Rational Design and Evaluation of Upgraded Grubbs/Hoveyda Olefin Metathesis Catalysts: Polyfunctional Benzylidene Ethers on the Test Bench

Ginzburg Y., Anaby A., Vidavsky Y., Diesendruck C.E., Ben-Asuly A., Goldberg I., Lemcoff N.G.

The synthesis of novel sulfur-chelated ruthenium benzylidenes afforded latent catalysts with a wider range of activities and new isomeric forms. A ruthenium complex with a tridentate ligand displayed latency for even one of the most reactive ROMP monomers, dicyclopentadiene, while a room temperature latent trifluoromethyl-substituted thioether derivative was shown to be the most active sulfur-chelated precatalyst to date in several metathesis reactions at higher temperatures. These new complexes widen the spectrum of activity for this family of catalysts, enabling several practical applications and enhancing the understanding for the mechanisms of activation in strongly chelated ruthenium alkylidenes.

Costabile C., Mariconda A., Cavallo L., Longo P., Bertolasi V., Ragone F., Grisi F.

The synthesis of Ru-based precatalysts with N-heterocyclic carbene (NHC) ligands bearing syn- and anti-methyl groups on the NHC backbone and aryl N-substituents with differing steric bulk was carried out. The catalytic behavior of the monophospine Ru precatalysts (7a, 7b, 8a, and 8b) was compared to the corresponding family of phosphine-free catalysts (9a, 9b, 10a and 10b) in the ring-closing metathesis (RCM) of olefins. These catalysts showed high efficiency in RCM reactions and the syn-isomers 7a and 9a, in particular, proved to be among the most active catalysts in the formation of tetrasubstituted olefins through RCM. DFT studies on the entire RCM catalytic cycle of hindered olefins were performed to rationalize the different behaviors of catalysts with syn- and anti-methyl groups on the NHC backbone. Theoretical results not only disclosed how NHC symmetry influences the overall activity of the catalyst, but also gave relevant and more general indications on the crucial steps of the RCM of olefins.

Keitz B.K., Bouffard J., Bertrand G., Grubbs R.H.

The synthesis of a ruthenium complex containing an N-heterocylic carbene (NHC) and a mesoionic carbene (MIC) is described wherein addition of a Brønsted acid results in protonolysis of the Ru-MIC bond to generate an extremely active metathesis catalyst. Mechanistic studies implicated a rate-determining protonation step in the generation of the metathesis-active species. The activity of the NHC/MIC catalyst was found to exceed those of current commercial ruthenium catalysts.

Endo K., Grubbs R.H.

We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands that catalyze highly Z-selective olefin metathesis. A very simple and convenient procedure for the synthesis of such catalysts has been developed. Intramolecular C-H bond activation of the NHC ligand, promoted by anion ligand substitution, forms the appropriate chelate for stereocontrolled olefin metathesis.

Moerdyk J.P., Bielawski C.W.

A series of Ru-based olefin metathesis catalysts containing N,N′-diamidocarbenes (DACs) were synthesized and studied. X-ray crystallographic analysis revealed that the Ru−Ccarbene distances (1.938(5)−1.984(4) A) measured in the DAC-supported complexes were relatively short, particularly in comparison to the range of Ru−Ccarbene distances typically observed in analogous N-heterocyclic carbene (NHC) supported complexes (1.96−2.03 A). While the Tolman electronic parameters (TEP) of various DACs (2056−2057 cm−1) were calculated to be similar to that of PCy3 (2056 cm−1), the ring-closing metathesis (RCM) of diethyl diallylmalonate facilitated by DAC-supported Ru complexes proceeded at a relatively slow rate. However, unlike the phosphine-containing complexes, the DAC analogues catalyzed the RCM of diethyl dimethallylmalonate to its respective tetrasubstituted olefin. A series of electrochemical experiments revealed that the Ru complexes bearing a DAC ligand underwent oxidation at significantly higher potential...

Urbina-Blanco C.A., Leitgeb A., Slugovc C., Bantreil X., Clavier H., Slawin A.M., Nolan S.P.

The synthesis and characterization of two new ruthenium indenylidene complexes [RuCl(2)(SIPr)(Py)(Ind)] 6 and [RuCl(2)(SIPr)(3-BrPy)(Ind)] 7 featuring the sterically demanding N-heterocyclic carbene 1,3-bis(2,6-di isopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) are reported. Remarkable activity was observed with these complexes in ring closing, enyne, and cross metathesis of olefins at low catalyst loadings. The performance of SIPr-bearing complexes 6 and 7 as well as [RuCl(2)(SIPr)(PCy(3))(Ind)] 5 in ring opening metathesis polymerization is also disclosed. This work highlights the enormous influence of the neutral "spectator" ligands on catalyst activity and stability.

