22921-58-0Relevant articles and documents
Metathesis and Decomposition of Fischer Carbenes of Cyclometalated Z-Selective Ruthenium Metathesis Catalysts
Ahmed, Tonia S.,Grandner, Jessica M.,Taylor, Buck L. H.,Herbert, Myles B.,Houk,Grubbs, Robert H.
, p. 2212 - 2216 (2018)
The addition of vinyl ethers to Z-selective, cyclometalated ruthenium metathesis catalysts generates Fischer carbene complexes. Although Fischer carbenes are usually thought to be metathesis inactive, we show that Fischer carbenes are metathesis active under certain circumstances. These species were found to decompose facilely to Ru hydride complexes, as identified by both experiment and computation. Since vinyl ethers are often used to quench metathesis reactions implementing Ru-based metathesis catalysts, their decomposition to hydrides can have a deleterious effect on the desired stereochemistry of the olefin product.
Synthesis and Reactivity of Homogeneous and Heterogeneous Ruthenium-Based Metathesis Catalysts Containing Electron-Withdrawing Ligands
Krause, Jens O.,Nuyken, Oskar,Wurst, Klaus,Buchmeiser, Michael R.
, p. 777 - 784 (2004)
The synthesis and heterogenization of new Grubbs-Hoveyda type metathesis catalysts by chlorine exchange is described. Substitution of one or two chlorine ligands with trifluoroacetate and trifluoromethanesulfonate was accomplished by reaction of [RuCl2(=CH-o-iPr-O-C6H 4)(IMesH2)] (IMesH2 = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene) with the silver salts CF3COOAg and CF3SO3Ag, respectively. The resulting compounds, [Ru(CF3SO3) 2(=CH-o-iPr-O-C6H4)(IMesH2)] (1), [RuCl(CF3SO3)(=CH-o-iPr-O-C6H 4)(IMesH2)] (2), and [Ru(CF3CO 2)2(=CH-o-iPr-O-C6H4)(IMesH 2)] (3) were found to be highly active catalysts for ring-closing metathesis (RCM) at elevated temperature (45°C), exceeding known ruthenium-based catalysts in catalytic activity. Turn-over numbers (TONs) up to 1800 were achieved in RCM. Excellent yields were also achieved in enyne metathesis and ring-opening cross metathesis using norborn-5-ene and 7-oxanorborn-5-ene-derivatives. Even more important, 3 was found to be highly active in RCM at room temperature (20°C), allowing TONs up to 1400. Heterogeneous catalysts were synthesized by immobilizing [RuCl2(= CH-o-iPr-O-C6H4)(IMesH2)] on a perfluoroglutaric acid derivatized polystyrene-divinylbenzene (PS-DVB) support (silver form). The resulting supported catalyst [RuCl(polymer-CH 2-O-CO-CF2-CF2-CF 2-COO)(=CH-o-iPr-O-C6H4)(IMesH2)] (5) showed significantly reduced activities in RCM (TONs = 380) compared with the heterogeneous analogue of 3. The immobilized catalyst, [Ru(polymer-CH 2-O-CO-CF2-CF2-CF2-COO)(CF 3CO2)(=CH-o-iPr-O-C6H4)(IMesH 2)] (4) was obtained by substitution of both Cl ligands of the parent Grubbs-Hoveyda catalyst by addition of CF3COOAg to 5. Compound 4 can be prepared in high loadings (160 mg catalyst g-1 PS-DVB) and possesses excellent activity in RCM with TONs up to 1100 in stirred-batch RCM experiments. Leaching of ruthenium into the reaction mixture was unprecedentedly low, resulting in a ruthenium content -1) in the final RCM-derived products.
Ruthenabenzene: A Robust Precatalyst
Gupta, Saswata,Su, Siyuan,Zhang, Yu,Liu, Peng,Wink, Donald J.,Lee, Daesung
supporting information, p. 7490 - 7500 (2021/05/26)
Metallaaromatics constitute a unique class of aromatic compounds where one or more transition metal elements are incorporated into the aromatic system, the parent of which is metallabenzene. One of the main concerns about metallabenzenes generally deals with the structural characterization related to their relative aromaticity compared to the carbon archetype. Transition metal-containing metallabenzenes are also implicated in certain catalytic processes such as alkyne metathesis polymerization; however, these transition metal-based metallaaromatic compounds have not been developed as a catalyst. Herein, we describe an effective strategy to generate diverse arrays of ruthenabenzenes and demonstrated them as an aromatic equivalent of the Grubbs-type ruthenium alkylidene catalysts. These ruthenabenzenes can be prepared via an enyne metathesis and metallotropic [1,3]-shift cascade process to form alkyne-chelated ruthenium alkylidene intermediates followed by spontaneous cycloaromatization. The aromatic nature of these complexes was confirmed by spectroscopic and X-ray crystallographic data, and the mechanistic pathways for the cycloaromatization process were studied by DFT calculations. These ruthenabenzenes display robust catalytic activity for metathesis and other transformations, which illustrates that metallabenzenes are not only compounds of structural and theoretical interests but also are a novel platform for new catalyst development.
