- Electrochemically Tuned Oxidative [4+2] Annulation and Dioxygenation of Olefins with Hydroxamic Acids
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This work represents the first [4+2] annulation of hydroxamic acids with olefins for the synthesis of benzo[c][1,2]oxazines scaffold via anode-selective electrochemical oxidation. This protocol features mild conditions, is oxidant free, shows high regioselectivity and stereoselectivity, broad substrate scope of both alkenes and hydroxamic acids, and is compatible with terpenes, peptides, and steroids. Significantly, the dioxygenation of olefins employing hydroxamic acid is also successfully achieved by switching the anode material under the same reaction conditions. The study not only reveals a new reactivity of hydroxamic acids and its first application in electrosynthesis but also provides a successful example of anode material-tuned product selectivity.
- Wei, Bang-Yi,Xie, Dong-Tai,Lai, Sheng-Qiang,Jiang, Yu,Fu, Hong,Wei, Dian,Han, Bing
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supporting information
p. 3182 - 3188
(2020/12/11)
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- Tandem selective reduction of nitroarenes catalyzed by palladium nanoclusters
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We report a catalytic tandem reduction of nitroarenes by sodium borohydride (NaBH4) in aqueous solution under ambient conditions, which can selectively produce five categories of nitrogen-containing compounds: anilines, N-aryl hydroxylamines, azoxy-, azo- and hydrazo-compounds. The catalyst is in situ-generated ultrasmall palladium nanoclusters (Pd NCs, diameter of 1.3 ± 0.3 nm) from the reduction of Pd(OAc)2 by NaBH4. These highly active Pd NCs are stabilized by surface-coordinated nitroarenes, which inhibit the further growth and aggregation of Pd NCs. By controlling the concentration of Pd(OAc)2 (0.1-0.5 mol% of nitroarene) and NaBH4, the water/ethanol solvent ratio and the tandem reaction sequence, each of the five categories of N-containing compounds can be obtained with excellent yields (up to 98%) in less than 30 min at room temperature. This tunable catalytic tandem reaction works efficiently with a broad range of nitroarene substrates and offers a green and sustainable method for the rapid and large-scale production of valuable N-containing chemicals.
- Yan, Ziqiang,Xie, Xiaoyu,Song, Qun,Ma, Fulei,Sui, Xinyu,Huo, Ziyu,Ma, Mingming
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supporting information
p. 1301 - 1307
(2020/03/11)
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- A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination
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Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1-disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method.
- Ichikawa, Saki,Zhu, Shaolin,Buchwald, Stephen L.
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supporting information
p. 8714 - 8718
(2018/07/14)
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- Cobalt-Catalyzed Electrophilic Amination of Aryl- and Heteroarylzinc Pivalates with N-Hydroxylamine Benzoates
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Aryl- and heteroarylzinc pivalates can be aminated with O-benzoylhydroxylamines at 25 °C within 2–4 h in the presence of 2.5–5.0 % CoCl2?2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields. This electrophilic amination also provides access to diarylamines and aryl(heteroaryl)amines. A new tuberculosis drug candidate (Q203) was prepared in six steps and 56 % overall yield by using this cobalt-catalyzed amination as the key step.
- Chen, Yi-Hung,Gra?l, Simon,Knochel, Paul
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supporting information
p. 1108 - 1111
(2018/01/01)
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- Visible-Light, Photoredox-Mediated Oxidative Tandem Nitroso-Diels–Alder Reaction of Arylhydroxylamines with Conjugated Dienes
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Arylhydroxylamines were used in the nitroso-Diels–Alder reaction to generate in situ nitrosoarenes under visible-light, catalytic and aerobic conditions. Mixing a solution of aryl- or heteroarylhydroxylamines with conjuguated dienes in the presence of a catalytic amount of Ru(bpy)3Cl2 afforded 3,6-dihydro-1,2-oxazines in good yields under an oxygen atmosphere.
- Santacroce, Veronica,Duboc, Raphael,Malacria, Max,Maestri, Giovanni,Masson, Geraldine
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supporting information
p. 2095 - 2098
(2017/04/24)
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- Hydroxamic Acids as Chemoselective (ortho-Amino)arylation Reagents via Sigmatropic Rearrangement
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The use of readily available hydroxamic acids as reagents for the chemoselective (ortho-amino)arylation of amides is described. This reaction proceeds under metal-free, mild conditions, displays a very broad scope, and constitutes a direct approach for the metal-free attachment of aniline residues to carbonyl derivatives.
