- Pd/Cu-Catalyzed C-H/C-H Cross Coupling of (Hetero)Arenes with Azoles through Arylsulfonium Intermediates
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A highly efficient method for the selective formal C-H/C-H cross-coupling of azoles and (hetero)arenes was established through arylsulfonium intermediates under transition-metal catalysis, which produced a variety of 2-(hetero)aryl azoles in good to excellent yields. Advantages of the reaction included mildness, a good functional group tolerance, a wide range of substrates, a high regio- and chemoselectivity, one-pot procedures, and the late-stage functionalization of complex molecules without the use of oxidants, offering a promising strategy for the transition-metal-catalyzed C-H arylation of azoles.
- Lin, Zeng-Hui,Tian, Ze-Yu,Zhang, Cheng-Pan
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supporting information
p. 4400 - 4405
(2021/06/27)
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- Visible Light-Induced Copper-Catalyzed C—H Arylation of Benzoxazoles?
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A general method for visible light-induced copper-catalyzed arylation of sp2 C—H bonds of azoles has been developed. The method employs aryl halide as the coupling partner, lithium alkoxide as base. A variety of azoles including benzooxazole and benzothiazole can be arylated. Furthermore, electron-poor heterocycles such as thiophene possessing one electron-withdrawing group can also be arylated.
- Ma, Xiaodong,Zhang, Guozhu
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supporting information
p. 1299 - 1303
(2020/08/05)
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- Copper-Catalyzed Intramolecular C-H Amination: A New Entry to Substituted Xanthine Derivatives
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Catalytic synthesis of xanthines was achieved in the presence of a copper catalyst. The process involves copper-catalyzed intramolecular C-H amination of benzamidines that possess a uracil moiety and produces variously substituted xanthines generally in good to high yields. This work introduces a new, facile approach to polysubstituted xanthine compounds..
- Shimizu, Maki,Hayama, Noboru,Kimachi, Tetsutaro,Inamoto, Kiyofumi
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p. 4183 - 4190
(2017/09/12)
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- Unprecedented salt-promoted direct arylation of acidic sp2 C[sbnd]H bonds under heterogeneous Ni-MOF-74 catalysis: Synthesis of bioactive azole derivatives
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Herein, nickel-based metal-organic framework, Ni-MOF-74, was synthesized by a solvothermal method and its properties was characterized by a host of techniques. Ni-MOF-74 exhibited exceptional catalytic activity toward the direct arylation of azoles via C[sbnd]H activation while other Ni-MOFs, nickel-based heterogeneous systems, and homogeneous counter parts displayed lower activity. Optimal conditions involved the use of Li2CO3 or KCl salts in diglyme solvent in 18 h and no additional ligand is required. This is the first and unprecedented report using KCl salt as promoter for arylation of heterocycles. By avoiding the use of strong bases and oxidants, optimized conditions are compatible with wide range of functional groups and heterocycles. Furthermore, by taking advantage of large aperture size of Ni-MOF-74, we are able to utilize optimized conditions to successfully synthesize several bioactive arylated azole derivatives. Previous studies using heterogeneous catalysts to approach these bioactive compounds are not performed in the literature. Leaching tests indicated that homogeneous catalysis via leached active nickel species is unlikely. Thus, the catalyst was facilely separated from the reaction mixture and reused several times without significant degradation of the catalytic reactivity.
- Nguyen, Huong T.T.,Doan, Duc N.A.,Truong, Thanh
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p. 141 - 149
(2016/12/09)
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- Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts
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Arylation, vinylation, and alkynylation of electron-deficient arenes and heteroarenes have been achieved by chemoselective C-H zincation followed by copper-catalyzed coupling reactions using iodonium salts. This approach offers a direct and general access to a wide scope of (hetero)biaryls as well as alkenylated and alkynylated heteroarenes under mild conditions. It is particularly useful and valuable for the rapid and modular synthesis of diverse (hetero)aryl compounds, as demonstrated in the synthesis of transient receptor potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1 receptor) antagonists.
