- Synthetic method of N - aryl substituted lactam compound
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The invention discloses a method. NSynthesis method of - aryl substituted lactam compound, and synthesis method thereof is promoted by tertiary butyl hydroperoxide and-tert-butyl hydroperoxideNMulti-step series reaction synthesis - aryl substituted saturated cyclic amine compoundN- Aryl substituted lactam compounds are simple and convenient to operate. The method has the advantages of no transition metal catalysis, wide substrate application range and the like, and is suitable for industrial production.
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Paragraph 0047-0049
(2021/08/25)
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- Amidation of Aryl Chlorides Using a Microwave-Assisted, Copper-Catalyzed Concurrent Tandem Catalytic Methodology
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A concurrent tandem catalytic (CTC) methodology has been developed for the amidation of aryl chlorides where the aryl chloride is first converted to an aryl iodide via halogen exchange and the aryl iodide is subsequently transformed into the aryl amide. A variety of aryl chlorides were converted to aryl amides in up to 85% isolated yield using 20 mol % CuI, 60 mol % N,N′-cyclohexane-1,2-diamine, 2.2 equiv of K2CO3, and 1.05-1.5 equiv of amide in acetonitrile at 200 °C after 0.75-1 h. The same copper/ligand system served as multifunctional catalyst for both steps of the concurrent catalytic process with iodide present in substoichiometric amounts. Mechanistic studies were consistent with CTC amidation occurring via a nonradical mechanism. Kinetic modeling was conducted to investigate the effect of competitive direct amidation of an aryl chloride or aryl bromide on the formation of product over time during a CTC amidation reaction.
- Chang, Raymond K.,Clairmont, Brice P.,Lin, Shirley,MacArthur, Amy H. Roy
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supporting information
p. 4448 - 4454
(2019/11/13)
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- Ligand-Enabled Gold-Catalyzed C(sp2)-N Cross-Coupling Reactions of Aryl Iodides with Amines
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The first example of ancillary (P,N)-ligand-enabled gold-catalyzed C-N cross-coupling reactions of aryl iodides with amines is reported. The high generality of the reaction in de novo synthesis, late-stage modifications, and cascade processes to access functionalized indolinones and carbazoles underscores the synthetic potential of the presented strategy. Monitoring the reaction with ESI-HRMS and NMR provided strong evidence for the in situ formation of putative high valent Au(III) intermediates.
- Akram, Manjur O.,Das, Avishek,Chakrabarty, Indradweep,Patil, Nitin T.
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supporting information
p. 8101 - 8105
(2019/10/11)
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- PIFA-Promoted, Solvent-Controlled Selective Functionalization of C(sp2)-H or C(sp3)-H: Nitration via C-N Bond Cleavage of CH3NO2, Cyanation, or Oxygenation in Water
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A novel nitration (via C(sp3)-N breaking/C(sp2)-N formation with CH3NO2) mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA) is described. The NO2 transfer from CH3NO2 to the aromatic group of the substrate is possible with careful selection of the solvent, NaX, and oxidant. In addition, the solvent-controlled C(sp2)-H functionalization can shift to an α-C(sp3)-H functionalization (cyanation or oxygenation) of the α-C(sp3)-H of cyclic amines.
- Mudithanapelli, Chandrashekar,Dhorma, Lama Prema,Kim, Mi-Hyun
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- Selective synthesis of pyrrolidin-2-ones and 3-iodopyrroles: Via the ring contraction and deformylative functionalization of piperidine derivatives
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In this paper, a selective synthesis of pyrrolidin-2-ones and 3-iodopyrroles via the cascade reactions of N-substituted piperidines is presented. Mechanistically, the formation of pyrrolidin-2-ones involves a domino process including the in situ formation of pyrrolidine-2-carbaldehyde followed by carboxylic acid formation, decarboxylation and ipso-oxidation. On the other hand, 3-iodopyrroles are believed to be formed via the initial generation of pyrrolidine-2-carbaldehyde followed by carboxylic acid formation, decarboxylation, dehydrogenation, iodination and aromatization. Interestingly, either pyrrolidin-2-ones or 3-iodopyrroles could be obtained selectively from the same substrates, and the selectivity was easily tuned by using a specific oxidant and additive.
