- Enantioselective Ni-Catalyzed Electrochemical Synthesis of Biaryl Atropisomers
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A scalable enantioselective nickel-catalyzed electrochemical reductive homocoupling of aryl bromides has been developed, affording enantioenriched axially chiral biaryls in good yield under mild conditions using electricity as a reductant in an undivided cell. Common metal reductants such as Mn or Zn powder resulted in significantly lower yields in the absence of electric current under otherwise identical conditions, underscoring the enhanced reactivity provided by the combination of transition metal catalysis and electrochemistry.
- Chen, Song,Chen, Yue-Gang,Gao, Pei-Sen,Liu, Dong,Ma, Hong-Xing,Mei, Tian-Sheng,Qiu, Hui,Shuai, Bin,Wang, Yun-Zhao
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supporting information
p. 9872 - 9878
(2020/06/27)
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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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supporting information
(2020/09/22)
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- Strategic Approach on N-Oxides in Gold Catalysis – A Case Study
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An extensive kinetic study of selected key reactions of (oxidative) gold catalysis concentrates on the decrease of the catalytic activity due to inhibition of the gold(I) catalyst caused by pyridine derivatives that are obtained as by-products if N-oxides are applied as oxygen donors. The choice of the examined pyridine derivatives and their corresponding N-oxides has been made regardless of their commercial availability; particular attention has been paid to the practical benefit which up to now has been neglected in most of the reaction screenings. The test reactions were monitored by GC and 1H NMR spectroscopy. The received reaction constants provide information concerning a correlation between the electronic structure of the heterocycle and the catalytic activity. Based on the collected kinetic data, it was possible to develop a basic set of three N-oxides which have to be taken into account in further oxidative gold(I)-catalyzed reactions. (Figure presented.).
- Schie?l, Jasmin,Stein, Philipp M.,Stirn, Judith,Emler, Kirsten,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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supporting information
p. 725 - 738
(2018/10/20)
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- 3-OXO-TETRAHYDRO-FURO[3,2-B]PYRROL-4(5H)-YL) DERIVATIVES I
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The invention relates to amidic oxotetrahydro-2H-furo[3.2-b]pyrrol-4(5H)-yl) derivatives as dual CatS/K inhibitors, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 58
(2015/11/16)
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- 3-OXO-TETRAHYDRO-FURO[3,2-B]PYRROL-4(5H)-YL) DERIVATIVES II
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The invention relates to amidic oxotetrahydro-2H-furo[3.2-b]pyrrol-4(5H)-yl) derivatives as dual CatS/K inhibitors exhibiting a pronounced CatK-inhibition, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 32; 33
(2015/12/11)
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- Reversible dioxygen binding and arene hydroxylation reactions: Kinetic and thermodynamic studies involving ligand electronic and structural variations
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Copper-dioxygen interactions are of intrinsic importance in a wide range of biological and industrial processes. Here, we present detailed kinetic/thermodynamic studies on the O2-binding and arene hydroxylation reactions of a series of xylyl-bridged binuclear copper(I) complexes, where the effects of ligand electronic and structural elements on these reactions are investigated. Ligand 4-pyridyl substituents influence the reversible formation of side-on bound μ-η2:η2- peroxodicopper(II) complexes, with stronger donors leading to more rapid formation and greater thermodynamic stability of product complexes [Cu II2(RXYL)(O22-)] 2+. An interaction of the latter with the xylyl π-system is indicated. Subsequent peroxo electrophilic attack on the arene leads to C-H activation and oxygenation with hydroxylated products [CuII 2(RXYLO-)(-OH)]2+ being formed. A related unsymmetrical binucleating ligand was also employed. Its corresponding O2-adduct [CuII2(UN)(O 22-)]2+ is more stable, but primarily because the subsequent decay by hydroxylation is in a relative sense slower. The study emphasizes how ligand electronic effects can and do influence and tune copper(I)-dioxygen complex formation and subsequent reactivity.
- Karlin, Kenneth D.,Zhang, Christiana Xin,Rheingold, Arnold L.,Galliker, Benedikt,Kaderli, Susan,Zuberbühler, Andreas D.