- Liu, Chuan,Wang, Qiu
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supporting information
p. 5118 - 5121
(2016/10/14)
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- Iron catalyzed oxidative assembly of N-heteroaryl and aryl metal reagents using oxygen as an oxidant
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An equivalent amount of N-heteroaryl and aryl Grignard or lithium reagents, after mediation by an equivalent of titanate, was facilely coupled to furnish N-heteroaryl-aryl compounds under the catalysis of FeCl3/TMEDA at ambient temperature using oxygen as an oxidant. Most of the common N-heteroaryls were all good candidates, and thus provided a general, green and pratical protocol for the flexible construction of various N-heteroaryl-aryl structures. This journal is
- Liu, Kun Ming,Liao, Lian Yan,Duan, Xin Fang
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supporting information
p. 1124 - 1127
(2015/01/09)
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- Direct arylation of n-heteroarenes with aryldiazonium salts by photoredox catalysis in water
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A highly effective visible light-promoted "radical-type" coupling of N-heteroarenes with aryldiazonium salts in water has been developed. The reaction proceeds at room temperature with [Ru(bpy)3]Cl 2×6 H2O as a photosensit
- Xue, Dong,Jia, Zhi-Hui,Zhao, Cong-Jun,Zhang, Yan-Yan,Wang, Chao,Xiao, Jianliang
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supporting information
p. 2960 - 2965
(2014/03/21)
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- Synthesis and characterization of amino-NHC coinage metal complexes and application for C-H activation of caffeine
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This paper describes the synthesis and characterization of silver, copper and gold complexes supported by several amino-NHC ligands with different amino side arms. The transmetallation process using silver-NHC complexes can be used to prepare amino-NHC copper and gold complexes easily in high yield. In addition, the catalytic activities of copper complexes are examined for arylation of caffeine via C-H bond activation.
- Huang, Hsuan-Jui,Lee, Wei-Chih,Yap, Glenn P.A.,Ong, Tiow-Gan
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- Cobalt induced C-H bond activation and C8-arylation of caffeine with aryl bromides
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The 8-caffeinyl cobalt(I) complex (C8-caffeinyl)Co(PMe3) 4 (1) was obtained by reaction of caffeine with cobalt(I) complex CoMe(PMe3)4 via CH bond activation with the escape of methane. The reaction of 1 with ar
- Zheng, Tingting,Sun, Hongjian,Lu, Faguan,Harms, Klaus,Li, Xiaoyan
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p. 139 - 142
(2013/07/25)
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- Copper-catalyzed direct thiolation of xanthines and related heterocycles with disulfides
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A novel copper-catalyzed, base-free direct thiolation of xanthines and related heterocycles is described, featuring the use of inexpensive Cu(OAc) 2·H2O as the catalyst, O2 as a clean and cheap oxidant, and easy-to-handle
- He, Zuying,Luo, Fang,Li, Yinglong,Zhu, Gangguo
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p. 5907 - 5910
(2013/10/21)
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- Palladium-catalyzed direct arylation of N-heteroarenes with arylsulfonyl hydrazides
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Hydrazides applied: A palladium-catalyzed direct Ci-H arylation of heteroarenes, with arylsulfonyl hydrazides as the arylating reagents, has been developed (see scheme). The reaction is chemoselective, in that arylsulfonyl hydrazides containing halogen substituents can be employed without participation of the halogen substituent in the reaction. The method offers a straightforward approach to a variety of aryl-heteroaryl compounds. Copyright
- Liu, Bo,Li, Jian,Song, Feijie,You, Jingsong
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supporting information; experimental part
p. 10830 - 10833
(2012/09/22)
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- Double C-H activation: The palladium-catalyzed direct C-arylation of xanthines with arenes
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The novel Pd-catalyzed C(sp2)-H/C(sp2)-H cross-coupling of unactivated xanthines with unactivated arenes utilizing a combination of Ag(I) and O2 as oxidants exclusively yields C-8 arylated xanthines in a single synthetic o
- Malakar, Chandi C.,Schmidt, Dietmar,Conrad, Juergen,Beifuss, Uwe
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scheme or table
p. 1378 - 1381
(2011/05/03)
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- Palladium-catalyzed desulfitative C-H arylation of heteroarenes with sodium sulfinates
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Desulfitative C-H arylation: Palladium-catalyzed desulfitative C-H arylation of heteroarenes with sodium sulfinates has been disclosed to construct aryl-heteroaryl bonds without the need for any extra ligands (see scheme). Copyright
- Liu, Bo,Guo, Qiang,Cheng, Yangyang,Lan, Jingbo,You, Jingsong
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supporting information; experimental part
p. 13415 - 13419
(2012/01/03)
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- A palladium/copper bimetallic catalytic system: Dramatic improvement for Suzuki-Miyaura-type direct C-H arylation of azoles with arylboronic acids
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Bimetallic catalytic system: Palladium/copper bimetallic-catalyzed Suzuki-Miyaura-type coupling has been disclosed for direct C-H arylation of azoles, instead of azole halides or pseudohalides, with arylboronic acids (see scheme).