- Wang, Fang,Zhang, Xinying,He, Yan,Fan, Xuesen
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p. 156 - 164
(2019/01/08)
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- Pyrrolidone compound synthesis method
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The invention discloses a pyrrolidone compound synthesis method, and belongs to the technical field of organic synthesis. Saturated cyclic tertiary amine 1 is added into solvents, and heating reactionis performed in the presence of oxidizing agent, cupric salt, potassium hydrogen persulfate compound salt (Oxone) and oxygen mixture, additives, elementary iodine or iodated metal salt and the like to obtain pyrrolidone 2. According to the method, a pyrrolidone compound is synthesized by cascade reaction of oxidization retraction, decarbonylation and in-situ oxidization of saturated cyclic tertiary amine compounds, the method has the advantages of simplicity and convenience in operation, mild conditions, wide substrate application range and the like, and an economical, practical, green and environment-friendly novel method is provided for synthesis of the pyrrolidone compound.
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Paragraph 0054-0056
(2019/03/08)
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- Ruthenium-catalyzed synthesis of: N -substituted lactams by acceptorless dehydrogenative coupling of diols with primary amines
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Herein, we report the first example of synthesis of N-substituted lactams via an acceptorless dehydrogenative coupling of diols with primary amines in one step, which was enabled by combining Ru3(CO)12 with a hybrid N-heterocyclic carbene-phosphine-phosphine ligand as the catalyst.
- Zheng, Yanling,Nie, Xufeng,Long, Yang,Ji, Li,Fu, Haiyan,Zheng, Xueli,Chen, Hua,Li, Ruixiang
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p. 12384 - 12387
(2019/10/19)
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- Aluminium Chloride-Mediated Synthesis of 1-Chloro-2,2,2-Trifluoroethylidene-Substituted Pyrrolidones
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An aluminium chloride-mediated cascade reaction between pyrrolidones and trifluoroacetic anhydride is reported. Functionally diverse 1-chloro-2,2,2-trifluoroethylidene-substituted pyrrolidones were obtained in moderate to high yields through electrophilic trifluoroacetylation, nucleophilic chlorination, and elimination. This procedure has a wide scope, good functional-group tolerance and the reaction conditions are amenable to scale up. Additionally the obtained 1-chloro-2,2,2-trifluoroethylidene products can be applied to further functionalization as trifluoromethyl-containing building blocks. Some of the title compounds showed fungicidal activity against cucumber downy mildew (CDM). (Figure presented.).
- Wang, Zeng,Yuan, Zihang,Han, Xiaoyan,Weng, Zhiqiang
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supporting information
p. 2178 - 2182
(2018/04/25)
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- Copper-Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amides
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Cu2O/N,N′-bis(thiophen-2-ylmethyl)oxalamide is established to be an effective catalyst system for Goldberg amidation with inferior reactive (hetero)aryl chlorides, which have not been efficiently documented by Cu-catalysis to date. The reaction is well liberalized toward a variety of functionalized (hetero)aryl chlorides and a wide range of aromatic and aliphatic primary amides in good to excellent yields. Furthermore, the arylation of lactams and oxazolidinones is achieved. The present catalytic system also accomplished an intramolecular cross-coupling product.
- De, Subhadip,Yin, Junli,Ma, Dawei
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supporting information
p. 4864 - 4867
(2017/09/23)
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- Efficient Synthesis of N-Substituted 2,4-Azepandione Ring System as an Active Intermediate for Heterocyclic Syntheses
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An improved efficient synthesis for 2,4-azepandiones (3, 8, and 14) could be achieved by a careful control of the reaction conditions to cyclize ethyl 4-(N-acetylarylamino) butanoate (1, 7, and 13), respectively. The ethyl 4-arylamino butanoate (9 or 12) was prepared by stirring the ethyl 4-bromobutanoate and substituted anilines at room temperature. Then, they were acetylated with acetyl chloride and triethylamine under the conditions that avoid the formation of 2-pyrrolidinone derivatives 10. Due to the rapid decomposition of the acetylated product (7 or 13) to its starting material (9 or 12), the reaction mixture is directly transferred without workup to the next cyclization step. The azepandione synthesis is favored by using a weak base at low temperature, where it is in a competition with the other modes of ring closure. The structures of the new compounds were supported by correct analytical and spectral data.
