- Novel cobalt-valine catalyzed O-arylation of phenols with electron deficient aryl iodides
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Abstract: A Novel cobalt-catalyzed O-arylation of phenols with electron deficient aryl iodides is described. The reaction employs cheap and easy-to-handle cobalt acetate tetrahydrate as the catalyst precursor and naturally occurring l-valine as the ligand without the use of any transmetallating or reducing agents. The new protocol offers a wide scope for a variety of phenols towards O-arylation with moderate to excellent yields with electron deficient aryl iodides.
- Ujwaldev, Sankuviruthiyil M.,Saranya, Salim,Harry, Nissy Ann,Anilkumar, Gopinathan
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p. 339 - 346
(2019/01/18)
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- Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
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A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding Ki and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both Gq-coupled intracellular Ca2+ flux and Gs-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.
- Jurica, Elizabeth A.,Wu, Ximao,Williams, Kristin N.,Hernandez, Andres S.,Nirschl, David S.,Rampulla, Richard A.,Mathur, Arvind,Zhou, Min,Cao, Gary,Xie, Chunshan,Jacob, Biji,Cai, Hong,Wang, Tao,Murphy, Brian J.,Liu, Heng,Xu, Carrie,Kunselman, Lori K.,Hicks, Michael B.,Sun, Qin,Schnur, Dora M.,Sitkoff, Doree F.,Dierks, Elizabeth A.,Apedo, Atsu,Moore, Douglas B.,Foster, Kimberly A.,Cvijic, Mary Ellen,Panemangalore, Reshma,Flynn, Neil A.,Maxwell, Brad D.,Hong, Yang,Tian, Yuan,Wilkes, Jason J.,Zinker, Bradley A.,Whaley, Jean M.,Barrish, Joel C.,Robl, Jeffrey A.,Ewing, William R.,Ellsworth, Bruce A.
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supporting information
p. 1417 - 1431
(2017/03/08)
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- N-Picolinamides as ligands in Ullman type C–O coupling reactions
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Copper-catalyzed modified Ullmann coupling reactions creating C–O bonds, including diaryl ethers or phenols, are vital to organic synthesis. Synthesized N-phenyl-2-pyridinecarboxamide and its derivatives were used as ligands in conjunction with catalytic copper sources in the formation of various diaryl ethers and phenols. Various aryl and heteroaryl halides with electron donating and withdrawing groups were reacted with various phenols under mild reaction conditions providing moderate to excellent yields.
- Damkaci, Fehmi,Sigindere, Cihad,Sobiech, Thomas,Vik, Erik,Malone, Joshua
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supporting information
p. 3559 - 3564
(2017/10/05)
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- Ullmann Coupling Reaction of Nitro-Substituted Aryl Halides with Phenols under Mild Conditions: Micro-/Mesoporous Hierarchical LaAlPO-5 Zeolite Catalyst
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Heterogeneous catalytic reactions of aromatic organic molecules over zeolite catalysts present many challenges because of the shape selectivity of the micropores of conventional zeolites that limits the diffusion of aromatic molecules. Herein, Ullmann coupling reactions of phenols with nitro-substituted aryl halides were catalyzed by rare-earth-doped mesoporous AlPO-5 zeolites in the absence of ligands. The AlPO-5-MAlPO-5-M zeolites had a pure AFI structure and consisted of spherical particles assembled by nanofibers. The rare-earth elements were highly dispersed in the AlPO-5-MAlPO-5-M samples. The LaAlPO-5-MAlPO-5-M zeolite is an excellent catalyst for Ullmann coupling reactions of phenols and nitro-substituted aryl halides. Mesoporous LaAlPO-5 has an excellent stability and recyclability in the Ullmann coupling of p-X-nitrobenzene (X=Cl, Br, and I) with 2-naphthol. These results are important in the exploration of attractive Ullmann coupling reactions and in the development of mesoporous zeolite catalysts for other organic reactions.
- Ke, Qingping,Wu, Mingzhou,Wang, Chao,Lu, Guanzhong
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p. 1557 - 1563
(2016/05/02)
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- Picolinamides as effective ligands for copper-catalysed aryl ether formation: Structure-activity relationships, substrate scope and mechanistic investigations
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The use of picolinic acid amide derivatives as an effective family of bidentate ligands for copper-catalysed aryl ether synthesis is reported. A fluorine-substituted ligand gave good results in the synthesis of a wide range of aryl ethers. Even bulky phenols, known to be very challenging substrates, were shown to react with aryl iodides with excellent yields using these ligands. At the end of the reaction, the first examples of end-of-life Cu species were isolated and identified as CuII complexes with several of the anionic ligands tested. A preliminary mechanistic investigation is reported that suggests that the substituents on the ligands might have a crucial role in determining the redox properties of the metal centre and, consequently, its efficacy in the coupling process. An understanding of these effects is important for the development of new efficient and tunable ligands for copper-based chemistry.
