- Synthesis of the cis diastereoisomer of 5-diethoxyphosphoryl-5-methyl-3- phenyl-1-pyrroline N-oxide (DEPMPPOc) and ESR study of its superoxide spin adduct
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The cis and trans diastereoisomers of 5-diethoxyphosphoryl-5-methyl-3- phenyl-1-pyrroline N-oxide (DEPMPPO), the C(3)-phenyl analogue of DEPMPO, were prepared in three steps from phenylacetaldehyde and used in ESR-spin trapping of various carbon-, oxygen- and sulfur-centred radicals. In the case of the cis-isomer, the presence of the phenyl group cancels the alternating line width phenomenon observed for the DEPMPO-OOR (R = H, But) spin adducts. The ESR spectra of the DEPMPPOc-OOR spin adducts exhibit more straightforward patterns and are more easily assignable.
- Nsanzumuhire, Céline,Clément, Jean-Louis,Ouari, Olivier,Karoui, Hakim,Finet, Jean-Pierre,Tordo, Paul
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Read Online
- Role of glutathione S-transferases A1-1, M1-1, and P1-1 in the detoxification of 2-phenylpropenal, a reactive felbamate metabolite
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Felbamate has proven to be an effective therapy for treating refractory epilepsy. However, felbamate therapy has been limited due to the associated reports of hepatotoxicity and aplastic anemia. Previous research from our laboratory has proposed 2-phenylpropenal as the reactive metabolite in felbamate bioactivation and identified its mercapturates in the urine of rats and patients undergoing felbamate therapy. While the reaction between 2-phenylpropenal and GSH has been shown to occur spontaneously under physiological conditions, the potential catalysis by glutathione transferases (GST) has remained unknown. The work presented here demonstrates a role for GST in the detoxification of 2-phenylpropenal. The kinetic data show that 2-phenylpropenal is a substrate for all three isoforms tested, with a kcat/Km of 0.275 ± 0.035 μM-1 s-1 for GSTM1-1, 0.164 ± 0.005 μM-1 s-1 for GSTP1-1, and 0.042 ± 0.005 μM-1 s-1 for GSTA1-1. Given that electrophilic substrates such as 2-propenal have been shown to inhibit GSTs, we also examined the inhibition of GSTM1-1, GSTP1-1 and GSTA1-1 by 2-phenylpropenal. The enzyme inhibition studies demonstrate that 2-phenylpropenal inhibits GSTP1-1 and GSTM1-1. The inhibition of GSTP1-1 was completely reversible upon filtration and reconstitution in buffer containing 10 mM GSH. However, 2-phenylpropenal inhibition of GSTM1-1 was irreversible under the same conditions. The irreversible inhibition of GSTM1-1 may be important in understanding the toxicities associated with felbamate. Given that 2-phenylpropenal is both a substrate and irreversible inhibitor for GSTM1-1, GSTM1-1 represents a potential target for 2-phenylpropenal haptenization in vivo, which may in turn mediate the observed idiosyncratic reactions.
- Dieckhaus, Christine M.,Roller, Shane G.,Santos, Webster L.,Sofia, R. Duane,Macdonald, Timothy L.
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Read Online
- Rhodium-Catalyzed Regio- And Enantioselective Allylic Amination of Racemic 1,2-Disubstituted Allylic Phosphates
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Alkynylphosphines are rarely used as ligands in asymmetric metal catalysis. We synthesized a series of chiral bis(oxazoline)alkynylphosphine ligands and used them in Rh-catalyzed highly regio- and enantioselective allylic amination reactions of 1,2-disubstituted allylic phosphates. Chiral 1,2-disubstituted allylic amines were synthesized in up to 95% yield with >20:1 branched/linear (b/l) ratio and 99% ee from racemic 1,2-disubstituted allylic precursors. The sterically smaller linear alkynyl group on the P atom in the bis(oxazoline)alkynylphosphine ligands was the key to fit the new requirements of the introduction of bulky 2-R′ groups.