- Waly, Mohamed A.,Yossif, Shiam A.,Ibrahim, Ismail T.,Sofan, Mamdouh A.
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p. 1318 - 1326
(2017/03/27)
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- Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under electron ionization and in the condensed phase
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Rationale: Mass spectrometry is known as an excellent method to predict the behavior of organic compounds in solution. The behavior of organic compounds in the gas phase inside the ion source of a mass spectrometer allows their intrinsic properties to be defined, avoiding the influence of intermolecular interactions, counter ions and solvent effects. Methods: Arylpyrrolidin-2-ones were obtained by condensed-phase synthesis from the corresponding N-arylcyclopropanecarboxamides. Electron ionization (EI) with accurate mass measurements by high-resolution time-of-flight mass-spectrometry and quantum chemical calculations were used to understand the behavior of the molecular radical cations of N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones in the ion source of a mass spectrometer. The geometries of the molecules, transition states, and intermediates were fully optimized using DFT-PBE calculations. Results: Fragmentation schemes, ion structures, and possible mechanisms of primary isomerisation were proposed for isomeric N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones. Based on the fragmentation pattern of the N-arylcyclopropanecarboxamides, isomerisation of the original M+? ions into the M+? ions of the N-arylpyrrolidin-2-ones was shown to be only a minor process. In contrast, this cyclization proceeds easily in the condensed phase in the presence of Br?nsted acids. Conclusions: Based on the experimental data and quantum chemical calculations the principal mechanism of decomposition of the molecular ions of N-arylcyclopropanecarboxamides involves their direct fragmentation without any rearrangements. An alternative mechanism is responsible for the isomerisation of a small portion of the higher energy molecular ions into the corresponding N-arylpyrrolidin-2-one ions. Copyright
- Lebedev, A. T.,Mazur, D. M.,Kudelin, A. I.,Fedotov, A. N.,Gloriozov, I. P.,Ustynyuk, Yu. A.,Artaev, V. B.
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p. 2416 - 2422
(2016/10/22)
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- Mild and Efficient Cobalt-Catalyzed Cross-Coupling of Aliphatic Amides and Aryl Iodides in Water
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A convenient protocol for the C-N cross-coupling of aliphatic amides and iodobenzene is demonstrated using a simple and inexpensive Co(C2O4)·2H2O/N,N′-dimethylethylenediamine (DMEDA) catalytic system in water. Good yields of N-arylated products were isolated (up to 85%) and the protocol has been successfully applied to the synthesis of the anticancer drug, flutamide.
- Tan, Bryan Yong-Hao,Teo, Yong-Chua
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supporting information
p. 1697 - 1701
(2015/07/20)
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- Cycloaddition of Enamine and Iminium Ion Intermediates Formed in the Reaction of N -Arylpyrrolidines with T-HYDRO
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The reaction of N-arylpyrrolidine derivatives with 70% aqueous tert-butyl hydroperoxide (T-HYDRO) in the presence of NaOAc·3H2O gives tetracyclic amines in 59-78% yields via cycloaddition of the corresponding iminium ion and enamine intermediates formed in situ in cyclohexane solvent. The iminium ion intermediate reacts with t-BuOK in methanol to give the corresponding cyclic amides in 85-88% yields or undergoes alkylation to give the corresponding nitromethyl product in 74-79% yields using t-BuOK and nitromethane in methanol.
- Rao, Gunda Ananda,Periasamy, Mariappan
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p. 2231 - 2236
(2015/09/28)
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- Selective copper-catalyzed N-arylation of lactams with arylboronic acids under base- and ligand-free conditions
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An oxidative copper-catalyzed cross-coupling of arylboronic acids with various ring-size lactams has been developed. The N-arylated lactams were obtained in moderate to excellent yields without any additional bases, ligands, or additives. This reaction shows complete selectivity for N-arylation of lactams in the presence of a hydroxyl group.
