- Metathesis and Decomposition of Fischer Carbenes of Cyclometalated Z-Selective Ruthenium Metathesis Catalysts
-
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.
- Ahmed, Tonia S.,Grandner, Jessica M.,Taylor, Buck L. H.,Herbert, Myles B.,Houk,Grubbs, Robert H.
-
-
Read Online
- Synthesis and Reactivity of Homogeneous and Heterogeneous Ruthenium-Based Metathesis Catalysts Containing Electron-Withdrawing Ligands
-
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.
- Krause, Jens O.,Nuyken, Oskar,Wurst, Klaus,Buchmeiser, Michael R.
-
-
Read Online
- Ruthenabenzene: A Robust Precatalyst
-
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.
- Gupta, Saswata,Su, Siyuan,Zhang, Yu,Liu, Peng,Wink, Donald J.,Lee, Daesung
-
supporting information
p. 7490 - 7500
(2021/05/26)
-
- 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
-
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).
- 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)
-
- Chiral Lithium Amido Zincates for Enantioselective 1,2-Additions: Auto-assembling Reagents Involving a Fully Recyclable Ligand
-
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.
- Rouen, Mathieu,Chaumont, Pauline,Barozzino-Consiglio, Gabriella,Maddaluno, Jacques,Harrison-Marchand, Anne
-
supporting information
p. 9238 - 9242
(2018/06/04)
-
- Purple acid phosphatase inhibitors as leads for osteoporosis chemotherapeutics
-
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.
- Hussein, Waleed M.,Feder, Daniel,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
-
p. 462 - 479
(2018/08/21)
-
- Modulators of protease activated receptors
-
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.
- -
-
Page/Page column 30
(2018/02/20)
-
- Hydride transfer reactions of 5-(2-alkohybenzylidene) barbituric acids: Synthesis of 2,4,6-trioxoperhydropyrimidine-5-spiro-3′-chromanes
-
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.
- Krasnov, Konstantin A.,Dorovatovskii, Pavel V.,Zubavichus, Yan V.,Timofeeva, Tatiana V.,Khrustalev, Victor N.
-
p. 542 - 549
(2017/01/12)
-
- Chelating carbene ligand precursors and their use in the synthesis of metathesis catalysts
-
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.
- -
-
Page/Page column 10
(2016/12/22)
-
- HETEROCYCLIC DERIVATIVES AS RORGAMMA MODULATORS
-
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.
- -
-
Page/Page column 73
(2016/07/27)
-
- Remarkable Ability of the Benzylidene Ligand To Control Initiation of Hoveyda–Grubbs Metathesis Catalysts
-
The structure of the chelating benzylidene ligand offers the unique ability to control the initiation of Hoveyda–Grubbs metathesis catalysts. Apart from steric and electronic effects acting on the step involving opening of the chelate ring, changes related to the following ligand-exchange process may also play a critical role. Our mechanistic model reveals that ligands substituted at the 6-position of the benzylidene ring enter the metathesis cycle in a nonoptimal chelating conformation, and thus the coordination number of the ruthenium center transiently increases to six (associative mechanism). In effect, the synthesis and initiation of the catalysts becomes difficult, and the energy barrier of the ligand-exchange process is controlled by the structure of the coordinating OR group. Moreover, we explain how isomeric naphthalene ligands affect the catalytic performance by an indivisible combination of steric and π-electron delocalization effects.
- Basak, Tymoteusz,Grudzień, Krzysztof,Barbasiewicz, Micha?
-
supporting information
p. 3513 - 3523
(2016/07/29)
-
- Pro-angiogenic effects of chalcone derivatives in zebrafish embryos in vivo
-
The aim of this study was to investigate novel chalcones with potent angiogenic activities in vivo. Chalcone-based derivatives were evaluated using a transgenic zebrafish line with fluorescent vessels to real-time monitor the effect on angiogenesis. Results showed that the chalcone analogues did not possess anti-angiogenic effect on zebrafish vasculatures; instead, some of them displayed potent pro-angiogenic effects on the formation of the sub-intestinal vein. Similar pro-angiogenic effects can also be seen on wild type zebrafish embryos. Moreover, the expression of vegfa, the major regulator for angiogenesis, was also upregulated in their treatment. Taken together, we have synthesized and identified a series of novel chalcone-based derivatives as potent in vivo pro-angiogenic compounds. These novel compounds hold potential for therapeutic angiogenesis.
