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

Sytniczuk A., Dąbrowski M., Banach Ł., Urban M., Czarnocka-Śniadała S., Milewski M., Kajetanowicz A., Grela K.

Macrocyclic lactones, ketones, and ethers can be obtained in the High-Concentration Ring-Closing Metathesis (HC-RCM) reaction in high yield and selectivity at concentrations 40 to 380 times higher than those typically used by organic chemists for similar macrocyclizations. The new method consists of using tailored ruthenium catalysts together with applying vacuum to distill off the macrocyclic product as it is formed by the metathetical backbiting of oligomers. Unlike classical RCM, no large quantities of organic solvents are used, but rather inexpensive nonvolatile diluents, such as natural or synthetic paraffin oils. Moreover, use of a protecting atmosphere or a glovebox is not needed, as the new catalysts are perfectly moisture and air stable. In addition, some other cyclic compounds previously reported as unobtainable by RCM in neat conditions, or in high dilutions even, can be formed with the help of the HC-RCM method.

Jolly P.I., Marczyk A., Małecki P., Ablialimov O., Trzybiński D., Woźniak K., Osella S., Trzaskowski B., Grela K.

The dimerization of a saturated N-heterocyclic carbene (NHC) to tricyclic piperazine in preference to the commonly observed Wanzlick dimerization is presented. Mechanistic investigations revealed that the N-fluorene substituent of the heterocycle is implicated in both ring opening of corresponding carbene dimer and tautomerization of NHC to an azomethine ylide. This has consequences for the fate of the NHC when generated from either an azolinium salt or a pentafluorophenyl adduct. The insights gained permitted the synthesis of a new indenylidene metathesis precatalyst, which exhibits exceptional selectivity and high TONS in self-metathesis of 1-octene.

Dumas A., Tarrieu R., Vives T., Roisnel T., Dorcet V., Baslé O., Mauduit M.

A ruthenium catalyst for Z-selective olefin metathesis has been synthesized from a readily accessible N-heterocyclic carbene (NHC) ligand that is prepared using an efficient, practical, and scalable multicomponent synthesis. The desired ruthenium complex with cyclometalated NHC ligand is obtained by means of selective C(sp3)-H activation at the adamantyl fragment and X-ray diffraction analysis unambiguously confirmed the structure of the precatalyst. The catalyst demonstrated attractive catalytic performance in self- and cross-metathesis at low catalyst loading to afford the desired internal olefins with high conversion and very high Z-selectivity (up to >99%). The versatility of the chelated catalyst is illustrated by the high cis-selectivity (up to >98%) and high tacticity control (up to >98% syndiotactic) achieved in ring-opening polymerization, allowing for the production of highly microstructurally controlled norbornene-, norbornadiene-, and cyclopropene-derived polymers.

Bailey G.A., Lummiss J.A., Foscato M., Occhipinti G., McDonald R., Jensen V.R., Fogg D.E.

Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Major products, in addition to propenes, are base·HCl and olefin-bound, cyclometalated dimers [RuCl(κ2-H2IMes-H)(H2C═CHR)]2 Ru-3. These are generated in ca. 90% yield on metathesis of methyl acrylate, styrene, or ethylene in the presence of either DBU, or enolates formed by nucleophilic attack of PCy3 on methyl acrylate. They also form, in lower proportions, on metathesis in the presence of the weaker base NEt3. Labeling studies reveal that the initial site of catalyst deprotonation is not the H2IMes ligand, as the cyclometalated structure of Ru-3 might suggest, but the metallacyclobutane (MCB) ring. Computational analysis supports the unexpected acidity of the MCB protons, even for the unsubstituted ring, and by implication, its overlooked role in decomposition of Ru metathesis catalysts.

Paradiso V., Bertolasi V., Costabile C., Caruso T., Dąbrowski M., Grela K., Grisi F.