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scheme or table
p. 138 - 150
(2012/08/27)
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- 5-ALKYNYL-PYRIDINES
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The present invention encompasses compounds of general Formula (I), wherein R1 to R4, m and n are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.
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Page/Page column 23-24
(2010/11/05)
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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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- N-oxidation of 2-substituted pyridines and quinolines by dimethyldioxirane: Kinetics and steric effects
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The oxidation of 2-substituted pyridines and selected N-containing aromatic heterocycles by dimethyldioxirane (1) produced the corresponding N-oxides as the sole products, quantitatively in most cases. The second order rate constants for N-oxidation by 1 in dried acetone at 23°C were determined for a series of 2-substituted pyridines 2-10, quinolines 11-14 and isoquinolines 15,16. An excellent correlation of log k2 with Taft (σ*) constants was obtained for 2-substituted pyridines (R = Me, Et, Prn, Pr i, 3-pentyl) with the exception of the data for 2-f-butylpyridine. The results for the substituted quinolines and isoquinolines followed the same trends observed with the pyridines. Steric effects due to 2-substitution and periinteractions can substantially reduce reactivity. The results provide insights into the geometrical requirements for N-oxidation by dimethyldioxirane.
- Winkeljohn, W. Rucks,Leggett-Robinson, Pamela,Peets, Monique R.,Strekowski, Lucjan,Vasquez, Pedro C.,Baumstark
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- Tuning copper-dioxygen reactivity and exogenous substrate oxidations via alterations in ligand electronics
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Copper(I)-dioxygen adducts are important in biological and industrial processes. For the first time we explore the relationship between ligand electronics, CuI-O2 adduct formation and exogenous substrate reactivity. The copper(I) complexes [CuI(R-MePY2)]+ (1R, where R = Cl, H, MeO, Me2N) were prepared; where R-MePY2 are 4-pyridyl substituted bis[2-(2-pyridyl)ethyl]methylamine chelates. Both the redox potential of 1R (ranging from E 1/2 = -270 mV for 1Cl to -440 mV for 1MeN vs FeCp2/FeCp2+) and νCO of the CO adducts of 1R (ranging from 2093 cm-1 for 1Cl-CO to 2075 cm-1 for 1Me2N-CO) display modest but expected systematic shifts. Dioxygen readily reacts with 1H, 1MeO, and 1Me2N, forming the side-on peroxo-CuII2 complexes [{CuII(R-MePY2)}2(O2)]2+ (2R, also containing some bis-μ-oxo-CuIII2 isomer), but there is no reaction with 1Cl. Stopped-flow studies in dichloromethane show that the formation of 2Me2N from dioxygen and 1Me2N proceeds with a k = 8.2(6) × 104 M-2 s-1 (183 K, ?H- -20.3(6) KJ mol-1,?S=-219(3) J mol -1 K-1 Solutions of 2 R readily oxidize exogenous substrates (9,10- dihydroanthracene → N- methlaniline and formaldehyde, benzyl alcohol→ benzaldehyde, benzhydrol→ benzophenone, and methanol→ formaldehde), forming the bis -μ-hydroxo-Cu II2 complexes [{CuII(R-MePY2)(OH}2]) 2+(3R) Product yields increase as the R- group is made more electron-donating, and in some cases are quantitative with 2Me2N Pseudo-first-order rate constants for THF and methanol the strongest ligand donor (i.e., R=Me 2N). For THF oxidation to THF-OH a nearly 1500-fold increase in reaction rate is observed (kobs=2 (1)×10-5 S-1 for 2H to 3(1)× S-1 for 2Me2N), while methanol oxidation to formaldehyde exhibits an 2000- fold increase ( K obs= 5(1)×10-5 S-1 for 2H to 1(1)×10-1 S-1 for 2Me2N). Copyright
- Zhang, Christiana Xin,Liang, Hong-Chang,Kim, Eun-il,Shearer, Jason,Helton, Matthew E.,Kim, Eunsuk,Kaderli, Susan,Incarvito, Christopher D.,Zuberbuehler, Andreas D.,Rheingold, Arnold L.,Karlin, Kenneth D.
