- Direct aerobic oxidation of 2-benzylpyridines in a gas-liquid continuous-flow regime using propylene carbonate as a solvent
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The use of high-temperature/pressure gas-liquid continuous flow conditions dramatically enhances the iron-catalyzed aerobic oxidation of 2-benzylpyridines to their corresponding ketones. Pressurized air serves as a readily available oxygen source and propylene carbonate as a green solvent in this radically intensified preparation of synthetically valuable 2-aroylpyridines.
- Pieber, Bartholomaeus,Kappe, C. Oliver
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- Acylation of 2-benzylpyridine N-oxides and subsequent in situ [3,3]-sigamatropic rearrangement reaction
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An effective method for the acylation of 2-benzylpyridine N-oxides and their fast in situ [3,3]-sigmatropic rearrangement was reported. This transformation has a wide substrate scope under mild conditions, giving moderate to excellent yields. The application for the synthesis of chiral phenyl-2-pyridylmethanol products was briefly explored. Furthermore, an interesting example of tandem substitution and in situ [3,3]-sigamatropic rearrangement of 2-benzylpyridine N-oxide with benzenecarboximidoyl chloride was reported.
- Antilla, Jon C.,Jing, Hua-qing,Li, Hong-liang
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- Heteroleptic Ni(II) Complexes Bearing a Bulky Yet Flexible IBiox-6 Ligand: Improved Selectivity in Cross-Electrophile Coupling of Benzyl Chlorides with Aryl Chlorides/Fluorides
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A bisoxazoline-derived NHC known as IBiox-6 reacted smoothly with Ni[P(OEt)3]2Br2 and Ni(PPh3)2Br2 to give the respective heteroleptic Ni(II) complexes Ni(IBiox-6)[P(OEt)3]Br2 (1) and Ni(IBiox-6)(PPh3)Br2 (2) in yields of 60% and 71%. Their crystal structures were characterized to reveal a rare cis disposition of the IBiox-6 ligand to the phosphite ligand in 1, while 2 possessed the more common trans configuration. Both complexes catalyzed the cross-electrophile coupling of benzyl chlorides with aryl chlorides and fluorides in the presence of Mg turnings at 50 °C via a "real one-pot"procedure, featuring no requirement for temperature variation or portionwise addition of any coupling partner. In particular, complex 1 showed a better balance between the catalytic activity and selectivity. The scope of the procedure catalyzed by 1 and Mg turnings was investigated, providing a highly selective, simple, and practical approach to the synthesis of diarylmethanes with high steric hindrance and various functional groups, including oligo-diarylmethane with asymmetric structures.
- Shen, Zheng-Wang,Meng, Die-Die,Imran, Sajid,Yan, Chun-Hui,Sun, Hong-Mei
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supporting information
p. 3540 - 3545
(2020/10/09)
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- Ligand-Free Iridium-Catalyzed Dehydrogenative ortho C?H Borylation of Benzyl-2-Pyridines at Room Temperature
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A convenient and ligand-free iridium-catalyzed dehydrogenative ortho C?H borylation of benzyl-2-pyridines has been developed. The reaction proceeds smoothly at room temperature using pinacolborane as a borylating reagent in the presence of catalytic amount of [IrOMe(COD)]2. The reaction is compatible with many functional groups, providing a vast array of ortho borylated products in moderate to excellent yields with excellent selectivities. (Figure presented.).
- Yang, Yuhuan,Gao, Qian,Xu, Senmiao
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p. 858 - 862
(2019/01/04)
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- Metal-Free Halogen(I) Catalysts for the Oxidation of Aryl(heteroaryl)methanes to Ketones or Esters: Selectivity Control by Halogen Bonding
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Metal-free halogen(I) catalysts were used for the selective oxidation of aryl(heteroaryl)methanes [C(sp3)?H] to ketones [C(sp2)=O] or esters [C(sp3)?O]. The synthesis of ketones was performed with a catalytic amount of NBS in DMSO solvent. Experimental studies and density functional theory (DFT) calculations supported the formation of halogen bonding (XB) between the heteroarene and N-bromosuccinimide, which enabled imine–enamine tautomerism of the substrates. No additional activator was required for this crucial step. Isotope-labeling and other supporting experiments suggested that a Kornblum-type oxidation with DMSO and aerobic oxygenation with molecular oxygen took place simultaneously. A background XB-assisted electron transfer between the heteroarenes and halogen(I) catalysts was responsible for the formation of heterobenzylic radicals and, thus, the aerobic oxygenation. For selective acyloxylation (ester formation), a catalytic amount of iodine was employed with tert-butyl hydroperoxide in aliphatic carboxylic acid solvent. Several control reactions, spectroscopic studies, and Time-Dependent Density Functional Theory (TD–DFT) calculations established the presence of acetyl hypoiodite as an active halogen(I) species in the acetoxylation process. With the help of a selectivity study, for the first time we report that the strength of the XB interaction and the frontier orbital mixing between the substrates and acyl hypoiodites determined the extent of the background electron-transfer process and, thus, the selectivity of the reaction.