A series of Hoveyda–Grubbs second-generation catalysts containing N-alkyl/N′-aryl N-heterocyclic carbene (NHC) ligands were synthesized and investigated in representative olefin metathesis reactions. Steric perturbations of unsymmetrical NHCs were achieved through modulation of the hindrance of alkyl (neopentyl, neophyl, cyclohexyl) and aryl (2-isopropylphenyl, mesityl) substituents at the nitrogen atoms in combination with different backbone configurations (syn and anti). The NHC substitution patterns strongly influence the stability and reactivity of the corresponding complexes. In general, complexes bearing an anti NHC backbone are more stable and more active than their corresponding syn isomers. In both the series, the presence of bulky, highly branched N-alkyl groups tends to give reduced catalytic differences between syn and anti isomers, whereas the nature of the N′-aryl substituent (2-isopropylphenyl or mesityl) gives rise to different activity and/or selectivity. Of note, an N′-mesityl catalyst w...

Grudzień K., Trzaskowski B., Smoleń M., Gajda R., Woźniak K., Grela K.

N-Phenylpyrrole-2,6-diisopropylphenyl ruthenium complex and its perbrominated derivative are active in ring-closing metathesis at 80 °C, but inactive at room temperature.

Małecki P., Gajda K., Ablialimov O., Malińska M., Gajda R., Woźniak K., Kajetanowicz A., Grela K.

In our search for more-selective olefin metathesis catalysts, a series of Hoveyda–Grubbs-type second-generation complexes bearing unsymmetrical N-heterocyclic carbene (NHC) ligands were synthesized and tested in model reactions. It was found that the N-benzyl substituent in NHC has a positive influence on the selectivity of the newly obtained catalysts in the self-metathesis reaction of α-olefins. As expected, a typical relationship between activity and selectivity with respect to the N-aryl substituent used was observed. Dipp-containing complexes exhibited higher stability at elevated temperature, while Mes-bearing complexes typically gave better yields than their Dipp analogues.

Kajetanowicz A., Milewski M., Rogińska J., Gajda R., Woźniak K.

Three new quinone-containing Hoveyda-type complexes have been synthesised and fully characterised. Their ability to suppress undesired double-bond migration along the carbon chain during metathesis reactions was examined. It was proved that these catalysts decrease the amounts of undesired side-products with a shifted double bond in the reaction mixture.

Gawin R., Kozakiewicz A., Guńka P.A., Dąbrowski P., Skowerski K.

The state-of-the-art in olefin metathesis is application of N-heterocyclic carbene (NHC)-containing ruthenium alkylidenes for the formation of internal C=C bonds and of cyclic alkyl amino carbene (CAAC)-containing ruthenium benzylidenes in the production of terminal olefins. A straightforward synthesis of bis(CAAC)Ru indenylidene complexes, which are highly effective in the formation of both terminal and internal C=C bonds at loadings as low as 1 ppm, is now reported.

Gawin R., Kozakiewicz A., Guńka P.A., Dąbrowski P., Skowerski K.

Rouen M., Queval P., Borré E., Falivene L., Poater A., Berthod M., Hugues F., Cavallo L., Baslé O., Olivier-Bourbigou H., Mauduit M.

The search for a low-cost process for the valorization of linear α-olefins combining high productivity and high selectivity is a longstanding goal for chemists. Herein, we report a soluble ruthenium olefin metathesis catalyst that performs the conversion of linear α-olefins to longer internal linear olefins with high selectivity (>99%) under neat conditions at low loadings (50 ppm) and without the need of expensive additives. This robust catalytic process allowed us to efficiently and selectively re-equilibrate the naphtha fraction (C5–C8) of a Fischer–Tropsch feed derived from non-petroleum resources to a higher-value product range (C9–C14), useful as detergent and plasticizer precursors.

Luo S., Cannon J.S., Taylor B.L., Engle K.M., Houk K.N., Grubbs R.H.

Olefin metathesis reactions with 3E-1,3-dienes using Z-selective cyclometalated ruthenium benzylidene catalysts are described. In particular, a procedure for employing 3E-1,3-dienes in Z-selective homodimerization and cross-metathesis with terminal alkenes is detailed. The reaction takes advantage of the pronounced chemoselectivity of a recently reported ruthenium-based catalyst containing a cyclometalated NHC ligand for terminal alkenes in the presence of internal E-alkenes. A wide array of commonly encountered functional groups can be tolerated, and only a small excess (1.5 equiv) of the diene coupling partner is required to achieve high yields of the desired internal E,Z-diene cross-metathesis product. Computational studies have been performed to elucidate the reaction mechanism. The computations are consistent with a diene-first pathway. The reaction can be used to quickly assemble structurally complex targets. The power of this cross-metathesis reaction is demonstrated by the concise syntheses of two insect pheromones.