- Bathini, Thulasiram,Rawat, Vikas Singh,Sreedhar, Bojja
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supporting information
p. 1348 - 1351
(2015/06/16)
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- Ligand-free Ullmann-type C-heteroatom couplings under practical conditions
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A new practical ligand-free protocol for copper-catalyzed C-heteroatom cross-coupling reactions (Ullmann-type) is described. The use of dimethyl sulfoxide (DMSO) as the solvent overcomes the need to use organic auxiliary ligands; thus, DMSO is revealed as a nontoxic and superior solvent for Ullmann-type coupling reactions. This method allows the arylation of a wide range of amides, alcohols, and amines under practical conditions with bromobenzene and iodobenzene derivatives and will likely find direct application in current organic synthesis. The competitive reactivity among different functional groups is reported and rationalized, and the possibility to achieve selective arylation reactions is demonstrated. Copyright
- Gueell, Imma,Ribas, Xavi
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p. 3188 - 3195
(2014/06/09)
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- Heterogeneous CuII-catalysed solvent-controlled selective N-arylation of cyclic amides and amines with bromo-iodoarenes
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A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalysed by CuII/Al2O3 has been achieved. This protocol has been employed for the synthesis of a library of arenes bearing a cyclic amide and an amine moiety at two ends, including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry (ICP-MS) studies of the catalyst at different stages of the reaction. The CuII/Al2O 3 catalyst was recovered and recycled for subsequent reactions. One over the other: A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalyzed by CuII/Al2O3 has been achieved (see scheme). This protocol has been employed for the synthesis of a library of arenes bearing cyclic amide and amine moieties at two ends including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed spectroscopic studies (FG=functional group). Copyright
- Kundu, Debasish,Bhadra, Sukalyan,Mukherjee, Nirmalya,Sreedhar, Bojja,Ranu, Brindaban C.
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p. 15759 - 15768
(2013/11/19)
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- Copper(I) complexes with trispyrazolylmethane ligands: Synthesis, characterization, and catalytic activity in cross-coupling reactions
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Three novel Cu(I) complexes bearing tris(pyrazolyl)methane ligands, Tpmx, have been prepared from reactions of equimolar amounts of CuI and the ligands Tpm, (HC(pz)3), Tpm, (HC(3,5-Me2-pz) 3), and TpmMs, (HC(3-Ms-pz)3). X-ray diffraction studies have shown that the Tpm and TpmMs derivatives exhibit a 2:1 Cu:ligand ratio, whereas the Tpm* complex is a mononuclear species in nature. The latter has been employed as a precatalyst in the arylation of amides and aromatic thiols with good activity. The synthesis of a TpmCu(I)-phthalimidate, a feasible intermediate in this catalytic process, has also been performed. Low temperature 1H NMR studies in CDCl 3 have indicated that this complex exists in solution as a mixture of two, neutral and ionic forms. Conductivity measurements have reinforced this proposal, the ionic form predominating in a very polar solvent such as DMSO. The reaction of TpmCu(I)-phthalimidate with iodobenzene afforded the expected C-N coupling product in 76% yield accounting for its role as an intermediate in this transformation.
- Haldon, Estela,Alvarez, Eleuterio,Nicasio, M. Carmen,Perez, Pedro J.
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experimental part
p. 8298 - 8306
(2012/09/22)
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- Copper-catalyzed N-arylation of amides using (S)-N-methylpyrrolidine-2- carboxylate as the ligand
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(S)-N-methylpyrrolidine-2-carboxylate, a derivative of natural L-proline, was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides with aryl halides under mild conditions. A variety of N-arylamides were synthesized in good to high yields.
- Wang, Chaoyu,Liu, Lijuan,Wang, Wei,Ma, Dong-Sheng,Zhang, Hua
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experimental part
p. 1154 - 1160
(2010/06/13)
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- Facile cuI-catalyzed arylation of azoles and amides using simple enaminones as efficient ligands
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(E)-3-(Dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one was found to be an excellent ligand for copper-catalyzed N-arylation of azoles and amides with aryl halides under mild conditions. The reaction took place at 82 C in MeCN with broad functional-group compatibility. A combination of the ligand and CuI proved to be an efficient catalytic system to promote the coupling reactions of aryl halides with azoles and amides.
- Cheng, Cungui,Sun, Gonglei,Wan, Jieping,Sun, Cuirong
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experimental part
p. 2663 - 2668
(2010/01/16)
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- Copper-catalyzed N-arylation of amides and azoles using phosphine-free hydrazone ligands
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Phosphine-free hydrazone such as 1c was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides and Ullmann-type N-arylation of azoles with aryl halides under mild conditions. A variety of N-arylamides and N-arylazoles were synthesized in good to high yields. Georg Thieme Verlag Stuttgart.