- Li, Changkun,Shu, Mouhai,Sun, Minghe,Xu, Wen-Bin
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supporting information
p. 8255 - 8260
(2021/06/27)
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- Two C=C Bond Participation in Annulation to Pyridines Based on DMF as the Nonadjacent N and C Atom Donors
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Two C=C bond participation in annulation to pyridines using N,N-dimethylformamide (DMF) as the N1 and C4 synthons has been carried out. In this reaction, DMF contributed one N atom and one C atom to two disconnected positions of pyridine ring, with no need for an additional nitrogen source. Two C=C bonds in two molecules of substituted styrenes offered four carbon atoms in the presence of iodine and persulfate. With the optimized conditions in hand, both symmetric and unsymmetric diaryl-substituted pyridines were obtained in useful yields. On the basis of relevant literature and a series of control experimental results, a possible mechanism was proposed in this work, which may demonstrate how DMF provides both N1 and C4 sources.
- Su, Miao-Dong,Liu, Hai-Ping,Cao, Zhong-Zhong,Liu, Yufeng,Li, Hui,Nie, Zhi-Wen,Yang, Tong-Lin,Luo, Wei-Ping,Liu, Qiang,Guo, Can-Cheng
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p. 13446 - 13453
(2021/10/12)
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- Selective Rhodium-Catalyzed Hydroformylation of Terminal Arylalkynes and Conjugated Enynes to (Poly)enals Enabled by a π-Acceptor Biphosphoramidite Ligand
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The hydroformylation of terminal arylalkynes and enynes offers a straightforward synthetic route to the valuable (poly)enals. However, the hydroformylation of terminal alkynes has remained a long-standing challenge. Herein, an efficient and selective Rh-catalyzed hydroformylation of terminal arylalkynes and conjugated enynes has been achieved by using a new stable biphosphoramidite ligand with strong π-acceptor capacity, which affords various important E-(poly)enals in good yields with excellent chemo- and regioselectivity at low temperatures and low syngas pressures.
- Zhao, Jiangui,Zheng, Xueli,Tao, Shaokun,Zhu, Yuxin,Yi, Jiwei,Tang, Songbai,Li, Ruixiang,Chen, Hua,Fu, Haiyan,Yuan, Maolin
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supporting information
p. 6067 - 6072
(2021/08/16)
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- Method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and diphosphine ligand used in method
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The invention discloses a method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and a diphosphine ligand used in the method. According to the invention, indole-substituted phosphoramidite diphosphine ligand which is stable in air and insensitive to light is synthesized by utilizing a continuous one-pot method, and the indole-substituted phosphoramidite diphosphine ligand and a rhodium catalyst are used for jointly catalyzing to successfully achieve a hydroformylation reaction of aromatic terminal alkyne and terminal conjugated eneyne under the condition of synthesis gas for the first time, so that an olefine aldehyde structure compound can be rapidly and massively prepared, and particularly, a polyolefine aldehyde structure compound which is more difficult to synthesize in the prior art can be easily prepared and synthesized, and a novel method is provided for synthesis and modification of drug molecules, intermediates and chemical products.
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Paragraph 0126-0131
(2021/05/29)
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- Saegusa Oxidation of Enol Ethers at Extremely Low Pd-Catalyst Loadings under Ligand-free and Aqueous Conditions: Insight into the Pd(II)/Cu(II)-Catalyst System
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A highly efficient and practical Pd(II)/Cu(OAc)2-catalyst system of Saegusa oxidation, which converts enol ethers to the corresponding enals with a number of diverse substrates at extremely low catalyst loadings (500 mol ppm) under ligand-free and aqueous conditions, is described. Its synthetic utility was demonstrated by large-scale applications of the catalyst system to important nature molecules. This work allows Saegusa oxidation to become a highly practical approach to preparing enals and also suggests new insight into the Pd(II)/Cu(II)-catalyst system for dehydrogenation of carbonyl compounds and decreasing Pd-catalyst loadings.
- Zhu, Quan,Luo, Yunsong,Guo, Yongyan,Zhang, Yushun,Tao, Yunhai
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p. 5463 - 5476
(2021/05/05)
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- Method for preparing olefine aldehyde through catalytic oxidation of enol ether
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The invention relates to the technical field of olefine aldehyde preparation, and provides a method for preparing olefine aldehyde through catalytic oxidation of enol ether. According to the invention, a palladium catalyst, a copper salt, a solvent and enol ether are mixed and subjected to a catalytic oxidation reaction to obtain olefine aldehyde. According to the method, the copper salt is used as the oxidizing agent, the mixed solvent of water and acetonitrile is used as the reaction solvent, and the volume ratio of water to acetonitrile in the mixed solvent is controlled to be (3-7): (3-7), so that the catalytic oxidation reaction can be smoothly carried out in the mixed solvent with a specific ratio, and the generation of palladium black precipitate can be avoided. The method provided by the invention has the advantages of simple steps, low reagent cost, no need of dangerous reagents, wide substrate adaptability and small catalyst dosage. Furthermore, octadecane mercaptan is added to promote the catalytic oxidation reaction, and when the dosage of the palladium catalyst is extremely low, the olefine aldehyde yield can be greatly increased by adding octadecane mercaptan.