- Guha, Somraj,Sekar, Govindasamy
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supporting information
p. 14171 - 14182
(2018/09/10)
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- Photocatalyzed ortho-Alkylation of Pyridine N-Oxides through Alkene Cleavage
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A photocatalyzed reaction of pyridine N-oxides with alkenes gives ortho-alkylated pyridines with cleavage of the carbon–carbon double bond. Benzyl and secondary alkyl groups are incorporated at the ortho position of pyridines in one pot.
- Zhou, Wang,Miura, Tomoya,Murakami, Masahiro
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p. 5139 - 5142
(2018/05/30)
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- Copper-Catalyzed Base-Controlled Diastereoselective Synthesis of Tetraarylethanes from 2-Benzylpyridines
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A highly efficient and base-controlled diastereoselective synthesis of tetraarylethanes through copper-catalyzed dehydrogenative homocoupling of readily available 2-benzylpyridines is reported. Various dl - and meso -tetraarylethanes were diastereoseletively synthesized by this new protocol, where base plays the role of the principle modulator: Grignard reagents selectively provide the C2 isomers, whereas KO t -Bu promotes the formation of the meso -tetraarylethanes. Interestingly, the presence of excess KO t -Bu generates the (E)-tetraarylethenes as the only product.
- Chandrasekar, Selvaraj,Karthikeyan, Iyyanar,Sekar, Govindasamy
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p. 1275 - 1283
(2017/12/26)
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- Efficient Selenium-Catalyzed Selective C(sp3)?H Oxidation of Benzylpyridines with Molecular Oxygen
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An efficient selenium-catalyzed direct oxidation of benzylpyridines in aqueous DMSO has been successfully developed by using molecular oxygen as the oxidant. A variety of benzoylpyridines with broad functional group tolerance were obtained in modest to excellent yields and with exclusive chemoselectivity. (Figure presented.).
- Jin, Weiwei,Zheng, Poonnapa,Wong, Wing-Tak,Law, Ga-Lai
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supporting information
p. 1588 - 1593
(2017/05/05)
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- Direct Triflylation of Benzylic C—H Bonds with Pyridine as a Directing Group
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The first example of benzylic C—H triflylation was accomplished with pyridine as a directing group. The reaction of various 2-benzylpyridines and (CF3SO2)2O in the presence of NEt3 in CH2Cl2 proceeded smoothly to afford the corresponding benzyl triflones in moderate to high yields.
- Yang, Jun,Hu, Juanjuan,Huang, Yangen,Xu, Xiuhua,Qing, Fengling
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supporting information
p. 867 - 870
(2017/06/27)
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- Versatile C(sp2)?C(sp3) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes
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The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross-couplings, and circumvents common issues associated with proto-demetalation and β-hydride elimination.
- Dean, William M.,?iau?iulis, Mindaugas,Storr, Thomas E.,Lewis, William,Stockman, Robert A.
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p. 10013 - 10016
(2016/08/16)
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- Synergistic H4NI-AcOH Catalyzed Oxidation of the Csp3-H Bonds of Benzylpyridines with Molecular Oxygen
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The oxidation of benzylpyridines forming benzoylpyridines was achieved based on a synergistic H4NI-AcOH catalyst and molecular oxygen in high yield under solvent-free conditions. This is the first nonmetallic catalytic system for this oxidation transformation using molecular oxygen as the oxidant. The catalytic system has a wide scope of substrates and excellent chemoselectivity, and this procedure can also be scaled up. The study of a preliminary reaction mechanism demonstrated that the oxidation of the Csp3-H bonds of benzylpyridines was promoted by the pyridinium salts formed by AcOH and benzylpyridines. The synergistic effect of H4NI-AcOH was also demonstrated by control experiments. (Figure Presented).