- Mino, Takashi,Harada, Yoshikazu,Shindo, Hiroaki,Sakamoto, Masami,Fujita, Tsutomu
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p. 614 - 620
(2008/12/22)
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- Copper complexes of anionic nitrogen ligands in the amidation and imidation of aryl halides
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Copper(I) imidate and amidate complexes of chelating N,N-donor ligands, which are proposed intermediates in copper-catalyzed amidations of aryl halides, have been synthesized and characterized by X-ray diffraction and detailed solution-phase methods. In some cases, the complexes adopt neutral, three-coordinate trigonal planar structures in the solid state, but in other cases they adopt an ionic form consisting of an L2Cu+ cation and a CuX2- anion. A tetraalkylammonium salt of the CuX2- anion in which X = phthalimidate was also isolated. Conductivity measurements and 1H NMR spectra of mixtures of two complexes all indicate that the complexes exist predominantly in the ionic form in DMSO and DMF solutions. One complex was sufficiently soluble for conductance measurements in less polar solvents and was shown to adopt some degree of the ionic form in THF and predominantly the neutral form in benzene. The complexes containing dative nitrogen ligands reacted with iodoarenes and bromoarenes to form products from C-N coupling, but the ammonium salt of [Cu(phth) 2]- did not. Similar selectivities for stoichiometric and catalytic reactions with two different iodoarenes and faster rates for the stoichiometric reactions implied that the isolated amidate and imidate complexes are intermediates in the reactions of amides and imides with haloarenes catalyzed by copper complexes containing dative N,N ligands. These amidates and imidates reacted much more slowly with chloroarenes, including chloroarenes that possess more favorable reduction potentials than some bromoarenes and that are known to undergo fast dissociation of chloride from the chloroarene radical anion. The reaction of o-(allyloxy)iodobenzene with [(phen)2Cu] [Cu(pyrr)2] results in formation of the C-N coupled product in high yield and no detectable amount of the 3-methyl-2,3-dihydrobenzofuran or 3-methylene-2,3-dihydrobenzofuran products that would be expected from a reaction that generated free radicals. These data and computed reaction barriers argue against mechanisms in which the haloarene reacts with a two-coordinate anionic copper species and mechanisms that start with electron transfer to generate a free iodoarene radical anion. Instead, these data are more consistent with mechanisms involving cleavage of the carbon-halogen bond within the coordination sphere of the metal.
- Tye, Jesse W.,Weng, Zhiqiang,Johns, Adam M.,Incarvito, Christopher D.,Hartwig, John F.
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supporting information; body text
p. 9971 - 9983
(2009/02/04)
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- Oxazolidin-2-one-promoted CuI-catalyzed amidation of aryl halides and cyclization of o-halobenzanilides
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Oxazolidin-2-one was found to be a versatile and efficient ligand for the CuI-catalyzed amidation of aryl halides and the cyclization of ortho-halobenzanilides. Notably, the less active halides could also be applied successfully in the synthesis of benzoxazoles and benzothiazoles. Georg Thieme Verlag Stuttgart.
- Heng, Chang Ma,Xuan, Zhen Jiang
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experimental part
p. 1335 - 1340
(2009/04/06)
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- Pd-catalyzed amidations of aryl chlorides using monodentate biaryl phosphine ligands: A kinetic, computational, and synthetic investigation
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We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of κ2- amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the κ2-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.
- Ikawa, Takashi,Barder, Timothy E.,Biscoe, Mark R.,Buchwald, Stephen L.
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p. 13001 - 13007
(2008/09/17)
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- A β-keto ester as a novel, efficient, and versatile ligand for copper(I)-catalyzed C-N, C-O, and C-S coupling reactions
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(Formula Presented) Employing ethyl 2-oxocyclohexanecarboxylate as a novel, efficient, and versatile ligand, the copper-catalyzed coupling reactions of various N/O/S nucleophilic reagents with aryl halides could be successfully carried out under mild conditions. A variety of products including N-arylamides, N-arylimidazoles, aryl ethers, and aryl thioethers were synthesized in good to excellent yields.