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Paragraph 0082-0086; 0088
(2021/06/23)
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- Formal Enone α-Arylation via I(III)-Mediated Aryl Migration/Elimination
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A formal enone α-arylation is described. This metal-free transformation relies on the I(III)-mediated skeletal reorganization of silyl enol ethers and features mild conditions, good yields, and high stereoselectivities for β-substituted enones.
- Martins, Bruna S.,Kaiser, Daniel,Bauer, Adriano,Tiefenbrunner, Irmgard,Maulide, Nuno
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supporting information
p. 2094 - 2098
(2021/04/05)
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- Modular Synthesis of α-Substituted Alkenyl Acetals by a Palladium-Catalyzed Suzuki Reaction of α-Haloalkenyl Acetals with Organoboranes
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A modular and straightforward synthetic strategy for the preparation of α-substituted alkenyl acetals has been developed. α-Haloalkenyl acetals react smoothly with (het)aryl boronic acids, aryl boronates, or B-Alkyl-9-borabicyclo[3.3.1]nonanes through Pd-catalyzed Suzuki cross-coupling under mild conditions with good to high yields. This protocol features a broad substrate scope and good functional-group compatibility, and is easily scaled up.
- Zhang, Li
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supporting information
p. 723 - 727
(2021/02/26)
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- Nickel-Catalyzed Asymmetric Reductive 1,2-Carboamination of Unactivated Alkenes
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Starting from diverse alkene-tethered aryl iodides and O-benzoyl-hydroxylamines, the enantioselective reductive cross-electrophilic 1,2-carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β-chiral amines with an enantioenriched aryl-substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.
- He, Jun,Xue, Yuhang,Han, Bo,Zhang, Chunzhu,Wang, You,Zhu, Shaolin
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supporting information
p. 2328 - 2332
(2020/01/08)
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- Bromomethyl Silicate: A Robust Methylene Transfer Reagent for Radical-Polar Crossover Cyclopropanation of Alkenes
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A general protocol for visible-light-induced cyclopropanation of alkenes was developed with bromomethyl silicate as a methylene transfer reagent, offering a robust tool for accessing highly valuable cyclopropanes. In addition to α-aryl or methyl-substituted Michael acceptors and styrene derivatives, the unactivated 1,1-dialkyl ethylenes were also shown to be viable substrates. Apart from realizing the cyclopropanation of terminal alkenes, the methyl transfer reaction has been further demonstrated to be amenable to the internal olefins. The photocatalytic cyclopropanation of 1,3-bis(1-arylethenyl)benzenes was also achieved, giving polycyclopropane derivatives in excellent yields. With late-stage cyclopropanation as the key strategy, the synthetic utility of this transformation was also demonstrated by the total synthesis of LG100268.
- Luo, Wenping,Fang, Yewen,Zhang, Li,Xu, Tianhang,Liu, Yongjun,Li, Yan,Jin, Xiaoping,Bao, Jiakan,Wu, Xiaodong,Zhang, Zongyong
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supporting information
p. 1778 - 1781
(2020/03/11)
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- C -Methylation of Alcohols, Ketones, and Indoles with Methanol Using Heterogeneous Platinum Catalysts
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A versatile, selective, and recyclable heterogeneous catalytic method for the methylation of C-H bonds in alcohols, ketones, and indoles with methanol under oxidant-free conditions using a Pt-loaded carbon (Pt/C) catalyst in the presence of NaOH is reported. This catalytic system is effective for various methylation reactions: (1) the β-methylation of primary alcohols, including aryl, aliphatic, and heterocyclic alcohols, (2) the α-methylation of ketones, and (3) the selective C3-methylation of indoles. The reactions are driven by a borrowing-hydrogen mechanism. The reaction begins with the dehydrogenation of the alcohol(s) to afford aldehydes, which subsequently undergo a condensation reaction with the nucleophile (aldehyde, ketone, or indole), followed by hydrogenation of the condensation product by Pt-H species to yield the desired product. In all of the methylation reactions explored in this study, the Pt/C catalyst exhibits a significantly higher turnover number than other previously reported homogeneous catalytic systems. Moreover, it is demonstrated that the high catalytic activity of Pt can be rationalized in terms of the adsorption energy of hydrogen on the metal surface, as revealed by density functional theory calculations on different metal surfaces.
- Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Jamil, Md. A. R.,Toyao, Takashi,Shimizu, Ken-Ichi
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p. 3091 - 3103
(2018/04/14)
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- Oxidative [3+3] Annulation of Atropaldehyde Acetals with 1,3-Bisnucleophiles: An Efficient Method of Constructing Six-Membered Aromatic Rings, Including Salicylates and Carbazoles
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An oxidative [3+3] annulation of atropaldehyde acetals with various 1,3-bisnucleophiles was developed using either N-bromosuccinimide or copper(II) bromide as oxidizing reagent and Br?nsted or Lewis acids as catalyst. The [3+3] annulations can be considered mechanistically as oxidizing reagent-induced acid-acid-catalyzed domino reactions established through the concept of auto-tandem catalysis. Alkyl acetoacetates, α-(indol-2-yl)acetate, anilines, 1-methyl-1H-pyrazol-3-amine, ethyl 5-amino-1H-pyrazole-3-carboxylate, and 3-amino-1H-indazole can all be used as 1,3-bisnucleophiles in this type of transformation. The established reactions can very efficiently construct six-membered aromatic rings, including salicylates and carbazoles. A four-step method of synthesizing the anti-inflammatory agent diflunisal was also developed based on the oxidative [3+3] annulation reaction, and the yield was high. (Figure presented.).
- Gu, Yanlong,Wu, Fengtian,Yang, Jian
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p. 2727 - 2741
(2018/07/29)
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- Rhodium-catalyzed synthesis of 1,2-dihydropyridine by a tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole
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A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including formation of α-imino rhodium carbene, 1,2-migration of an acetoxy group and six electron electrocyclic ring closure was reported. The migration of the OAc group with excellent chemoselectivity was the crucial process, leading to the formation of 1,2-dihydropyridine specifically in up to 90% yield. Several transformations of the dihydropyridine product were also achieved illustrating the potential of the protocol in organic synthesis. Based on the observation of the intermediate, a plausible mechanism was proposed.
- Dai, Haican,Yu, Sisi,Cheng, Wanli,Xu, Ze-Feng,Li, Chuan-Ying
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supporting information
p. 6417 - 6420
(2017/07/10)
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- Catalytic Asymmetric Cycloadditions of Silyl Nitronates Bearing α-Aryl Group
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1,3-Dipolar cycloadditions of 2-alkylacroleins or atropaldehyde with triisopropylsilyl nitronates bearing an α-aryl group produced 3-aryl-2-isoxazolines having a chiral quaternary center in up to 94% ee and up to 88% yield with the aid of Corey’s oxazaborolidine catalyst. Specifically, the TIPS nitronate with an α-(p-methoxyphenyl) group gave mainly the 2-isoxazolines having an all-carbon quaternary center.
- Jiang, Minghui,Feng, Lifei,Feng, Juanjuan,Jiao, Peng
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p. 2210 - 2213
(2017/05/12)
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- Peroxotantalate-Based Ionic Liquid Catalyzed Epoxidation of Allylic Alcohols with Hydrogen Peroxide
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The efficient and environmentally benign epoxidation of allylic alcohols has been attained by using new kinds of monomeric peroxotantalate anion-functionalized ionic liquids (ILs=[P4,4,4,n]3[Ta(O)3(η-O2)], P4,4,4,n=quaternary phosphonium cation, n=4, 8, and 14), which have been developed and their structures determined accordingly. This work revealed the parent anions of the ILs underwent structural transformation in the presence of H2O2. The formed active species exhibited excellent catalytic activity, with a turnover frequency for [P4,4,4,4]3[Ta(O)3(η-O2)] of up to 285 h?1, and satisfactory recyclability in the epoxidation of various allylic alcohols under very mild conditions by using only one equivalent of hydrogen peroxide as an oxidant. NMR studies showed the reaction was facilitated through a hydrogen-bonding mechanism, in which the peroxo group (O–O) of the peroxotantalate anion served as the hydrogen-bond acceptor and hydroxyl group in the allylic alcohols served as the hydrogen-bond donor. This work demonstrates that simple monomeric peroxotantalates can catalyze epoxidation of allylic alcohols efficiently.