- Sambiagio, Carlo,Munday, Rachel H.,Marsden, Stephen P.,Blacker, A. John,McGowan, Patrick C.
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supporting information
p. 17606 - 17615
(2015/02/05)
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- First palladium-catalyzed denitrated coupling reaction of nitroarenes with phenols
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The first palladium-catalyzed protocol for the denitrated coupling reaction of nitroarenes with phenols has been developed, achieving unsymmetrical diaryl ethers in moderate to excellent yields. The cyclopalladated ferrocenylimine (catalyst Ic) exhibited highly catalytic activity for this transformation with low catalyst loading (0.75 mol%) and short reaction time (2 h). The efficiency of this reaction was demonstrated by its compatibility with a range of groups. Moreover, the rigorous exclusion of air or moisture was not required in these transformations. Copyright
- Wang, Hailei,Yu, Ajuan,Cao, Aijuan,Chang, Junbiao,Wu, Yangjie
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p. 611 - 614
(2013/10/21)
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- Palladium nanoparticles supported on silica diphenylphosphinite as efficient catalyst for C-O and C-S arylation of aryl halides
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Silica diphenylphosphinite (SDPP) can be easily obtained through direct phosphorylation of silica gel. Further reaction of SDPP with Pd(II) produces nano Pd(0)/SDPP. This nano Pd(0) catalyst exhibits excellent reactivity for the C-O and C-S arylation of different aryl iodides, bromides and chloride with phenols and thiophenols. This heterogeneous catalyst shows excellent recyclability and can be easily recovered and reused for several runs. Copyright
- Iranpoor, Nasser,Firouzabadi, Habib,Rostami, Abed
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p. 501 - 506
(2013/09/23)
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- PROCESS FOR THE CATALYTIC SYNTHESIS OF DIARYL ETHERS
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Described is a process for preparing diaryl ethers of the formula (I) [in-line-formulae]Ar—O—Ar′??(I)[/in-line-formulae]In which Ar is an aryl or substituted aryl group and Ar′ is an aryl, substituted aryl, heteroaryl or substituted heteroaryl group,by reacting an aryl of formula (II) or a aryloxy salt of formula (III) [in-line-formulae]Ar—OH ??(II)[/in-line-formulae] [in-line-formulae]Ar—OR ??(III)[/in-line-formulae]In which Ar has the same meaning as in formula (I) and R is an alkali metal,with an aryl or heteroaryl bromide of formula (IV) [in-line-formulae]Ar′—Br ??(IV)[/in-line-formulae]In which Ar′ has the same meaning as in formula (I),characterized in that the reaction is carried out in the presence of a copper(I)salt and a 1-substituted imidazole as catalyst system.
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Page/Page column 3; 5
(2009/06/27)
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- Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase
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Leukotriene B4 (LTB4) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB4 and possibly identify novel treatments, inhibitors of the LTB4 biosynthetic enzyme, leukotriene A4 hydrolase (LTA4-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA4-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.
- Kirkland, Thomas A.,Adler, Marc,Bauman, John G.,Chen, Ming,Haeggstroem, Jesper Z.,King, Beverly,Kochanny, Monica J.,Liang, Amy M.,Mendoza, Lisa,Phillips, Gary B.,Thunnissen, Marjolein,Trinh, Lan,Whitlow, Marc,Ye, Bin,Ye, Hong,Parkinson, John,Guilford, William J.
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p. 4963 - 4983
(2008/12/21)
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- Copper-catalyzed Ullmann coupling under ligand- and additive- free conditions. Part 1: O-Arylation of phenols with aryl halides
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O-Arylation of a wide variety of substituted phenols and aliphatic alcohols with aryl halides catalyzed by copper iodide under mild ligand and additive free conditions (nBu4NBr, DMF, K3PO4, reflux, 22 h) is accomplished in good to excellent product yields (up to 95%).
- Chang, Joyce Wei Wei,Chee, Sheena,Mak, Shiya,Buranaprasertsuk, Pongchart,Chavasiri, Warinthorn,Chan, Philip Wai Hong
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p. 2018 - 2022
(2008/09/19)
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- Bio-inspired copper catalysts for the formation of diaryl ethers
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Aryl bromides and phenols are coupled efficiently to the corresponding diaryl ethers in the presence of a practical Cu(I)/1-butylimidazole catalyst system. The convenient protocol is applied successfully to the synthesis of 16 different diaryl ethers in high yield and selectivity.