- Lv, Xin,Bao, Weiliang
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p. 3863 - 3867
(2008/02/02)
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- Ring-expanding reaction of cyclopropyl amides with triphenylphosphine and carbon tetrahalide
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We succeeded in activating cyclopropyl amides (monoactivated cyclopropane) through the corresponding imidoyl halides prepared in situ in the presence of 2 equiv of PPh3 and 1 equiv of CX4, and the ring-expanding products (N-substituted pyrrolidin-2-ones) were obtained in good yields. The reaction mechanism was investigated on the basis of oxygen-18 tracer experiment.
- Yang, Yong-Hua,Shi, Min
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p. 8645 - 8648
(2007/10/03)
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- Amino acid-mediated Goldberg reactions between amides and aryl iodides
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A highly general, experimentally simple, and inexpensive catalyst system was developed for the amidation of aryl iodides by using 5mol% of CuI as catalyst, 20mol% of an amino acid as ligand, and K3PO4 as base.
- Deng, Wei,Wang, Ye-Feng,Zou, Yan,Liu, Lei,Guo, Qing-Xiang
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p. 2311 - 2315
(2007/10/03)
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- Copper-catalyzed formation of carbon-heteroatom and carbon-carbon bonds
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The present invention relates to copper-catalyzed carbon-heteroatom and carbon-carbon bond-forming methods. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of an amide or amine moiety and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In additional embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between a nitrogen atom of an acyl hydrazine and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In other embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-nitrogen bond between the nitrogen atom of a nitrogen-containing heteroaromatic, e.g., indole, pyrazole, and indazole, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. In certain embodiments, the present invention relates to copper-catalyzed methods of forming a carbon-oxygen bond between the oxygen atom of an alcohol and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. The present invention also relates to copper-catalyzed methods of forming a carbon-carbon bond between a reactant comprising a nucleophilic carbon atom, e.g., an enolate or malonate anion, and the activated carbon of an aryl, heteroaryl, or vinyl halide or sulfonate. Importantly, all the methods of the present invention are relatively inexpensive to practice due to the low cost of the copper comprised by the catalysts.
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- A general and efficient copper catalyst for the amidation of aryl halides
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An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2-10 mol % of Cul, 5-20 mol % of a 1,2-diamine ligand, and K3PO4, K2CO3, or Cs2CO3 as base. Catalyst systems based on N, N′-dimethylethylenediamine or trans-N,N′-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology.
- Klapars, Artis,Huang, Xiaohua,Buchwald, Stephen L.
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p. 7421 - 7428
(2007/10/03)
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- Reformatsky reactions with N-arylpyrrolidine-2-thiones: Synthesis of tricyclic analogues of quinolone antibacterial agents
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A convenient synthesis of 5-oxo-1,2,3,5-tetrahydropyrrolo[1,2-α]quinoline-4-carboxylic acids, tricylic analogues of the quinolone antibiotics, is described. Key steps in the route are a novel zinc-mediated Reformatsky reaction between diethyl bromomalonate and N-arylpyrrolidine-2-thione 18, and cyclisation of the resulting diethyl pyrrolidinylidenemalonate intermediates 19 in polyphosphoric acid. The products proved to be devoid of biological activity.
- Michael, Joseph P,De Koning, Charles B,Hosken, Gladys D,Stanbury, Trevor V
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p. 9635 - 9648
(2007/10/03)
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- Copper-catalyzed N-arylation of amines with hypervalent iodonium salts
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The copper-catalyzed N-arylation of amines with hypervalent iodonium compounds with secondary aliphatic amines, aromatic amines, azoles and amides was accomplished with catalytic CuI (10 mol%) or Cu(acac)2 (5 mol%) in the presence of Na2CO3 or K2CO3 as a base in CH2Cl2 or toluene under mild conditions.
- Kang, Suk-Ku,Lee, Sang-Ho,Lee, Duckhee
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p. 1022 - 1024
(2007/10/03)
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- 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as novel inhibitors of human eosinophil phosphodiesterase
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High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4,5,6,7,- tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 μM. One such compound, CP-220,629 (22) (IC50 = 0.44 μM), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1β (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).
- Duplantier, Allen J.,Andresen, Catharine J.,Cheng, John B.,Cohan, Victoria L.,Decker, Christian,DiCapua, Frank M.,Kraus, Kenneth G.,Johnson, Kerry L.,Turner, Claudia R.,UmLand, John P.,Watson, John W.,Wester, Ronald T.,Williams, Alison S.,Williams, John A.