- Shaaban, Saad,Tona, Veronica,Peng, Bo,Maulide, Nuno
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supporting information
p. 10938 - 10941
(2017/08/30)
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- Synthesis of N-aryl and N-heteroaryl hydroxylamines via partial reduction of nitroarenes with soluble nanoparticle catalysts
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Polystyrene-supported ruthenium nanoparticles enable the selective hydrazine-mediated reduction of nitroarenes to hydroxylamine products in high yield and selectivity. Key to obtaining the hydroxylamine product in good yield was the use of organic solvents capable of solubilizing the polystyrene-supported nanoparticle catalyst. N-aryl and N-heteroaryl hydroxylamines are generated under exceptionally mild conditions and in the presence of a various easily reduced functional groups.
- Tyler, Jefferson H.,Nazari, S. Hadi,Patterson, Robert H.,Udumula, Venkatareddy,Smith, Stacey J.,Michaelis, David J.
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supporting information
p. 82 - 86
(2016/12/23)
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- TRIFLUOROMETHOXYLATION OF ARENES VIA INTRAMOLECULAR TRIFLUOROMETHOXY GROUP MIGRATION
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The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure: (I), wherein A is an aryl or heteroaryl, each with or without subsutitution; and R1 is -H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), - (alkylaryl), - (alkylheteroaryl), -NH-(alkyl), -N(alkyl)2, -NH-(alkenyl), -NH-(alkynyl) -NH-(aryl), -NH-(heteroaryl), -O-(alkyl), -O-(alkenyl), -O-(alkynyl), -O-(aryl), -O-(heteroaryl), -S-(alkyl), -S- (alkenyl), -S-(alkynyl), -S-(aryl), or -S-(heteroaryl), comprising: (a) reacting a compound having the structure: (II), with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure: (III); and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure: (I).
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Page/Page column 58
(2016/05/02)
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- Probing the Limits of Selectivity in a Recognition-Mediated Reaction Network Embedded within a Dynamic Covalent Library
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Two recognition-mediated reaction processes operating through reactive binary complexes drive resolution of a 24-component dynamic covalent library, assembled from individual aldehydes and nucleophiles. The effectiveness of the library resolution and sele
- Kosikova, Tamara,MacKenzie, Harry,Philp, Douglas
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supporting information
p. 1831 - 1839
(2016/02/20)
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- Influence of the side-group at C=N bridging bond of bis-aryl Schiff bases on the wavelength of absorption maximum of ultraviolet absorption spectra
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The compounds N-(benzylidene)-anilines XArCH=NArY (XBAY), N-(phenyl-ethylene)-anilines XArC(CH3)=NArY (XPEAY) and N-phenyl-α-phenylnitrones XArCH=N(O)ArY (XPNY) have bridging group CH=N, C(CH3)=N and CH=N(O) respectively, in which the C(CH3)=N has a side-group methyl CH3 at carbon end and the CH=N(O) has a side-group O atom at nitrogen end. In this work, a series of XPEAY and XPNY were synthesized, and their longest wavelength maximum λmax (nm) of ultraviolet absorption spectra were measured. Then the change regularity of the νmax (cm-1, νmax=1/λmax) of XPEAY and XPNY were investigated, and they were compared with that of XBAY (reported by ref.26). The results indicate: (1) There are no good linear relationships between the νmax of XBAYs and XPEAYs or XPNYs. (2) In case of a same set of X-Y group couples, the distribution of λmax of XPEAYs is larger than that of XPNYs. (3) The side-group CH3 makes the effect of σ(X) larger than that of σ(Y) on the νmax of XPEAYs, whereas the O atom makes the effect of σ(Y) larger than that of σ(X) on the νmax of XPNYs. (4) The cross-interaction between X and Y has important effect on the all νmax. However, the cross-interaction between CH3 and X/Y has not important effect on the νmax of XPEAY, and the cross-interaction between O and X/Y has not important effect on the νmax of XPNY. Copyright
- Luo, Qingqing,Cao, Chao-Tun,Cao, Zhongzhong,Cao, Chenzhong
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p. 406 - 413
(2016/07/28)
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- An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: Generality, applications and mechanistic investigations
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The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.