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p. 634 - 635
(2007/10/03)
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- Resonance Raman investigation of equatorial ligand donor effects on the CU2O22+ core in end-on and side-on μ-peroxo-dicopper(II) and bis-μ-oxo-dicopper(III) complexes
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The effect of endogenous donor strength on CU2O2 bonds was studied by electronically perturbing [{(R-TMPA)CuII}2(O2)]2+ and [{(R-MePY2)Cu}2(O2)]2+ (R = H, MeO, Me2N), which form the end-on μ-1,2 bound peroxide and an equilibrium mixture of side-on peroxo- dicopper(II) and bis-μ-oxo-dicopper(III) isomers, respectively. For [{(R-TMPA)CUII}2(O2)]2+, vo-o shifts from 827 to 822 to 812 cm-1 and VCu-O(sym) shifts from 561 to 557 to 551 cm-1, respectively, as R- varies from H to MeO to Me2N. Thus, increasing the N-donor strength to the copper decreases peroxide π*σ donation to the copper, weakening the Cu-O and O-O bonds. A decrease in vCu-O of the bis-μ-oxo- dicopper(III) complex was also observed with increasing N-donor strength for the R-MePY2 ligand system. However, no change was observed for vO-O of the side-on peroxo. This is attributed to a reduced charge donation from the peroxide π*σ orbital with increased N-donor strength, which increases the negative charge on the peroxide and adversely affects the back-bonding from the Cu to the peroxide σ*orbital. However, an increase in the bis-μ-oxo-dicopper(III) isomer relative to side-on peroxo-dicopper(II) species is observed for R-MePY2 with R = H 2N. This effect is attributed to the thermodynamic stabilization of the bis-μ-oxo-dicopper(III) isomer relative to the side-on peroxo-dicopper(II) isomer by strong donor ligands. Thus, the side-on peroxo-dicopper(II)/bis-μ-oxo-dicopper(III) equilibrium can be controlled by electronic as well as steric effects.
- Henson, Mark J.,Vance, Michael A.,Zhang, Christiana Xin,Hong-Chang, Liang,Karlin, Kenneth D.,Solomon, Edward I.
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p. 5186 - 5192
(2007/10/03)
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- Formation of the N-oxides of heteroaromatic nitrogen compounds by perfluorinated oxaziridines
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On treatment with perfluoro-cis-2,3-dialkyloxaziridines, mono-, bi-, and tricyclic nitrogen heteroaromatics afford the corresponding N-oxides under mild reaction conditions and in medium to high yields. The course of the reaction is not altered by the presence of various residues on the ring or in side chains and the N-oxides of polyfunctional, naturally occurring compounds have been prepared.
- Balsarini, Christian,Novo, Barbara,Resnati, Giuseppe
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- Biotransformation of phenyl- and pyridylalkane derivatives in rat liver 9,000xg supernatant (S-9)
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When phenylpropanes were incubated with phenobarbital-pretreated rat liver 9,000xg supernatant (S-9), oxidative hydroxylation occurred to give phenylpropanol (racemic), (1R, 2S)- and (1R, 2R)-phenylpropanediols, (2S)-hydroxyphenylpropanone. Incubation of pyridylethane and propane with S-9 afforded α-pyridylethanol and propanol, but those were optically inactive. During the incubation of 1-phenylpropanone, an asymmetric redox reaction simultaneously occurred to give (2S)-phenylpropanol, (1R, 2S)- or (1R, 2R)-phenylpropanediols and (2R)-hydroxyphenylpropanone. Acetylpyridines were enantioselectively reduced to afford α-pyridylethanols in high optical yields (94-98%ee). The oxidation of pyridylalkane was significantly inhibited by cytochrome P-450 inhibitor (SKF-525A), but reduction of acetylpyridines was not inhibited. Thus, cytochrome P-450 was found to be responsible for the oxidation of pyridylalkane, but not for the reduction of the ketone.
- Takeshita, Mitsuhiro,Miura, Masatomo,Unuma, Yukiko,Iwai, Sakiko,Sato, Izumi,Hongo, Takahiko,Arai, Toshie,Kosaka, Kazuhiro
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p. 831 - 836
(2007/10/03)
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