Large-Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N-Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context
Czajkowska-Szczykowska, Dorota,Czarnocki, Stefan,Grela, Karol,Kajetanowicz, Anna,Ma?ecki, Pawe?,Niena?towski, Tomasz,Paw?owska, Jolanta,Szczepanik, Pawe?
supporting information, p. 15708 - 15717 (2020/12/01)
A large-scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N-heterocyclic carbene (NHC) ligand with one 2,5-diisopropylphenyl (DIPP) and one thiophenylmethylene N-substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile of the obtained catalyst was studied in environmentally friendly dimethyl carbonate (DMC). Although VII exhibited low efficiency in cross-metathesis (CM) with electron-deficient partners, good to excellent results were noted for substrates featuring easy to isomerise C?C double bonds. This includes polyfunctional substrates of medicinal chemistry interest, such as analogues of psychoactive 5F-PB-22 and NM-2201 and two PDE5 inhibitors—Sildenafil and Vardenafil. Finally, a larger scale ring-closing metathesis (RCM) of a Vardenafil derivative was conducted in DMC, allowing for straightforward isolation of the expected product (23 g) in high yield and with low Ru contamination level (7.7 ppm).
Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions: Auto-assembling Reagents Involving a Fully Recyclable Ligand
Rouen, Mathieu,Chaumont, Pauline,Barozzino-Consiglio, Gabriella,Maddaluno, Jacques,Harrison-Marchand, Anne
supporting information, p. 9238 - 9242 (2018/06/04)
A methodology consisting in carrying out enantioselective nucleophilic 1,2-additions (ee values up to 97 %) from cheap, easily accessible, and never described before, chiral lithium amido zincates is presented. These multicomponent reactants auto-assemble when mixing, in a 1:1 ratio, a homoleptic diorganozinc (R2Zn) with a chiral lithium amide (CLA). The latter, obtained after a single reductive amination, plays the role of the chiral inductor and is fully recoverable thanks to a simple acid–base wash, allowing being recycled and re-use without loss of stereochemical information.
Purple acid phosphatase inhibitors as leads for osteoporosis chemotherapeutics
Hussein, Waleed M.,Feder, Daniel,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
, p. 462 - 479 (2018/08/21)
Purple acid phosphatases (PAPs) are metalloenzymes that catalyse the hydrolysis of phosphate esters under acidic conditions. Their active site contains a Fe(III)Fe(II) metal centre in mammals and a Fe(III)Zn(II) or Fe(III)Mn(II) metal centre in plants. In humans, elevated PAP levels in serum strongly correlate with the progression of osteoporosis and metabolic bone malignancies, which make PAP a target suitable for the development of chemotherapeutics to combat bone ailments. Due to difficulties in obtaining the human enzyme, the corresponding enzymes from red kidney bean and pig have been used previously to develop specific PAP inhibitors. Here, existing lead compounds were further elaborated to create a series of inhibitors with Ki values as low as ～30 μM. The inhibition constants of these compounds were of comparable magnitude for pig and red kidney bean PAPs, indicating that relevant binding interactions are conserved. The crystal structure of red kidney bean PAP in complex with the most potent inhibitor in this series, compound 4f, was solved to 2.40 ? resolution. This inhibitor coordinates directly to the binuclear metal centre in the active site as expected based on its competitive mode of inhibition. Docking simulations predict that this compound binds to human PAP in a similar mode. This study presents the first example of a PAP structure in complex with an inhibitor that is of relevance to the development of anti-osteoporotic chemotherapeutics.
Modulators of protease activated receptors
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Page/Page column 30, (2018/02/20)
The present invention provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for therapies such as metabolic syndrome, obesity, type II diabetes, fibrosis and cardiovascular diseases, whether they are used alone or in combination with other treatment modalities.
Hydride transfer reactions of 5-(2-alkohybenzylidene) barbituric acids: Synthesis of 2,4,6-trioxoperhydropyrimidine-5-spiro-3′-chromanes
Krasnov, Konstantin A.,Dorovatovskii, Pavel V.,Zubavichus, Yan V.,Timofeeva, Tatiana V.,Khrustalev, Victor N.
, p. 542 - 549 (2017/01/12)
The thermal cyclization of 5-(2-phenoxymethylphenyl-methylene)barbituric acid and its derivatives affords 2,4,6-trioxoperhydropyrimidine-5-spiro-3′-chromanes. The reactions require no catalysts and proceed at temperatures from 118 to 240?°C depending on the substrate activity. These cyclization reactions are analogous to T-reactions of tertiary amines involving the hydride transfer.
Chelating carbene ligand precursors and their use in the synthesis of metathesis catalysts
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Page/Page column 10, (2016/12/22)
Chelating ligand precursors for the preparation of olefin methathesis catalysts are disclosed. The resulting catalysts are air stable monomeric species capable of promoting various methathesis reactions efficiently, which can be recovered from the reaction mixture and reused. Internal olefin compounds, specifically beta-substituted styrenes, are used as ligand precursors. Compared to terminal olefin compounds such as unsubstituted styrenes, the beta-substituted styrenes are easier and less costly to prepare, and more stable since they are less prone to spontaneous polymerization. Methods of preparing chelating-carbene methathesis catalysts without the use of CuCl are disclosed. This eliminates the need for CuCl by replacing it with organic acids, mineral acids, mild oxidants or even water, resulting in high yields of Hoveyda-type methathesis catalysts. The invention provides an efficient method for preparing chelating-carbene metathesis catalysts by reacting a suitable ruthenium complex in high concentrations of the ligand precursors followed by crystallization from an organic solvent.
HETEROCYCLIC DERIVATIVES AS RORGAMMA MODULATORS
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Page/Page column 73, (2016/07/27)
The present invention provides novel compounds of formula (I) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, fibrotic diseases, or cholestatic diseases.