- Richmond, Edward,Ling, Kenneth B.,Duguet, Nicolas,Manton, Lois B.,elebi-?lcüm, Nihan,Lam, Yu-Hong,Alsancak, Sezen,Slawin, Alexandra M. Z.,Houk,Smith, Andrew D.
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supporting information
p. 1807 - 1817
(2015/02/19)
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- Rhodium(III)-catalyzed internal oxidative coupling of N-hydroxyanilides with alkenes via C-H activation
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Abstract Described herein is an efficient new method for ortho-olefination of anilides in the presence of AgSbF6 and NaOAc via rhodium(III)-catalyzed internal oxidative C-H bond activation based on hydroxyl as directing and oxidative group. A range of alkenes and functional groups on acetanilides is supported and a possible mechanism is proposed according to the experimental results.
- Wen, Jing,Wu, An,Chen, Pei,Zhu, Jin
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supporting information
p. 5282 - 5286
(2015/08/26)
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- Trifluoromethoxylation of arenes: Synthesis of ortho- Trifluoromethoxylated aniline derivatives by OCF3 migration
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Aryl trifluoromethoxylation by a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxylamine derivatives and intramolecular OCF3 migration is presented. This protocol allows easy access to a wide range of synthetically useful ortho-OCF3 aniline derivatives. In addition, it utilizes bench-stable reagents, is operationally simple, shows high functional-group tolerance, and is amenable to gram-scale as well as one-pot synthesis.Areaction mechanism of a heterolytic cleavage of the N-OCF3 bond followed by recombination of the resulting nitrenium ion and trifluoromethoxide is proposed for the OCF3-migration reaction.
- Hojczyk, Katarzyna N.,Feng, Pengju,Zhan, Chengbo,Ngai, Ming-Yu
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supporting information
p. 14559 - 14563
(2015/01/09)
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- Interrupted fischer-indole intermediates via oxyarylation of alkenyl boronic acids
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The oxyarylation of alkenyl boronic acids with N-arylbenzhydroxamic acids has been achieved under both copper-mediated and copper-catalyzed conditions to provide access to interrupted Fischer-indole intermediates. This transformation is believed to proceed through a copper-promoted C-O bond forming event followed by a [3,3] rearrangement. The scope of the method is described and mechanistic experiments are discussed.
- Wang, Heng-Yen,Anderson, Laura L.
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supporting information
p. 3362 - 3365
(2013/07/26)
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- Total synthesis of ezetimibe, a cholesterol absorption inhibitor
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Ezetimibe (1), a strong β-lactamic cholesterol absorption inhibitor, was synthesized from (R)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one 7. Independent pathways were analyzed in order to select the optimal one, which involved 1,3-dipolar cycloaddition with C-(4-benzyloxyphenyl)-N-(4-fluorophenyl) -nitrone (8), intramolecular nucleophilic displacement at the benzylic position of the lactone, cleavage of the N-O bond, elimination of a water molecule, hydrogenation of the double bond, rearrangement of the six-membered lactone ring into a β-lactam moiety, and final deprotection of the phenolic hydroxyl group. Highly stereoselective Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition was the most crucial step of the synthesis. Owing to the rigid transition state of the cycloaddition, the absolute configuration of the starting lactone controlled the formation of other stereogenic centers of the final molecule 1.
- Sniezek, Marcin,Stecko, Sebastian,Panfil, Irma,Furman, Bartlomiej,Chmielewski, Marek
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p. 7048 - 7057
(2013/08/23)
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- Asymmetric pericyclic cascade approach to spirocyclic oxindoles
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The reaction of chiral N-arylnitrones with carbocyclic alkylarylketenes generates spirocyclic oxindoles in good yields and with excellent levels of enantioselectivity (90-99% ee) via a pericyclic cascade process.
- Richmond, Edward,Duguet, Nicolas,Slawin, Alexandra M. Z.,Lebl, Tomas,Smith, Andrew D.
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supporting information; experimental part
p. 2762 - 2765
(2012/07/14)
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- A formal synthesis of ezetimibe via cycloaddition/rearrangement cascade reaction
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A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of l-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering-Plough group.