Smoleń M., Kośnik W., Loska R., Gajda R., Malińska M., Woźniak K., Grela K.

New ruthenium(ii) indenylidene catalysts were synthesized and used in olefin metathesis reactions in toluene under air, leading to high conversions and good selectivities.

Higman C.S., Lanterna A.E., Marin M.L., Scaiano J.C., Fogg D.E.

The second-generation Grubbs catalyst, RuCl2(H2IMes)(PCy3) (=CHPh) [GII; H2IMes=1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene, Cy=cyclohexyl], is shown to decompose during olefin metathesis to generate Ru nanoparticles (RuNPs). These RuNPs appear to contribute significantly to competing isomerization during metathesis. Larger, partially oxidized RuNPs are also observed in commercial GII, but these exhibit modest isomerization activity. Removal of RuNPs from the precatalyst does not prevent isomerization, because new, more reactive NPs are generated by catalyst decomposition during metathesis.

Engl P.S., Fedorov A., Copéret C., Togni A.

We report the synthesis of ruthenium metathesis catalysts containing unsymmetrical N-trifluoromethyl NHC ligands. These complexes have been fully characterized, and a Ru–F interaction has been identified in the solid state by X-ray crystallographic analysis for three catalysts with Ru–F distances between 2.629(2) and 2.652(2) A. The influence of the N-trifluoromethyl NHC ligands on the initiation rates and activation parameters was studied. The activity of these catalysts was evaluated in benchmark olefin metathesis reactions and compared to the standard second-generation Grubbs catalyst. Remarkably, N-trifluoromethyl catalysts display an unusually high selectivity for the formation of terminal olefins (up to 90%) in the ethenolysis of ethyl oleate. Much improved selectivity is demonstrated for alternating copolymerization of cyclooctene and norbornene as well. These results underline the importance of electronic effects exerted by the NHC ligand.

Langellotti V., Melchiorre M., Cucciolito M.E., Esposito R., Ruffo F.

AbstractCatalysis is a green methodology aimed at optimizing synthetic procedures by simplifying the design of target molecules and reducing energy and material consumption. However, catalytic reactions often rely on polar aprotic solvents, such as dimethylformamide (DMF) or acetonitrile, which present environmental and health issues. In response, manufacturers and researchers are exploring greener alternatives derived from residual biomass, which reduce the negative environmental impact of traditional solvents. These new classes of solvents are termed ‘neoteric’ in order to distinguish them from traditional solvents with well-established applications. This graphical review highlights key findings on the use of these new solvents in metal-catalyzed coupling reactions.

Zhan J., Chen J., Wei L., Cai M.

AbstractA novel, highly efficient heterogeneous palladium‐catalyzed carbonylative cyclization of aryl iodides and benzyl acetylenes has been developed under an atmospheric pressure of CO. The reaction proceeds smoothly in a bioderived solvent 2‐methyltetrahydrofuran (2‐MeTHF) at 50 °C using an MCM‐41‐anchored bidentate phosphine palladium complex [Pd(OAc)2‐MCM‐41‐P,P] as catalyst with DiPEA as base, delivering a wide variety of 3‐alkylidenefuran‐2‐ones in good to excellent yields. The Pd(OAc)2‐MCM‐41‐P,P complex can be easily recovered by a simple centrifugation and recycled more than ten times without any remarkable loss of catalytic activity. The present method not only avoids the use of toxic solvents such as benzene, toluene and THF, but also addresses the key problem of expensive palladium catalyst recovery and recycle, thus preventing palladium contamination in the final product.

Martínez J.P., Trzaskowski B.

Liu T., Wang L., Wu K., Wang Q., Yu Z.