- Ma, Wenbao,Chen, Chen,Kong, Kang,Dong, Qifeng,Li, Kun,Yuan, Mingming,Li, Difan,Hou, Zhenshan
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p. 7287 - 7296
(2017/05/31)
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- Tandem Diels-Alder and retro-ene reactions of 1-sulfenyl- and 1-sulfonyl-1,3-dienes as a traceless route to cyclohexenes
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A pericyclic approach for the synthesis of six-membered ring structures is described. The method employs 1,3-dienes with a 1-sulfur substituent in a tandem sequence of Diels-Alder and retro-ene reactions. In this pairing of [4 + 2] cycloaddition and 1,5-sigmatropic rearrangement, 1-sulfenyl-1,3-dienes engage in Diels-Alder reactions with electron-deficient dienophiles. Subsequently, the sulfenyl group of the cycloadducts is oxidized and unmasked to form allylic sulfinic acids, which undergo sterospecific reductive transposition via sulfur dioxide extrusion. The sequence can also include an inverse electron demand Diels-Alder reaction by using a 1-sulfonyl-1,3-diene. This combination of two pericyclic events offers novel stereocontrolled access to cyclohexenes that are inaccessible via a direct [4 + 2] cycloaddition route.
- Choi, Jin,Park, Hoyoon,Yoo, Hyun Jung,Kim, Sinae,Sorensen, Erik J.,Lee, Chulbom
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supporting information
p. 9918 - 9921
(2014/08/05)
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- Selective palladium-catalyzed hydroformylation of alkynes to α,β-Unsaturated Aldehydes
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Atom-efficient: A selective palladium catalyst system is used for the hydroformylation of alkynes (see picture). In this syngas reaction, various alkynes were smoothly transformed to synthetically interesting α,β-unsaturated aldehydes in good yields with high regio- and stereoselectivity. Copyright
- Fang, Xianjie,Zhang, Min,Jackstell, Ralf,Beller, Matthias
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p. 4645 - 4649
(2013/05/22)
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- Syntheses of mono-, di-, and trifluorinated styrenic monomers
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Concise syntheses of gram quantities of three fluorinated -methylstyrenic monomers suitable for polymerisation studies are disclosed, all based on the use of reasonably priced commercially available starting materials and reagents. Georg Thieme Verlag Stuttgart New York.
- Walkowiak, Justyna,Del Campo, Teresa Martinez,Ameduri, Bruno,Gouverneur, Veronique
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experimental part
p. 1883 - 1890
(2010/08/20)
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- Palladium-nanoparticle-catalysed ullmann reactions in ionic liquids with aldehydes as the reductants: Scope and mechanism
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An efficient Ullmann-type reductive homocoupling of aryl, vinyl and heteroaryl halides can be promoted by an aldehyde in tetraalkylammonium ionic liquids under very mild reaction conditions. This simple procedure generates symmetrical biaryls under relatively mild conditions. The ionic liquid is crucial for this process because it behaves simultaneously as a base, ligand and reaction medium. The role of the aldehyde is also discussed and a general mechanism for this unusual reaction is proposed. These results open the way to a new efficient method of Pd-catalysed dehydrogenation of carbonyl compounds.
- Calo, Vincenzo,Nacci, Angelo,Monopoli, Antonio,Cotugno, Pietro
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experimental part
p. 1272 - 1279
(2009/08/14)
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- SULFONYLPYRAZOLE AND SULFONYLPYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS
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This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.
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Page/Page column 29
(2008/06/13)
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- Highly regioselective terminal alkynes hydroformylation and Pauson-Khand reaction catalysed by mesoporous organised zirconium oxide based powders
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Zirconia-silica mesoporous powders act as very efficient heterogeneous catalysts for both alkyne hydroformylation and Pauson-Khand reaction and yield regioselectivities opposite to those usually observed. The Royal Society of Chemistry 2006.
- Goettmann, Frederic,Le Floch, Pascal,Sanchez, Clement
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p. 180 - 182
(2008/02/08)
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- Gold(I)-catalyzed oxidative cleavage of a C-C double bond in water
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Oxidative cleavage of the C=C bond to afford ketone or aldehyde products with tert-butyl hydrogenperoxide (TBHP) as the oxidant can be catalyzed by AuCl with neocuproine (1) in water.