- Ren, Lanhui,Wang, Lianyue,Lv, Ying,Li, Guosong,Gao, Shuang
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supporting information
p. 2078 - 2081
(2015/05/13)
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- Synthesis of heteroaryl compounds through cross-coupling reaction of aryl bromides or benzyl halides with thienyl and pyridyl aluminum reagents
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An efficient method for synthesis of useful biaryl building blocks containing 2-thienyl, 3-thienyl, 2-pyridyl, and 3-pyridyl moieties was provided through cross-coupling reactions of aryl bromides or benzyl halides with heteroaryl aluminum reagents in the presence of Pd(OAc)2 and (o-tolyl)3P. The coupling reaction also worked efficiently with heteroaryl bromides affording series of heterobiaryl compounds. The reaction of phenylbromide with in situ prepared 3-pyridyl aluminum was demonstrated to afford the product 8a in high yield. Additionally, the catalytic system was also suited well for the coupling reaction of benzyl halides with pyridyl aluminum reagents to afford series of pyridyl-arylmethane.
- Chen, Xu,Zhou, Lingmin,Li, Yimei,Xie, Tao,Zhou, Shuangliu
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p. 230 - 239
(2014/01/17)
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- Synthesis of aryl(di)azinyl ketones through copper- and iron-catalyzed oxidation of the methylene group of aryl(di)azinylmethanes
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Sustainable Oxidations: An oxidation method to transform aryl(di)azinylmethanes into aryl(di)azinyl ketones is described. Base metals (copper and iron) as catalysts in combination with O2 as the oxidant are used, which makes this method sustainable. The utility of this method is illustrated by the synthesis of 6-(4-methylbenzoyl)pyridine-2-carbaldehyde, which is an intermediate in the preparation of the drug Acrivastine. Copyright
- De Houwer, Johan,Abbaspour Tehrani, Kourosch,Maes, Bert U. W.
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supporting information; experimental part
p. 2745 - 2748
(2012/04/10)
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- Palladium-catalyzed decarboxylative couplings of 2-(2-Azaaryl)acetates with aryl halides and triflates
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Pd-catalyzed decarboxylative cross-couplings of 2-(2-azaaryl)acetates with aryl halides and triflates have been discovered. This reaction is potentially useful for the synthesis of some functionalized pyridines, quinolines, pyrazines, benzoxazoles, and benzothiazoles. Theoretical analysis shows that the nitrogen atom at the 2-position of the heteroaromatics directly coordinates to Pd(II) in the decarboxylation transition state.
- Shang, Rui,Yang, Zhi-Wei,Wang, Yan,Zhang, Song-Lin,Liu, Lei
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supporting information; experimental part
p. 14391 - 14393
(2010/12/19)
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- Site-selective sp2 and benzylic sp3 palladium-catalyzed direct arylation
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Palladium-catalyzed site selective arylation reactions of both sp2 and benzylic sp3 sites on azine and diazine N-oxide substrates are described that occur in good to excellent yield and with complete selectivity for reaction at the desired position. These studies have uncovered the need to properly control the metal to ligand ratio in sp2 arylation and necessitated a complete reinvestigation of all reaction parameters for sp3 arylation. From these studies, the choice of base emerged as a pivotal component for site selectivity, pointing to its intimate involvement in the mechanism of direct arylation. These site selective reactions have been validated in both divergent and sequential derivatizations of heterocyclic compounds represent an attractive alternative to other routes to this class of molecule. Copyright
- Campeau, Louis-Charles,Schipper, Derek J.,Fagnou, Keith
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p. 3266 - 3267
(2008/10/09)
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- Convenient, benign and scalable synthesis of 2- and 4-substituted benzylpiperidines
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A short, scalable and environmentally benign synthesis of 2- and 4-substituted benzylpiperidines has been developed. The method is based on the temperature-programmed consecutive deoxygenation and heteroaromatic ring saturation of aryl(pyridin-2-yl)- and aryl(pyridin-4-yl)methanols and aryl(pyridin-4-yl)methanones in the presence of Pd/C catalyst. The crucial roles of the temperature, the acidity and the substrate structure in the change of selectivity have been demonstrated by isolation of several substituted aryl(piperidine)methanols. The carbinols and ketones were prepared from commercially available pyridinecarbaldehydes or 4-cyanopyridine and substituted bromobenzenes via organometallic intermediates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Agai, Bela,Proszenyak, Agnes,Tarkanyi, Gabor,Vida, Laszlo,Faigl, Ferenc
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p. 3623 - 3632
(2007/10/03)
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- LIGAND COUPLING REACTION ON THE PHOSPHORUS ATOM
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Phosphine oxides bearing two or three 2-pyridyl groups were found to react with organometallic compounds affording 2,2'-bipyridyl, 2-substituted pyridines and pyridine in substantial yields.Both ligand exchange and ligand coupling appear to take place within the penta-coordinated phosphorus intermediates formed incipiently.