Various pincer-type ruthenium(II) complexes were developed from our laboratories and herein the relevant advance is summarized from a viewpoint of their synthesis and organic synthetic applications as homogeneous catalysts. The investigated Ru(II)-NNN and Ru(II)-NNNN-type complexes exhibited highly catalytic activities in the transfer hydrogenation of ketones, C-C bond formation from alcohols and ketones, and dehydrogenation. RuH complexes were identified or considered as the catalytically active intermediates for these transformations. This review deals with the following subjects: (i) mononuclear ruthenium(II) pincer complexes with high catalytic activity in (asymmetric) transfer hydrogenation of ketones; (ii) multinuclear ruthenium(II) complexes for transfer hydrogenation of ketones; (iii) mononuclear ruthenium(II) complexes for other reactions such as Oppenauer-type oxidation, β-alkylation of secondary alcohols, synthesis of multisubstituted heterocycles, acceptorless dehydrogenation of N-heterocycles and secondary alcohols.

Nadirova M., Cejas-Sánchez J., Sebastián R.M., Wiszniewski M., Chmielewski M.J., Kajetanowicz A., Grela K.

Two new unsymmetrical N-heterocyclic carbene ligand (uNHC)-based ruthenium complexes featuring phenolic OH function were obtained and fully characterised. The more active one was then immobilised on the metal–organic framework (MOF) solid support (Al)MIL-101-NH2. The catalytic activity of such a heterogeneous system was tested, showing that, while the heterogeneous catalyst is less active than the corresponding homogeneous catalyst in solution, it can catalyse selected olefin metathesis reactions, serving as the proof-of-concept for the immobilisation of catalytically active complexes in MOFs using a phenolic tag.

Kovács E., Balterer B., Anh Duc N., Szarka G., Owen M.C., Domján A., Iván B.

A tremendous number of solvents, either as liquids or vapors, contaminate the environment on a daily basis worldwide. Olefin metathesis, which has been widely used as high-yielding protocols for ring-opening metathesis polymerization (ROMP), ring-closing metathesis (RCM), and isomerization reactions, is typically performed in toxic and volatile solvents such as dichloromethane. In this study, the results of our systematic experiments with the Grubbs G1, G2, and Hoveyda-Grubbs HG2 catalysts proved that benzotrifluoride (BTF) can replace dichloromethane (DCM) in these reactions, providing high yields and similar or even higher reaction rates in certain cases. The ROMP of norbornene resulted not only in high yields but also in polynorbornenes with a high molecular weight at low catalyst loadings. Ring-closing metathesis (RCM) experiments proved that, with the exception of the G1 catalyst, RCM occurs with similar high efficiencies in BTF as in DCM. It was found that isomerization of (Z)-but-2-ene-1,4-diyl diacetate with the G2 and HG2 catalysts proceeds at significantly higher initial rates in BTF than in DCM, leading to rapid isomerization with high yields in a short time. Overall, BTF is a suitable solvent for olefin metathesis, such as polymer syntheses by ROMP and the ring-closing and isomerization reactions.

Grzesiński Ł., Milewski M., Nadirova M., Kajetanowicz A., Grela K.

Yu B., Hamad F.B., Van Hecke K., Verpoort F.

We report on the synthesis and characterization of new ruthenium indenylidene complexes bearing two unsymmetrical N-heterocyclic carbene (NHC) ligands denoted as RuCl2(3-phenyl-1-indenylidene)bis(1-mesityl-3-R-4,5-dihydroimidazole-2-ylidene) in which R is methyl 7a and cyclohexyl 7b. Complexes 7a and 7b were analyzed using single-crystal X-ray diffraction analysis, elemental analysis, IR, NMR spectroscopy, and HRMS. The catalytic activities of complexes 7a and 7b were evaluated in olefin metathesis reactions: ring-opening metathesis polymerization (ROMP) of cis,cis-1,5-cyclooctadiene (COD) and ringclosing metathesis (RCM) of diethyl diallyl malonate (DEDAM) as well as in the isomerization of allylic alcohols. Complexes 7a and 7b failed to initiate the reactions at room temperature in all tested reactions, which might be due to the high thermal stability and low degree of lability of the Ru-CNHC bonds. At 80 °C, the complex 7a showed the best performance due to an increased initiation and a decreased steric obstruction towards the incoming substrates.