- Chen, Yau-Hung,Chang, Chao-Yuan,Chang, Chiung-Fang,Chen, Po-Chih,Lee, Ya-Ting,Chern, Ching-Yuh,Tsai, Jen-Ning
-
p. 12512 - 12524
(2015/08/06)
-
- Dehydrogenation of perfluoroalkyl ketones by using a recyclable oxoammonium salt
-
A novel dehydrogenation reaction of perfluoroalkyl ketones by the oxoammonium salt 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (4-NHAc-TEMPO+BF4-, Bobbitt's salt, 1) is described. The reaction proceeds under mildly basic conditions and appears to be unique to perfluoroalkyl ketones. A proposed mechanism for this unusual transformation is given. The byproduct of the reaction, 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinyloxy (1a), can easily be recovered and used to regenerate the oxoammonium salt. The dehydrogenation of perfluoroalkyl ketones by using an oxoammonium salt is reported. The reaction proceeds under mildly basic conditions and affords α,β-unsaturated products in fair to excellent yields. The reaction likely proceeds through a two-step sequence. The spent oxidant can easily be recovered and used to regenerate the oxoammonium salt. Copyright
- Hamlin, Trevor A.,Kelly, Christopher B.,Leadbeater, Nicholas E.
-
supporting information
p. 3658 - 3661
(2013/07/19)
-
- ACC INHIBITORS AND USES THEREOF
-
The present invention provides compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
- -
-
Paragraph 1185; 1186; 1187
(2013/05/22)
-
- Nitration under continuous flow conditions: Convenient synthesis of 2-isopropoxy-5-nitrobenzaldehyde, an important building block in the preparation of nitro-substituted Hoveyda-Grubbs metathesis catalyst
-
Herein, we describe the use of continuous flow chemistry for selective, efficient and reproducible nitration of 2-isopropoxybenzaldehyde to produce the desired 2-isopropoxy-5-nitrobenzaldehyde, an important building block in the preparation of a ligand of nitro-substituted Hoveyda-Grubbs metathesis catalyst. Nitration was done with red fuming HNO3, and this challenging and hazardous process was performed using a flow-through silicon-glass microreactor equipped with a set of temperature sensors, and with a productivity of 13 g/h, providing us with a reproducible chemical process amenable for production of sufficient quantities of 2-isopropoxy-5-nitrobenzaldehyde for ongoing large-scale synthesis of nitro-substituted Hoveyda-Grubbs metathesis catalyst.
- Knapkiewicz, Pawel,Skowerski, Krzysztof,Jaskolska, Dagmara E.,Barbasiewicz, Michal,Olszewski, Tomasz K.
-
p. 1430 - 1435
(2012/11/07)
-
- A robust and recyclable ruthenium catalyst immobilised on polyethylene glycol
-
A highly robust and recyclable Hoveyda-Grubbs' second generation ruthenium type catalyst immobilised on polyethylene glycol is conveniently prepared from Grubbs' second generation catalyst. The catalyst performs ring-closing metathesis of various di-and tri-substituted olefins efficiently in dichloromethane in air.
- Zaman, Shazia,Abell, Andrew D.
-
scheme or table
p. 5340 - 5343
(2010/01/18)
-
- NOVEL PHENYL-ISOXAZOL-3-OL DERIVATIVE
-
The present invention relates to a compound represented by formula (I), which has a GPR120 agonist action and thus is useful for treatment of diabetes mellitus or hyperlipidemia, or a pharmaceutically acceptable salt thereof. In the formula, (AA) represents a phenyl or the like, which may be substituted with a lower alkoxy group or the like; (BB) represents a divalent group or the like, derived by removal of two hydrogen atoms from a benzene which may be substituted with a halogen atom or the like; X represents a spacer having a main chain composed of 1-8 carbon atoms wherein 1-3 carbon atoms in the main chain may be substituted with an oxygen atom or the like; and Y represents a hydrogen atom or the like.
- -
-
Page/Page column 34
(2009/09/26)
-
- C-H bond functionalization via hydride transfer: synthesis of dihydrobenzopyrans from ortho-vinylaryl akyl ethers
-
The hydride transfer initiated cyclization ("HT-cyclization") of aryl alkyl ethers, which leads to direct coupling of sp3 C-H bonds and activated alkenes, is reported. Readily available salicylaldehyde derived ethers are converted in one step to dihydrobenzopyrans, an important class of heteroarenes frequently found in biologically active compounds. This process has not been previously reported, in contrast to known HTcyclizations of the corresponding fert-amines ("tert-amino effect" reactions).
- McQuaid, Kevin M.,Long, Jonathan Z.,Sames, Dalibor
-
supporting information; experimental part
p. 2972 - 2975
(2009/12/05)
-
- Competitive formation of β-amino acids, propenoic, and ylidenemalonic acids by the Rodionov reaction from malonic acid, aldehydes, and ammonium acetate in alcoholic medium
-
The Rodionov reaction of 49 available aliphatic and aromatic aldehydes with malonic acid and ammonium acetate in alcoholic medium, resulting in formation of β-amino acids, propenoic, and ylidenemalonic acids, was studied. Certain regioselectivity regularities of the reaction were revealed. Among the variety of ketones studied, cyclohexanone is the only whose reaction yields a β-amino acid. Unusual dehydrofluorination of 6-chloro-2-fluorocinnamic acid under the Rodionov reaction was discovered. 2005 Pleiades Publishing, Inc.