Magano J., Dunetz J.R.

Barrell M.J., Campaña A.G., von Delius M., Geertsema E.M., Leigh D.A.

Wang D., Wurst K., Buchmeiser M.R.

Vorfalt T., Wannowius K.J., Thiel V., Plenio H.

Peeck L.H., Leuthäusser S., Plenio H.

Grubbs−Hoveyda and Grubbs III type complexes with ferrocenyl- or −NEt2-substituted NHC ligands were synthesized according to standard procedures. The electron donation of the NHC ligands in the respective ruthenium complexes can be modulated by oxidation of the ferrocenyl moiety or by protonation of the amino group. The neutral and the respective cationic (oxidized or protonated) ruthenium complexes were tested in the ROMP of norbornene. The change in the electron donation of the NHC ligands upon protonation leads to a significant change in the double-bond geometry (from E/Z ratio = 0.78 to E/Z = 1.04) and in the microstructure of the resulting polynorbornene. Consequently, addition of acid and protonation of the living catalyst attached to the polymer chain during the polymerization reaction allows fine-tuning the E/Z ratio of the resulting polynorbornene.

Vorfalt T., Wannowius K., Plenio H.

Tzur E., Szadkowska A., Ben-Asuly A., Makal A., Goldberg I., Woźniak K., Grela K., Lemcoff N. .

A short overview on the structural design of the Hoveyda-Grubbs-type ruthenium initiators chelated through oxygen, nitrogen or sulfur atoms is presented. Our aim was to compare and contrast O-, N- and S-chelated ruthenium complexes to better understand the impact of electron-withdrawing and -donating substituents on the geometry and activity of the ruthenium complexes and to gain further insight into the trans-cis isomerisation process of the S-chelated complexes. To evaluate the different effects of chelating heteroatoms and to probe electronic effects on sulfur- and nitrogen-chelated latent catalysts, we synthesised a series of novel complexes. These catalysts were compared against two well-known oxygen-chelated initiators and a sulfoxide-chelated complex. The structures of the new complexes have been determined by single-crystal X-ray diffraction and analysed to search for correlations between the structural features and activity. The replacement of the oxygen-chelating atom by a sulfur or nitrogen atom resulted in catalysts that were inert at room temperature for typical ring-closing metathesis (RCM) and cross-metathesis reactions and showed catalytic activity only at higher temperatures. Furthermore, one nitrogen-chelated initiator demonstrated thermo-switchable behaviour in RCM reactions, similar to its sulfur-chelated counterparts.

Bantreil X., Randall R.A., Slawin A.M., Nolan S.P.

The synthesis of ruthenium indenylidene complexes containing mixed N-heterocyclic carbene ligands featuring one sterically small NHC [IMeMe (1,3,4,5-tetramethylimidazol-2-ylidene), IiPrMe (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene), and ICy (1,3-dicyclohexylimidazol-2-ylidene)] and one larger congener SIMes (1,3-bis-(2,4,6 trimethylphenyl)imidazolin-2-ylidene) is described. Characterization by X-ray diffraction allowed for calculation of percent buried volume of the small NHCs in these complexes and for speculation on the relationship NHC/catalytic activity. In addition, these complexes displayed an enhanced stability but also a high ability to promote ring-closing metathesis reactions at catalyst loadings as low as 0.05 mol %.

Torker S., Müller A., Sigrist R., Chen P.

We have recently published a mechanistic concept for the olefin metathesis reaction with ruthenium catalysts that explains the independent control of chemo- and stereoselectivity by substitution in two orthogonal planes. The basic structure from which we started the structural modifications for improved stereoselectivity had been optimized substantially for chemoselectivity, as compared to the prototype that had been published. We designed the catalyst according to a concept in which the factor that governs alternation is directly related to the size difference of the substituents on the bidentate phosphine/phenolate ligand 2a−e and in which the origin of chemoselectivity arises from diastereomeric site control. The most selective catalyst (11d) outperforms our prototype (3) in selectivity as well as reactivity. Synthetic problems, i.e., the undesired formation of 2:1-complexes (bidentate ligand-to-ruthenium ratio) (8) by reaction of the bidentate phosphine/phenolate ligands 2a and 2b with the first-generation Hoveyda−Grubbs catalyst 4, were solved by introduction of a larger carbene unit, which not only favors the formation of 1:1-complexes but also results in increased initiation rates. The work is supported by NMR data and X-ray crystallography, which give insights into the steric properties of the investigated system.