- Uchida, Yuzuru,Onoue, Katsumi,Tada, Nobuaki,Nagao, Fumio
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p. 567 - 570
(2007/10/02)
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- SENSITIVE NATURE OF LIGAND COUPLING AND PSEUDOROTATION TO ELECTRONIC EFFECT OF SUBSTITUENT---LIGAND COUPLING IN THE REACTIONS OF BENZYLIC ARYL SULFOXIDES WITH BENZYLIC GRIGNARD REAGENTS
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Unlike the reaction of benzylic 2-pyridyl sulfoxides with benzylic Grignard reagents, in the reaction of p-benzenesulfonylphenyl benzylic sulfoxides with benzylic Grignard reagents, benzylic groups bearing an electronwithdrawing group tends to couple with the aryl group preferentially.This change is considered to be due to a slight change of electronic environements which would effect on the ease of pseudorotation of the incipient ?-sulfurane formed during the reaction.
- Wakabayashi, Shoji,Ishida, Masahiro,Takeda, Takashi,Oae, Shigeru
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p. 4441 - 4444
(2007/10/02)
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- Ligand Coupling within ?-Sulphurane Intermediates formed in the Reaction of Benzyl 2-Pyridyl and Related Sulphoxides with Grignard reagents
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The reaction of benzyl or 1-phenylethyl 2-pyridyl sulphoxide (1) or (18) with a Grignard reagent was found to give the ligand-coupling product, i.e., 2-benzylpyridine or 2-(1-phenylethyl)pyridine (2) or (22) in excellent yield.This coupling reaction was found to proceed whithin the ?-sulphurane formed as an intermediate upon treatment of benzyl 2-pyridyl and related sulphoxides with a Grignard reagent.The stereochemical course of this coupling reaction involves complete retention at the benzylic carbon.
- Oae, Shigeru,Kawai, Tsutomu,Furukawa, Naomichi,Iwasaki, Fujiko
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p. 405 - 412
(2007/10/02)
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- LIGAND COUPLING AND PSEUDOROTATION IN THE REACTION OF ALKYL 2-PYRIDYL SULFOXIDE WITH GRIGNARD REAGENTS
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In the reaction of benzyl 2-pyridyl sulfoxide (1) with C6H5CH2MgCl, the incoming Grignard reagent tends to couple preferentially with 2-pyridyl group at lower temperatures, whereas, at higher temperatures, coupling between benzyl and 2-pyridyl groups with 1 tends to increase due presumably to the relatively more facile pseudorotation at higher temperatures.
- Oae, Shigeru,Takeda, Takashi,Kawai, Tsutomu,Furukawa, Naomichi
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p. 133 - 138
(2007/10/02)
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- 1-Acyl-4-alkylidene-1,4-dihydropyridines, 7. Activation with Boron Trifluoride: Intermolecular Acyl Group Transfer and Formation of 1-(4-Pyridyl)-2-alkanones
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1-Acyl-4-alkylidene-1,4-dihydropyridines 5, representatives of the thermally stable enamides, can be activated by means of boron trifluoride 6, so the ketones 7 result from attack of 6 on 5 (intermolecular acyl group transfer).The mechanism of this reaction, which has not previously been observed for enamides, is strongly suggested to be as follows: 5 and 6 form first the adduct 21, which attacks 5 with formation of 27.Special examples of 5 (11 and 12) are found to be reactive enough that the ketone 7h or the sulfone 15 can be obtained from their isolable precursors (14 and 13) without Lewis-acid activation. 13 is particularly noteworthy: being the precursor of the salt 16, which is generated in situ, it serves as an extremely effective tosylating agent.Even tertiary alcohols are attackted by 16.
- Anders, Ernst,Will, Wolfgang,Stankowiak, Achim
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p. 3192 - 3204
(2007/10/02)
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- Flash Vacuum Pyrolysis of Substituted Pyridine N-Oxides and Its Application to Syntheses of Heterocyclic Compounds
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Flash vacuum pyrolysis of 2-picoline N-oxide gave 2-picoline, pyridine, 2-ethylpyridine, 2-vinylpyridine, 2-pyridylmethanol, bis(2-pyridyl)methane, 1,2-bis(2-pyridyl)ethane, and 1,2-bis(2-pyridyl)ethylene.These reactions are explained by intermediary participation of the 2-picolyl radical.Flash vacuum pyrolysis of methyl-substituted 2-benzylpyridine N-oxides led to methyl-substituted pyridoindoles or to benzoquinoline in moderate yields.
- Ohsawa, Akio,Kawaguchi, Takayuki,Igeta, Hiroshi
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p. 3497 - 3503
(2007/10/02)
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