- Liu, Bo,Qin, Xurong,Li, Kaizhi,Li, Xiyu,Guo, Qiang,Lan, Jingbo,You, Jingsong
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supporting information; experimental part
p. 11836 - 11839
(2011/01/12)
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- Palladium-catalyzed direct arylations of heteroarenes with tosylates and mesylates
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(Chemical Equation Presented) A toss up: A highly active palladium complex enabled the first direct arylation of heteroarenes through C-H bond functionalization using tosylates or mesylates as electrophiles with ample scope.
- Ackermann, Lutz,Althammer, Andreas,Fenner, Sabine
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supporting information; experimental part
p. 201 - 204
(2009/04/10)
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- Phosphine-free, palladium-catalyzed arylation of heterocycles through C-H bond activation with pivalic acid as a cocatalyst
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A new palladium-catalyzed methodology was developed for the direct C-arylation of azoles with a broad spectrum of aryl bromides without the presence of phosphines, the aid of CuI, or other metal additives by using pivalic acid as a cocatalyst. The method also allowed the direct C-arylation of the N-heterocycle N-oxides, and to a lesser degree, the perfluoroaromatics. It was also found that the method can not only be applied to the synthesis of 8-aryl-substituted caffeines, but also 8-arylated theophyllines and theobromines. The result showed thatthe method can tolerate an array of functional groups including ester, nitrile, nitro, aldehyde, methoxy, trifluoromethyl, fluoro, and chloro substituents, and can found its applications in a number of fields such as synthetic and medicinal chemistry both in industry and in academia.
- Zhao, Dongbing,Wang, Weida,Lian, Shuang,Yang, Fei,Lan, Jingbo,You, Jingsong
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supporting information; experimental part
p. 1337 - 1340
(2009/09/04)
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- Dual inhibition of monoamine oxidase B and antagonism of the adenosine A2A receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues
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The adenosine A2A receptor has emerged as an attractive target for the treatment of Parkinson's disease (PD). Evidence suggests that antagonists of the A2A receptor (A2A antagonists) may be neuroprotective and may help to alleviate the symptoms of PD. We have reported recently that several members of the (E)-8-styrylcaffeine class of A2A antagonists also are potent inhibitors of monoamine oxidase B (MAO-B). Since MAO-B inhibitors are known to possess anti-parkinsonian properties, dual-target-directed drugs that block both MAO-B and A2A receptors may have enhanced value in the management of PD. In an attempt to explore this concept further we have prepared three additional classes of C-8 substituted caffeinyl analogues. The 8-phenyl- and 8-benzylcaffeinyl analogues exhibited relatively weak MAO-B inhibition potencies while selected (E,E)-8-(4-phenylbutadien-1-yl)caffeinyl analogues were found to be exceptionally potent reversible MAO-B inhibitors with enzyme-inhibitor dissociation constants (Ki values) ranging from 17 to 149 nM. Furthermore, these (E,E)-8-(4-phenylbutadien-1-yl)caffeines acted as potent A2A antagonists with Ki values ranging from 59 to 153 nM. We conclude that the (E,E)-8-(4-phenylbutadien-1-yl)caffeines are a promising candidate class of dual-acting compounds.
- Pretorius, Judey,Malan, Sarel F.,Castagnoli Jr., Neal,Bergh, Jacobus J.,Petzer, Jacobus P.
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p. 8676 - 8684
(2008/12/23)
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- A general method for copper-catalyzed arylation of arene C-H bonds
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A general method for copper-catalyzed arylation of sp2 C-H bonds with pKa's below 35 has been developed. The method employs aryl halide as the coupling partner, lithium alkoxide or K3PO4 base, and DMF, DMPU, or mixed DMF/xylenes solvent. A variety of electron-rich and electron-poor heterocycles such as azoles, caffeine, thiophenes, benzofuran, pyridine oxides, pyridazine, and pyrimidine can be arylated. Furthermore, electron-poor arenes possessing at least two electron-withdrawing groups on a benzene ring can also be arylated. Two arylcopper-phenanthroline complex intermediates were independently synthesized.
- Do, Hien-Quang,Khan, Rana M. Kashif,Daugulis, Olafs
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supporting information; experimental part
p. 15185 - 15192
(2009/03/12)
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- Palladium bis(2,2,6,6-tetramethyl-3,5-heptanedionate): an efficient catalyst for regioselective C-2 arylation of heterocycles
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Palladium bis(2,2,6,6-tetramethyl-3,5-heptanedionate), a structurally well defined O-containing transition metal complex is reported as an efficient catalyst for regioselective direct C-2 arylation of heterocycles with aryl halides. The present protocol is applicable to a wide variety of heterocycles providing good to excellent yields of products.