Matveeva M., Trzaskowski B., Kajetanowicz A.

Novel Z-stereoretentive metathesis catalysts with enhanced stability and outstanding stereoselectivity are reported. They demonstrate a broad substrate scope and diverse applications, offering new possibilities for advanced synthetic transformations.

Antonova Alexandra S., Zubkov Fedor I.

Catalytic olefin metathesis using Hoveyda-Grubbs type ruthenium complexes is a powerful tool for creating complex molecules possessing a variety of practically useful properties. This method is also applied for obtaining modern polymer materials from low-demand petroleum products. Among all ruthenium complexes containing five- or six-membered chelate rings, the commercially available HG-II catalyst is the most common. In addition, other Hoveyda-Grubbs type complexes, which include a Het→Ru donor–acceptor bond in the chelate ring, often exhibit metathesis activity equal to or superior to that of HG-II. This review considers second-generation N-heterocyclic ruthenium carbene Hoveyda-Grubbs type complexes with donor–acceptor bonds such as O→Ru, S→Ru, Se→Ru, N→Ru, P→Ru and Hal→Ru in the chelate ring. Methods of preparation, analysis of stability and catalytic activity of such complexes are compared, and examples of the application of these organometallic ruthenium derivatives in the synthesis of practically relevant products are provided. The literature from 2010 to 2023 is summarized, making this review useful for a broad audience of chemists working in heterocyclic and organometallic chemistry, as well as practitioners involved in the production of catalysts and polymers.The bibliography includes 174 references.

Kinugawa T., Matsuo T.

For regulating olefin metathesis (OM) activities of Hoveyda–Grubbs second-generation complex (HG-II), the structural modification of the benzylidene ligand is a useful strategy. This paper reports the effect of a chalcogen...

Wang K., Gladysz J.A.

Nadirova M., Zieliński A., Malinska M., Kajetanowicz A.

Two new ruthenium complexes with chelating-ether benzylidene ligands bearing a furan moiety were synthesized and characterized, including X-ray crystallography. They initiated fast, also at 0 °C, and were found to be highly active in a variety of ring-closing, ene-yne, and cross-metathesis reactions, including an active pharmaceutical ingredient (API) model, which makes them good candidates for the transformation of complex polyfunctional compounds that require mild reaction conditions.

Grela K., Kajetanowicz A., Szadkowska A., Czaban‐Jóźwiak J.

This chapter describes olefin cross‐metathesis (CM) reactions catalyzed by ruthenium, molybdenum, and tungsten complexes and surveys the literature from 1993 through 2020. Cross‐metathesis has been applied to the synthesis of a wide range of functionalized alkenes, including natural and biologically active products. Due to its simplicity and inherit atom economy, CM has found applications in the preparation of fine chemicals and various building blocks, and in transformations of biomass. Tandem reactions involving CM as the key step are also reviewed. Examples discussed in this chapter serve to illustrate how the reactivity of alkene substrates in CM depends on the presence of functional groups and steric congestion in the proximity of the reacting double bonds. A discussion of the mechanism of olefin metathesis is also included.

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.

Matsuo T.

Matsuo T.

Hoveyda–Grubbs-type complexes, ruthenium catalysts for olefin metathesis, have gained increased interest as a research target in the interdisciplinary research fields of chemistry and biology because of their high functional group selectivity in olefin metathesis reactions and stabilities in aqueous media. This review article introduces the application of designed Hoveyda–Grubbs-type complexes for bio-relevant studies including the construction of hybrid olefin metathesis biocatalysts and the development of in-vivo olefin metathesis reactions. As a noticeable issue in the employment of Hoveyda–Grubbs-type complexes in aqueous media, the influence of water on the catalytic activities of the complexes and strategies to overcome the problems resulting from the water effects are also discussed. In connection to the structural effects of protein structures on the reactivities of Hoveyda–Grubbs-type complexes included in the protein, the regulation of metathesis activities through second-coordination sphere effect is presented, demonstrating that the reactivities of Hoveyda–Grubbs-type complexes are controllable by the structural modification of the complexes at outer-sphere parts. Finally, as a new-type reaction based on the ruthenium-olefin specific interaction, a recent finding on the ruthenium complex transfer reaction between Hoveyda–Grubbs-type complexes and biomolecules is introduced.

Jatmika C., Goshima K., Wakabayashi K., Akiyama N., Hirota S., Matsuo T.

The reactivities of Hoveyda–Grubbs-type complexes are tunable through second-coordination sphere effects caused by a functional group in the ligand.