- Schareina, Thomas,Zapf, Alexander,Cotté, Alain,Müller, Nikolaus,Beller, Matthias
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p. 1851 - 1855
(2008/09/18)
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- Microwave assisted aromatic nucleophilic substitution reaction under solventless condition
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We report here microwave assisted aromatic nucleophilic substitution reaction of 1-chloro-4-nitrobenzene with different phenoxides.
- Rebeiro, Geeta L.,Khadilkar, Bhushan M.
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p. 1405 - 1410
(2007/10/03)
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- Synthesis of diaryl ethers using an easy-to-prepare, air-stable, soluble copper(I) catalyst
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We have found that bromo(triphenylphosphine)copper(I), an air-stable and soluble copper(I) complex, can be used as a catalyst in the synthesis of diaryl ethers. Using this catalyst, we have synthesized diaryl ethers from electron-rich aryl bromides and electron-rich phenols in the presence of cesium carbonate, in 17-24 h, in NMP. We also found that electron-deficient aryl bromides couple with phenols in the presence of cesium carbonate, in 6 h in NMP at 70°C, without the catalyst.
- Gujadhur,Venkataraman
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p. 2865 - 2879
(2007/10/03)
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- CsF-Al2O3 mediated rapid condensation of phenols with aryl halides: Comparative study of conventional heating vs. microwave irradiation
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Biaryl ethers and thio ethers are formed in high yields by the condensation of phenols and thiophenols with electron-deficient aryl halides using CsF supported on Al2O3 under microwave irradiation in solvent-free conditions.
- Yadav, Jhillu S.,Subba Reddy, Basi V.
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p. 489 - 491
(2007/10/03)
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- Design and synthesis of aryloxyethyl thiocyanate derivatives as potent inhibitors of Trypanosoma cruzi proliferation
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As a part of our project directed at the search of new chemotherapeutic agents against American trypanosomiasis (Chagas' disease), several drugs possessing the 4-phenoxyphenoxy skeleton and other closely related structures employing the thiocyanate moiety as polar end group were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for this disease. These thiocyanate analogues were envisioned bearing in mind the potent activity shown by 4- phenoxyphenoxyethyl thiocyanate (compound 8) taken as lead drug. This compound had previously proved to be an extremely active growth inhibitor against T. cruzi with IC50 values ranging from the very low micromolar level in epimastigotes to the low nanomolar level in the intracellular form of the parasite. Of the designed compounds, the ethyl thiocyanate drugs connected to nonpolar skeletons, namely, arylthio, 2,4-dichlorophenoxy, ortho-substituted aryloxy, and 2-methyl-4-phenoxyphenoxy (compounds 15, 34, 47, 52, 72, respectively), were shown to be very potent antireplicative agents against T. cruzi. On the other hand, conformationally restricted analogues as well as branched derivatives at the aliphatic side chain were shown to be moderately active against T. cruzi growth. The biological activity of drugs bearing the thiocyanate group correlated quite well with the activity exhibited by their normal precursors, the tetrahydropyranyl ether derivatives, when bonded to the same nonpolar skeleton. Compounds having the tetrahydropyranyl moiety as polar end were proportionally much less active than sulfur-containing derivatives in all cases. Drugs 47 and 72 also resulted to be very active against the amastigote form of the parasite growing in myoblasts; however, they were slightly less active than the lead drug 8. On the other hand, compounds 34 and 52 were almost devoid of activity against myoblasts. Surprisingly, the dithio derivative 15 was toxic for myoblasts.
- Szajnman, Sergio H.,Yan, Wen,Bailey, Brian N.,Docampo, Roberto,Elhalem, Eleonora,Rodriguez, Juan B.
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p. 1826 - 1840
(2007/10/03)
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- Synthesis of diaryl ethers, diaryl thioethers, and diarylamines mediated by potassium fluoride-alumina and 18-crown-6: Expansion of scope and utility
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An efficient alternative to the Ullmann ether synthesis of diaryl ethers, diaryl thioethers, and diarylamines involving the S(N)Ar addition of a phenol, thiophenol, or aniline to an appropriate aryl halide, mediated by potassium-fluoride alumina and 18-crown-6 in acetonitrile or DMSO, is described. Expansion of the reaction conditions to include DMSO as solvent has resulted in a far greater range of substitution patterns permitted on the electrophile. For example, it was found that electronically unfavorable 3- chlorobenzonitrile could be condensed with 3-methoxyphenol to form the corresponding diaryl ether in 66% yield, a combination not normally amenable to Ullmann coupling. Electron-withdrawing groups present on the electrophile may be as diverse as nitro, cyano, formyl, acetyl, ester, amide, and even aryl. The method features a simple reaction procedure that provides products in generally good to excellent purified yields.
- Sawyer, J. Scott,Schmittling, Elisabeth A.,Palkowitz, Jayne A.,Smith III, William J.
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p. 6338 - 6343
(2007/10/03)
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