- Michalak, Michal,Stodulski, MacIej,Stecko, Sebastian,Mames, Adam,Panfil, Irma,Soluch, Magdalena,Furman, Bartlomiej,Chmielewski, Marek
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experimental part
p. 6931 - 6936
(2011/10/08)
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- A PROCESS FOR THE PREPARATION OF AN ALDEHYDE BETA-LACTAM COMPOUND
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The invention relates to a process for the preparation of an aldehyde beta-lactam compound of formula (I), wherein P1 is H or a protecting group, useful in the preparation of ezetimibe, from a nitrone compound of formula (II). The nitrone compound Il is prepared by reacting 4-fluorophenylhydroxyloamine with OH- protected 4-hydroxybenzaldehyde. The nitrone compound of formula (II) is reacted with an acetylene compound of formula (III) to form a compound of formula (IV), and the compound of formula (IV), after optional deprotection, is oxidized to obtain an aldehyde of formula (V), which undergoes isomerisation to the compound of formula (I). The subject of the invention are also novel compounds of formulas (II) and (IV).
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Page/Page column 23
(2010/09/17)
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- METHOD FOR PRODUCING ARYLHYDROXYLAMINE
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PROBLEM To provide a method for producing an arylhydroxylamine compound efficiently and safely under mild conditions. MEANS FOR SOLVING THE PROBLEM The present invention relates to a method for producing an arylhydroxylamine compound, which comprises contacting a nitroaryl compound with a hydrogen source in the coexistence of a platinum catalyst supported on amino group-coordinated silica and a poisoning agent.
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Page/Page column 23-24
(2010/03/04)
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- Selective synthesis of N-aryl hydroxylamines by the hydrogenation of nitroaromatics using supported platinum catalysts
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Various substituted nitroaromatics were successfully hydrogenated to the corresponding N-aryl hydroxylamines in excellent yields (up to 99%) using supported platinum catalysts such as Pt/SiO2 under a hydrogen atmosphere (1 bar) at room temperature. The key to the fast and highly selective formation of hydroxylamines is the addition of small amounts of amines such as triethylamine and dimethyl sulfoxide; amines promote the conversion of nitroaromatics, while dimethyl sulfoxide inhibits further hydrogenation of hydroxylamines to anilines. The promotive effect depends on which type of amine and primary amine was most effective. The hydrogenation efficiently proceeded in common organic solvents, including isopropanol, diethyl ether, and acetone. This methodology should extend the application range of conventional solid catalysts to fine chemicals synthesis. The Royal Society of Chemistry 2009.
- Takenaka, Yasumasa,Kiyosu, Takahiro,Choi, Jun-Chul,Sakakura, Toshiyasu,Yasuda, Hiroyuki
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supporting information; experimental part
p. 1385 - 1390
(2010/05/18)
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- para-Substituted N-Nitroso-N-oxybenzenamine ammonium salts: A new class of redox-sensitive nitric oxide releasing compounds
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N-Nitroso-N-oxybenzenamine ammonium salts with -OMe, -Me, -H, -F, -Cl, - CF3, and -SO2Me substituents at the para position of the phenyl ring constitute a new class of-redox sensitive nitric oxide (NO) releasing compounds. These compounds yield nitric oxide and the corresponding nitrosobenzene derivatives by a spontaneous dissociation mechanism after undergoing a one electron oxidation. Oxidation of these compounds can be achieved through chemical, electrochemical and enzymatic methods. It was observed electrochemically that the amount of NO generated was dependent on the substituent effect and the applied oxidation potential. Electron- withdrawing substituents increase the oxidation potential of the compound. A linear correlation was observed when the peak potentials for the oxidation were graphed versus the Hammett substituent constant. Density functional theory calculations were also performed on this series of compounds. The theoretical oxidation energies of the corresponding anions show a strong linear correlation with the experimental potentials. Furthermore, enzymatic oxidation using horseradish peroxidase showed a similar substituent effect. These results indicate that substitution at the para position of the phenyl ring has a profound effect on the stability, oxidation potential and enzymatic kinetic properties of the compounds. Thus para-substituted N- nitroso-N-oxybenzenamine salts comprise a new class of redox-sensitive nitric oxide releasing agents. (C) 2000 Elsevier Science Ltd.
- McGill, Andrea D.,Zhang, Wei,Wittbrodt, Joanne,Wang, Jianqiang,Schlegel, H. Bernhard,Wang, Peng George
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p. 405 - 412
(2007/10/03)
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