Liu Y., Voloshkin V.A., Scattolin T., Peng M., Van Hecke K., Nolan S.P., Cazin C.S.

A novel family of air- and moisture-stable trans-[Pd(NHC)Cl2(DMS/THT)] was synthesized using a simple and eco-friendly synthetic protocol. These catalysts displayed outstanding performance in Buchwald-Hartwig and Suzuki-Miyaura reaction in green solvents.

Liu Y., Scattolin T., Gobbo A., Beliš M., Van Hecke K., Nolan S.P., Cazin C.S.

Toh R.W., Patrzałek M., Nienałtowski T., Piątkowski J., Kajetanowicz A., Wu J., Grela K.

In recent years, the development of continuous-flow reactors has attracted growing attention from the synthetic community. Moreover, findings in the precise control of the reaction parameters and improved mass/heat transfer have made the flow setup an attractive alternative to batch reactors, both in academia and industry, enabling safe and easy scaling-up of synthetic processes. Even though a majority of the pharmaceutical industry currently rely on batch reactors or semibatch reactors, many are integrating flow technology because of easier maintenance and lower risks. Herein, we demonstrate an operationally simple flow setup for homogeneous ring-closing metathesis, which is applicable to the synthesis of active pharmaceutical ingredients precursors or analogues with high efficiency, low residence time, and in a green solvent. Furthermore, through the addition of a soluble metal scavenger in the subsequent step within the flow system, the level of ruthenium contamination in the final product can be greatly reduced (to less than 5 ppm). To ensure that this method is applicable for industrial usage, an upscale process including a 24 h continuous-flow reaction for more than 60 g of a Sildenafil analogue was achieved in a continuous-flow fashion by adjusting the tubing size and flow rate accordingly.

Rana R., Shreya, Upadhyay R., Maurya S.K.

Macrocyclic lactones have redolent characteristics of muscones that originate from the rectal musk organs of the musk deer. These lactones are the primary raw material in the flavor and fragrance industry and are also found within the cyclic frameworks of various bioactive molecules. Due to great demand, many efforts have been made for their synthesis; however, strategies generating a large number of macrocyclic analogues from renewable resources have not been fully realized and are urgently required. Here, we outline a sustainable, straightforward, and eco-friendly approach to synthesize high-valued macrocyclic lactones utilizing olive oil under greener reaction conditions. The outlined method allows us to turn biomass into valuable 12- to 29-membered lactones and dilactones.

Ma X., Guillet S.G., Liu Y., Cazin C.S., Nolan S.P.

A novel, efficient and facile protocol for the synthesis of a series of [Ru(NHC)(CO3)(p-cymene)] complexes is reported.

Monsigny L., Kajetanowicz A., Grela K.

This review describes a distinct class of ruthenium olefin metathesis catalysts featuring unsymmetrical N-heterocyclic carbene (uNHC) ligands, from its historical beginning to the present state of the art. Thanks to advantageous traits, such as pronounced thermodynamic stability, chemical latency, outstanding selectivity, and compatibility with green solvents, these catalysts led to good results in a number of specialized metathesis transformations. Therefore, while being a niche, the uNHC complexes can potentially be implemented in a number of industrial processes, such as valorization of Fischer-Tropsch olefin fractions, ethenolysis of renewable products, and modern pharmaceutical production.

Wei W., Jia G.

The coordination chemistry of ruthenium, osmium, technetium and rhenium with carbon-based ligands covering the literature from 2003 to 2018 is discussed. These metals form a vast number of coordination compounds with carbon-based ligands ranging from a single carbon atom (a carbido ligand) to polydentate hydrocarbon chains, and from monodentate organometallic ligands such as carbenes to multidentate ligands such as pincers and macrocycles. Particular focus of this review is given to syntheses, properties and applications of complexes with popular carbon-based ligands such as monodentate N-heterocyclic carbenes (NHCs), cyclometallated bidentate ligands, tridentate pincers and porphyrin-like macrocycles.