- Xing, Dong,Guan, Bingtao,Cai, Guixin,Fang, Zhao,Yang, Liping,Shi, Zhangjie
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p. 693 - 696
(2007/10/03)
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- AMINE-BASED AND AMIDE-BASED INHIBITORS OF SEMICARBAZIDE-SENSITIVE AMINE OXIDASE (SSAO) ENZYME ACTIVITY AND VAP-1 MEDIATED ADHESION USEFUL FOR TREATMENT OF DISEASES
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Compositions and methods are disclosed for inhibiting semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1). The compounds disclosed are amine-containing and amide-containing compounds. The compounds and compositions are useful for treatment of diseases, including inflammation, inflammatory diseases and autoimmune disorders.
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Page/Page column 85
(2010/02/13)
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- Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement as an equivalent of the inverse electron demand hetero Diels-Alder reaction
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A highly stereoselective formal inverse electron demand hetero Diels-Alder reaction (HDA) occurs on reaction of 2-aryl-α,β-unsaturated aldehydes with cyclopentadiene. The major pathway for this transformation is shown to be a Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement.
- Davies, Huw M. L.,Dai, Xing
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p. 6680 - 6684
(2007/10/03)
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- The chemistry, toxicology, and identification in rat and human urine of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one: A reactive metabolite in felbamate bioactivation
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4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one has been proposed to be a reactive metabolite of the anti-epileptic drug felbamate [Thompson et al. (1996) Chem. Res. Toxicol. 9, 1225-1229]. 4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one exists in equilibrium with 3-oxo-2-phenylpropyl aminooate, which is known to eliminate to generate 2-phenylpropenal. Thus, this species is postulated to be a latent form of the ultimate reactive metabolite, 2-phenylpropenal. The chemistry of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is proposed to parallel that of 4-hydroxycyclophosphamide, the bioactivated form of cyclophosphamide that undergoes ring-opening to aldophosphamide and subsequent elimination to afford 2-propenal (acrolein). The work presented here reports the chemical synthesis of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one and demonstrates that under buffered conditions it exists in equilibrium with 3-oxo-2-phenylpropyl aminooate. The rate-limiting step in the decomposition of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is the irreversible β-elimination from 3-oxo-2-phenylpropyl aminooate to 2-phenylpropenal. We have found the half-life of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one to be 4.6 ± 0.4 h under in vitro conditions that mimic the physiological setting. As a consequence of the relatively long half-life of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one, we have sought evidence for the significance of this pathway in experimental and clinical conditions. We report here the observation of this metabolite in the urine of rats being treated with 3-hydroxy-2-phenylpropyl aminooate, the esterase-mediated metabolite of felbamate, and in the urine of patients undergoing felbamate therapy. In addition, we have shown that 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is toxic to cultured ceils in a time-dependent manner, most likely as a result of its decomposition to 2-phenylpropenal. Taken together, the data support the hypothesis that 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one represents a "time-release" form of 2-phenylpropenal capable of traveling to distal sites from its locus of bioactivation and thereby mediates felbamate associated toxicities.
- Dieckhaus,Santos,Sofia,Macdonald
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p. 958 - 964
(2007/10/03)
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- Preparation of 2-alkyl- and 2-acylpropenals from 5-(trifluoromethanesulfonyloxy)-4H-1,3-dioxin: A versatile acrolein α-cation synthon
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5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin (3) participates in a variety of nucleophilic substitution reactions with cuprate reagents or in palladium catalyzed cross-coupling reactions to provide 5-substituted-4H-1,3-dioxins 5. Upon thermolysis, these compounds undergo facile retrocycloaddition reactions to generate the corresponding 2-substituted acroleins which, if necessary, can be trapped in situ with dienes or heterodienophiles. In particular, the heretofore unknown 2-acylacroleins can be generated using this methodology and trapped with enol ethers to afford 5-acyl-3,4-dihydro-2H-pyrans (6g,h), a substructural unit common to many natural products. (C) 2000 Elsevier Science Ltd.
- Fearnley, Stephen P.,Funk, Raymond L.,Gregg, Robert J.