Pieczykolan M., Czaban-Jóźwiak J., Malinska M., Woźniak K., Dorta R., Rybicka A., Kajetanowicz A., Grela K.

A set of nitro-activated ruthenium-based Hoveyda-Grubbs type olefin metathesis catalysts bearing sterically modified N-hetero-cyclic carbene (NHC) ligands have been obtained, characterised and studied in a set of model metathesis reactions. It was found that catalysts bearing standard SIMes and SIPr ligands (4a and 4b) gave the best results in metathesis of substrates with more accessible C–C double bonds. At the same time, catalysts bearing engineered naphthyl-substituted NHC ligands (4d–e) exhibited high activity towards formation of tetrasubstituted C–C double bonds, the reaction which was traditionally Achilles’ heel of the nitro-activated Hoveyda–Grubbs catalyst.

Alvelos H., Teixeira L., Ramos A.L., Xambre A.R.

Sensory analysis is an area of the food industry to evaluate products' organoleptic characteristics. It encompasses a tasting process that produces large amounts of data used both in decisions about the products and to evaluate the tasters. In this context, some tools that usually support Industrial Engineering processes, can help making more reliable and timely decisions. The aim of this work is then to present a decision support system – SysSensory – developed to help food companies' deal with that data, by means of collecting, processing and visualizing it. Therefore, some statistical techniques incorporated in the system are explained, the specification of the system is described and some of the system's user interfaces are presented. SysSensory is considered a valuable contribute for researchers on Sensory Analysis, Statistics, as well as Information Technologies, and also for the food industry, for which it can be an innovative tool.

Mukherjee N., Marczyk A., Szczepaniak G., Sytniczuk A., Kajetanowicz A., Grela K.

Mechanochemical synthesis of nine contemporary ruthenium catalysts used for olefin metathesis is described, being the first reported example of formation of Ru carbene organometallic complexes in solid state. Three key organometallic transformations commonly used in the synthesis of the second and third generations of Ru catalysts in solution—phosphine ligand (PCy3) exchange with in situ formed N‐heterocyclic carbene (NHC) ligand, PCy3 to pyridine ligand replacement, and benzylidene ligands interchange—were proved to work under mechanochemical conditions, affording the targets in high purity. Mechanochemical approach not only requires less amounts of organic solvent (null for synthesis, only for purification) and is scalable, but also allows for transformations that were reported impossible in the solution phase.

Pollini J., Pankau W.M., Gooßen L.J.

Isomerizing olefin metathesis is currently undergoing a transformation from laboratory curiosity to powerful synthetic concept at the heart of orthogonal tandem catalysis. In this process, an isomerization catalyst continuously moves double bonds along carbon chains, while a metathesis catalyst scrambles the residues at the C-C double bonds. This cooperative action of two catalysts can be used to access single, defined products from a complex mixture of compounds. Alternatively, it enables the transformation of uniform starting materials into complex product blends with defined, tunable properties. This concept article highlights recent developments and potential applications of this fascinating reaction concept.

Gu Y., Lin Y., Zheng J., Ye L., Wang S., Li S., Ma L., Cui D., Tang T.

Controlled chain scissions of diene-based polymers, including cis-1,4-polybutadiene (cPB), cis-1,4-polyisoprene (cPIP), trans-1,4-polyisoprene (tPIP), 1,4-polychloroprene (PCP) and polycyclooctene (PCOE), were carried out under mild conditions via the hydrozirconation between C=C bonds and bis(cyclopentadienyl) zirconium hydrochloride (Cp2ZrHCl). The molecular weights (Mn) of the chain-scission products mainly depended on the loadings of Cp2ZrHCl and reaction time regardless of reaction media and temperature; however, cis/trans configuration ratio of C=C bonds in chain-scission products was influenced by reaction media, temperature and time. By means of NMR spectroscopy, chain-scission mechanism was confirmed to be β-alkyl elimination reaction. Deuterium (2H) tracing experiments showed that the hydrogenation of C=C bonds was a detrimental competing reaction to β-alkyl elimination. Furthermore, the hydrogenation was strongly influenced by steric and electronic effects around C=C bonds. However, chemical environments around C=C bonds did not affect chain-end functionalization of products, as chain-end alkylzirconium complexes generated from β-alkyl elimination were facilely quenched by electrophiles to obtain chain-end functionalized products. More importantly, under the assistance of hydrogen (H2), highly-efficient catalytic chain scission was achieved. Even more, cross-linked rubbers (such as cross-linked cPIP) could be also cleaved catalytically into soluble oligomers.