- Nandurkar, Nitin S.,Bhanushali, Mayur J.,Bhor, Malhari D.,Bhanage, Bhalchandra M.
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p. 1045 - 1048
(2008/09/17)
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- Copper-catalyzed arylation of heterocycle C-H bonds
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A new method for the direct, copper-catalyzed arylation of heterocycle C-H bonds by aryl halides has been developed. In addition to electron-rich five-membered heterocycles, electron-poor pyridine oxides can also be arylated. The best results are obtained by using a combination of lithium tert-butoxide base, aryl iodide coupling partner, and copper iodide catalyst. Copyright
- Do, Hien-Quang,Daugulis, Olafs
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p. 12404 - 12405
(2008/09/17)
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- Synthesis of 8-substituted xanthine derivatives by Suzuki cross-coupling reaction
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A Suzuki cross-coupling reaction procedure was developed to prepare 8-substituted 3,7-dihydropurine-2,6-dione (xanthine) derivatives. 8-Halogen-substituted xanthines were reacted with phenyl- and styrylboronic acids. The best results were obtained using tetrakis(triphenylphosphine)palladium(0) and tripotassium phosphate in dimethylformamide. The developed procedure allows for a convergent synthesis of pharmacologically active 8-substituted xanthine derivatives.
- Vollmann, Karl,Mueller, Christa E.
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p. 871 - 879
(2007/10/03)
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- Synthesis and structure-activity relationships of 3,7-dimethyl-1- propargylxanthine derivatives, A(2A)-selective adenosine receptor antagonists
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A series of 8-substituted derivatives of 3,7-dimethyl-1- propargylxanthine (DMPX) was synthesized and investigated as A(2A) adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored.
- Müller, Christa E.,Geis, Uli,Hipp, Jo,Schobert, Ulrike,Frobenius, Wolfram,Paw?owski, Maciej,Suzuki, Fumio,Sandoval-Ramírez, Jesús
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p. 4396 - 4405
(2007/10/03)
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- Reactions of some 8-diazoxanthine derivatives
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The coupling reaction of 8-diazo-1,3-dimethyl-(3) and 8-diazo-3-methyl-(4)-xanthines with some active methylene compounds does not give the triazine derivative (5); however, it gives new 8-azoxanthine derivatives (6-16).Nevertheless, compounds 3 and 4 undergo coupling reaction with secondary amines producing novel triazene derivatives (17-21).Heating of 3 with some dipolarophiles in benzene affords the unexpected 8-phenyltheophylline (24), which can be methylated to 8-phenylcaffeine (25). 8-Diazotheophylline (3) has been converted into 8-methoxy- and 8-ethoxy-theophyllines (26) and (27) by reaction with MeOH and EtOH, respectively.The reaction of 3 with 10percent HCl produces 8-chlorotheophylline (28).Structures of the compounds have been estabilished by elemental analyses and spectral data.
- Mosselhi, Mosselhi A N,Abbass, Ikhlass M,Abdalla, Magda A,El-Damaty, Allia A
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p. 236 - 242
(2007/10/02)
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- 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: Potent Water-Soluble Antagonistst for A1- and A2-Adenosine Receptors
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A series of 8-(substituted phenyl) derivatives of Theophylline and other 1,3-dialkylxanthines were evaluated for potency and selectivity as antagonists at A1- and A2-adenosine receptors in brain tissue.Theophylline has a similar pote
- Daly, J.W.,Padgett, W.,Shamim, M.T.,Butts-Lamb, P.,Waters, J.
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p. 487 - 492
(2007/10/02)
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- Known and New Types of Reactions in the Photoreaction of Stilbenes with Cyclic Imines
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The photoreactions of stilbene and 1,4-diphenyl-1,3-butadiene with caffeine and of stilbene with benzothiazole, 1-methylimidazole and 2-(methylthio)benzothiazole have been investigated with respect to know (- , -cycloaddition , inserting -addition ), mechanistically new (uncatalyzed, substitutive -addition ) and principally new reaction types (substitutive -addition with substituent migration and cleavage of a double bond , substitutive -addition with cleavage of a double bond , intermolecular exchange of vinyl substituents ).The products are isolated and characterized analytically, spectroscopically (UV, 1H, 13C NMR) and by chemical transformations .The new reaction types are without precedence.They are formulated to occur via 1,4-diradicals.
- Kaupp, Gerd,Grueter, Heinz-Willi
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p. 2844 - 2858
(2007/10/02)
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