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p. 10275 - 10281
(2007/10/03)
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- Molecule-Induced Homolysis versus "Concerted Oxenoid Oxygen Insertion" in the Oxidation of Organic Compounds by Dimethyldioxirane
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Evidence for a molecule-induced homolysis of dimethyldioxirane by several classes of organic compounds (alkanes, alkenes, ethers, alcohols, aldehydes, iododerivatives) is reported. Carbon-centered radicals, arising from alkanes, ethers, and aldehydes, are trapped by CBrCl3 or protonated quinolines. The dramatic influence of oxygen in these reactions, as well as the formation of products of induced homolysis of the dioxirane by carbon-centered radicals (CH4, CH3OH, CH3COOCH3, ROCOCH3, CH3COOCH2COCH3), strongly supports a radical mechanism. With alkenes and iodo derivatives the induced homolysis would lead to diradical intermediates, whose very fast fragmentation would prevent detection, but circumstantial evidence supports a radical mechanism.
- Bravo, Anna,Fontana, Francesca,Fronza, Giovanni,Minisci, Francesco,Zhao, Lihua
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p. 254 - 263
(2007/10/03)
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- Metal-Catalyzed Oxidations with Pinane Hydroperoxide: A Mechanistic Probe to Distinguish between Oxometal and Peroxometal Pathways
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The relative reactivities of tert-butyl hydroperoxide (TBHP) and pinane hydroperoxide (PHP) in metal (Cr, Mo, Ru, Se, V, and Zr)-catalyzed oxidations were compared. When these oxidations involve rate-limiting oxygen transfer from a peroxometal species to the substrate huge differences between TBHP and PHP were observed, e.g., molybdenum-catalyzed epoxidation of cyclohexene with TBHP gave a 98% yield while PHP gave 0%. When the reaction involves reaction of an oxometal species with the substrate as the rate-limiting step, little or no difference is observed, e.g., the selenium-catalyzed allylic oxidation of β-pinene gave a 96% and 99% yield with TBHP and PHP, respectively. Small but significant differences are observed when reoxidation of the catalyst by the hydroperoxide to the active oxometal species is the rate-limiting step; e.g., the chromium-catalyzed oxidation of carveol gave carvone in 89% and 24% yield with TBHP and PHP, respectively. Hence, the effect of RO2H structure on rate is dependent on the rate-limiting step.
- Lempers,Ripolles i Garcia,Sheldon
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p. 1408 - 1413
(2007/10/03)
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- Triplet-sensitized photorearrangement of 2-phenylallyl phosphites
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The triplet-sensitized photorearrangements of 2-phenylallyl phosphites 1, 3, and 4 to the corresponding 2-phenylallylphosphonates 1a, 3a, and 4a are shown to proceed with complete regioselectivity (5 → 6 and Scheme 1). A mechanism is proposed in which the
- Bentrude, Wesley G.,Dockery, Kevin P.,Ganapathy, Srinivasan,Lee, Sueg-Geun,Tabet, Michael,Wu, Yuh-Wern,Cambron, R. Thomas,Harris, Joel M.
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p. 6192 - 6201
(2007/10/03)
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- Contrast media synthesized from polyaldehydes
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Microparticles comprising biodegradable polymers, characterized in that they are synthesized from polymerizable aldehydes, which optionally contain additives and/or crosslinkers capable of copolymerization, optionally surfactants or surfactant mixtures, gases and/or highly volatile liquids in free or bound form, coupling agents, optionally biomolecules or macromolecules bound by these coupling agents as well as optionally diagnostically or therapeutically effective components, are suitable as ultrasonic contrast media.