- Lebedev,Lebedeva,Sheludyakov,Kovaleva,Ustinova,Kozhevnikov
-
p. 1113 - 1124
(2007/10/03)
-
- Compositions containing aromatic aldehydes and their use in treatments
-
Disclosed are pharmaceutical and cosmetic compositions containing aromatic aldehyde compounds. Some of the disclosed compositions are useful as topical therapeutics for treating inflammatory dermatologic conditions. Some of the compositions are useful in transdermal and other systemic dose forms for treating other inflammatory conditions in mammals.
- -
-
-
- Reactions of 1-(2-alkoxyphenyl)alkaniminyl radicals
-
Reactions of 1-(2-alkoxyphenyl)alkaniminyl radicals were studied. Generation of the iminyls 1d and 1e by standard methods in the gas-phase by flash vacuum pyrolysis (FVP) gives rise to 1,3-benzoxazines 18 and 22 by a mechanism which probably involves a 1,6-hydrogen atom translocation. The results showed that the dealkylation is an integral part of the reaction mechanism and not a subsequent reaction of 2-alkoxybenzonitriles.
- Leardini, Rino,McNab, Hamish,Minozzi, Matteo,Nanni, Daniele,Reed, David,Wright, Andrew G.
-
p. 2704 - 2710
(2007/10/03)
-
- Ukokinase inhibitors
-
Compounds having the formula are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions and a method of inhibiting urokinase in a mammal.
- -
-
-
- A recyclable Ru-based metathesis catalyst
-
A Ru carbene (8, Scheme 2) that contains an internal metal-oxygen chelate is an active metathesis catalyst and is readily obtained by the sequential treatment of Cl2Ru(PPh3)3 with (2-isopropoxyphenyl)- diazomethane and PCy3. This Ru-carbene complex offers excellent stability to air and moisture and can be recycled in high yield by silica gel column chromatography. The structures of this and related complexes have been unambiguously established by NMR and single-crystal X-ray diffraction studies.
- Kingsbury, Jason S.,Harrity, Joseph P. A.,Bonitatebus Jr., Peter J.,Hoveyda, Amir H.
-
p. 791 - 799
(2007/10/03)
-
- Cesium fluoride-mediated claisen rearrangements of phenyl propargyl ethers: Substituent effects of an orthoalkoxy group on the benzene ring or modified propargyl residues
-
The expected 7-alkoxy-2-methylbenzo[b]furans were effectively given in the CsF-mediated Claisen rearrangement of phenyl propargyl ethers with an o-alkoxy substituent on the benzene ring. On the other hand CsF did not affect the production of the corresponding benzo[b]furans when ethers, carrying a propargyl residue modified by either 1,1-dimethyl or 3-ethoxycarbonyl functions, were used as substrates in the rearrangement.
- Ishikawa, Tsutomu,Mizutani, Akiko,Miwa, Chizue,Oku, Yumie,Komano, Naoko,Takami, Atsuya,Watanabe, Toshiko
-
p. 2261 - 2272
(2007/10/03)
-
- Productivity in synthesis: A mixture protocol to raise compound output is demonstrated for asymmetric cyclopropanation of allyl alcohols
-
The productivity of conventional chemical reactions can be improved in favourable cases by using a mixture protocol. This concept is demonstrated for the asymmetric cyclopropanation of 3-arylprop-2-en-1-ols. Mixtures of three or four starting materials give products which are separated by flash chromatography. The enantiomeric excess and yield of each pure compound is comparable to that obtained in conventional single-substrate reactions, leading to an overall efficiency gain, especially in experimentalist effort, and reduced hazard.
- Turnbull, Michael D.
-
p. 1241 - 1247
(2007/10/03)
-
- Photocyclization Reactions. Part 1. Synthesis of Dihydrobenzofuranols Using Photocyclization of 2-Alkoxybenzaldehydes, 2'-Alkoxyacetophenones, 2-Formylphenoxyacetic Acids and 2-Acetylphenoxyacetic Acids
-
Photocyclization reactions were carried out on 2-alkoxybenzaldehydes 1a-f, 2'-alkoxyacetophenones 2a-h, 2-formylphenoxyacetic acids 1i-l and 2-acetylphenoxyacetic acids 2i-m.Irradiation opf 1a-f and 2a-h in acetonitrile gave the corresponding dihydrobenzofuranols 3, 5 and dihydroisobenzofuranols 4, 6.Using carboxylic acids 1i-l, 2i-m as starting materials, decarboxylation occurred immediately to give the corresponding ethers 1a-d, 2a-e.Further irradiation of the solution afforded dihydrobenzofuranols 3,5 and dihydroisobenzofuranols 4, 6.Substituent effects on photocyclization and reaction pathways are discussed.
- Horaguchi, Takaaki,Tsukada, Chikara,Hasegawa, Eietsu,Shimizu, Takahachi,Suzuki, Tsuneo,Tanemura, Kiyoshi
-
p. 1261 - 1272
(2007/10/02)
-