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p. 2268 - 2277
(2007/10/03)
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- Reaction of β-, γ-, and δ-chloroalkanamides with potassium tert-butoxide in tetrahydrofuran: Elimination, and lactamization
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γ- and δ-Chloroalkanamides were found to undergo lactamization readily when treated with potassium tert-butoxide in tetrahydrofuran. Raising the reaction temperature may encourage SN2 displacement reaction. On the other hand β-chloroalkanamides only undergo elimination, followed by dimerization and trimerization of the acrylamide initially formed.
- Wang, Eng Chi,Lin, Huey-Jen
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p. 481 - 489
(2007/10/03)
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- A versatile synthesis of tricyclic analogues of quinolone antibacterial agents: Use of a novel Reformatsky reaction
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A simple synthesis of tricyclic analogues of the quinolone antibiotics bearing a diverse range of substituents on the aromatic ring is described. The key steps involve unprecedented Reformatsky reaction between diethyl bromomalonate and N-arylpyrrolidine-2-thiones 8, followed by cyclisation of the resulting enaminone intermediates 9 in polyphosphoric acid.
- Michael, Joseph P.,De Koning, Charles B.,Stanbury, Trevor V.
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p. 9403 - 9406
(2007/10/03)
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- Conformational Analysis of Rotational Barriers in N-Arylpyrrolidin-2-ones
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The structures of N-phenylpyrrolidin-2-one and the three isomeric N-tolylpyrrolidin-2-ones have been studied by single-crystal X-ray diffraction, as a basis for the conformational analysis of the barrier to rotation around the single bond between the rings.Force-field simulation of the molecular structure is consistent with a rotational barrier of 7 kJ mol-1.Crystal data: N-phenylpyrrolidin-2-one, orthorhombic, Pbca, a = 14.114 (3), b = 6.879 (4), c = 17.386 (5) Angstroem, R = 0.059 for 1110 unique reflections o4?(Fo)>; N-(2-methylphenyl)pyrrolidin-2-one,orthorhombic, Pbca, a = 16.999 (4), b = 16.411 (2), c = 7.008 (2) Angstroem, R = 0.077 for 1479 unique reflections o4?(Fo)>; N-(3-methylphenyl)pyrrolidin-2-one, monoclinic, P21/c, a = 10.411 (2), b = 7.645 (2), c = 12.782 (1) Angstroem, β = 110.32 (1) deg, R = 0.065 for 1641 unique reflections o4?(Fo)>; N-(4-methylphenyl)pyrrolidin-2-one, orthorhombic, P212121, a = 7.668 (2), b = 10.804 (2), c = 11.456 (1) Angstroem, R = 0.054 for 1155 unique reflections o4?(Fo)>.
- Billing, D. G.,Boeyens, J. C. A.,Denner, L.,Plooy, K. E. Du,Long, G. C.,Michael, J. P.
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p. 284 - 288
(2007/10/02)
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- Kinetics and Equilibria of Ring Closure through an Amide Linkage. Part 2. 1-Aryl-2-pyrrolidones
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Equilibrium constants, and rate constants for forward and reverse reactions, for ring closure of several 4-(arylamino)butanoic acids to 1-aryl-2-pyrrolidones in aqueous acid, together with ionisation constants of the former group of compounds, are reported.The equilibrium constants K at 50 deg C between neutral protonic forms of open-chain and ring compounds are related to the ionisation constants of the nitrogen-protonated 4-(arylamino)butanoic acids, K1, by the equation: log K=0.70 (pK1)+1.53.The value of K for pyrrolidone itself was measured for comparison.Studies of 18O exchange reveal that (except in the case of the substrate which bears the most electron-withdrawing substituents in the aryl ring, namely 2,4-dinitro) the rate-determining step lies between the tetrahedral intermediate and the ring compound.Substituent effects and solvent deuterium isotope effects on the hydronium-ion catalysed reaction are consisitent with a transition state close to the neutral tetrahedral intermediate.The effects of methyl substituents in the heterocyclic ring on rate and equilibrium constants have also been studied.The variation of K with temperature, and derived thermodynamic parameters, are reported in two cases.
- Abdallah, Jassim M.,Moodie, Roy B.
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p. 1243 - 1250
(2007/10/02)
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