net addition of the P–H bond across the metal–carbon double bond. The formed phosphoryl complexes were characterized in the solid state and in solution, indicating C–H···O hydrogen bonding as a structural motif. Computational studies to provide insights into the reaction mechanism revealed that—in contrast to other E–H bond activation reactions with carbene complexes—no concerted 1,2-addition across the M═C bond is operative. Instead, the P–H bond activation of the phosphine oxides preferably proceeds via coordination of the phosphinous acid tautomer to the metal, followed by hydrogen transfer to the carbenic carbon atom.

Nonmetathesis Heterocycle Formation by Ruthenium-Catalyzed Intramolecular [2 + 2] Cycloaddition of Allenamide-enes to Azabicyclo[3.1.1]heptanes

We have developed a novel nonmetathesis reaction, namely, ruthenium-catalyzed intramolecular [2 + 2] cycloaddition of allenamide-enes, to give heterocycles (i.e., azabicyclo[3.1.1]heptanes). This is the first example of [2 + 2] cycloaddition using a ruthenium carbene catalyst. The reaction proceeds at room temperature, but not under thermal or radical conditions.

Enzyme‐ and Ruthenium‐Catalyzed Enantioselective Transformation of α‐Allenic Alcohols into 2,3‐Dihydrofurans

AbstractAn efficient one‐pot method for the enzyme‐ and ruthenium‐catalyzed enantioselective transformation of α‐allenic alcohols into 2,3‐dihydrofurans has been developed. The method involves an enzymatic kinetic resolution and a subsequent ruthenium‐catalyzed cycloisomerization, which provides 2,3‐dihydrofurans with excellent enantioselectivity (up to >99 % ee). A ruthenium carbene species was proposed as a key intermediate in the cycloisomerization.

Enzyme- and Ruthenium-Catalyzed Enantioselective Transformation of α-Allenic Alcohols into 2,3-Dihydrofurans.

An efficient one‐pot method for the enzyme‐ and ruthenium‐catalyzed enantioselective transformation of α‐allenic alcohols into 2,3‐dihydrofurans has been developed. The method involves an enzymatic kinetic resolution and a subsequent ruthenium‐catalyzed cycloisomerization, which provides 2,3‐dihydrofurans with excellent enantioselectivity (up to >99 % ee). A ruthenium carbene species was proposed as a key intermediate in the cycloisomerization.