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- Synthesis and in vitro reactivity of 3-carbamoyl-2- phenylpropionaldehyde and 2-phenylpropenal: Putative reactive metabolites of felbamate
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We propose that 3-carbamoyl-2-phenylpropionaldehyde is an intermediate in the metabolism of felbamate, an anti-epileptic drug with a unique profile of therapeutic activity, and undergoes a cascade of chemical reactions responsible for the toxic properties of the parent drug. To test this hypothesis, we have synthesized 3-carbamoyl-2-phenylpropionaldehyde and evaluated its in vitro reactivity. This molecule was found to be highly unstable at physiological pH (t(1/2) ≤ 30 s) and to undergo facile elimination to 2-phenylpropenal, an α, β-unsaturated aldehyde commonly termed atropaldehyde. However, the predominant reaction pathway for 3- carbamoyl-2-phenylpropionaldehyde was reversible cyclization to generate 4- hydroxy-5-phenyltetrahydro-1,3-oxazin-2-one, a urethane that has a considerably longer half-life at physiological pH (t(1/2) ≤ 5 h) and may serve as a stable reservoir of the reactive aldehyde both in vitro and in vivo. Atropaldehyde is a potent electrophile and was found to exhibit cytotoxicity to cultured fibroblasts (50% growth inhibition (GI50) = 4.1 ± 1.1 μM) comparable to the known unsaturated aldehyde toxins, 4-hydroxy-2- nonenal and acrolein. 3-Carbamoyl-2-phenylpropionaldehyde also exhibited significant cytotoxicity (GI50 = 53 ± 8 μM), whereas 2-phenyl-1, 3- propanediol monocarbamate (GI50 > 500 μM) and 3-carbamoyl-2- phenylpropionic acid (GI50 > 500 μM) were nontoxic. We have additionally demonstrated the formation of a glutathione-atropaldehyde conjugate from the in vitro incubation of 3-carbamoyl-2-phenylpropionaldehyde with glutathione. Thus, the potent cytotoxicity and potential allergenicity of atropaldehyde implicate this unsaturated aldehyde as a possible causative agent in the toxicities observed with felbamate treatment.
- Thompson, Charles D.,Kinter, Michael T.,Macdonald, Timothy L.
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p. 1225 - 1229
(2007/10/03)
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- Oxidation of alkyl and aryl iodides, phenylacetaldehyde and alkenes by dimethyldioxirane. Reaction products and mechanism
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Alkyl and aryl iodides are smoothly oxidized to iodosoderivatives and phenylacetaldehyde is oxidized to phenylacetic acid or benzyl acetate by dimethyldioxirane depending on the presence or not of oxygen. These results and the epoxidation or the allylic oxidation of alkenes by the same reagent are explained by a general free-radical mechanism.
- Bravo, Anna,Fontana, Francesca,Fronza, Giovanni,Minisci, Francesco,Serri, Anna
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p. 6945 - 6948
(2007/10/02)
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- Novel allylic oxidation reagents
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Pentafluorobenzeneseleninic acid and 2-(N-oxido)pyridineseleninic anhydride were prepared and used efficiently in the oxidation of alcohols and in the allylic oxidation of alkenes.
- Barton, Derek H. R.,Wang, Tie-Lin
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p. 5149 - 5152
(2007/10/02)
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- Hypervalent iodine oxidation of allenes: Synthesis of 3-acetoxy-3-alkoxypropynes, 2-alkoxy-3-tosyloxypropanals and phenyl-substituted propenals and propenones
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1-Alkoxyallenes yield 3-acetoxy-3-alkoxypropynes upon oxidation with [(diacetoxy)iodo]benzene at -78°C in dichloromethane. Treatment with [hydroxy(tosyloxy)iodo]benzene under similar conditions gives 2-alkoxy-3-tosyloxypropanals. Phenyl-substituted propen
- Moriarty,Hopkins,Vaid,Vaid,Levy
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p. 847 - 849
(2007/10/02)
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- The Influence of Intramolecular Dynamics on Branching Ratios in Thermal Rearrangements
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1- and 2-phenylbicyclohex-2-enes-5-d undergo thermal rearrangement to give products, differing only in the location of the deuterium, in ratio of about 9:1, but with identical activation enthalphies.Similarly, opticallly active trans-2-methyl-1-(trans-2-phenylethenyl)cyclopropane is found to rearrange to enantiomeric methylphenylcyclopentenes that are formed in a 5.9:1 ratio but with virtually identicyl activation enthalphies.Barring repeated coincidence, these results do not seem to be explicable within the framework of statistical theories of unimolecular kinetics such as RRKM theory, transition state theory, and variational transition state theory.The possible influence of dynamic effects in these and other unimolecular reactions is discussed.
- Newmann-Evans, Richard H.,Simon, Reyna J.,Carpenter, B. K.
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p. 695 - 711
(2007/10/02)
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- SYNTHESIS OF β- AND γ-HYDROXY SULFONES BY REGIOSELECTIVE OPENING OF β,γ-EPOXY SULFONES
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β,γ-Epoxy sulfones 1 derived from allylic sulfones react regioselectively with organomagnesium compounds in the presence or not of catalytic amounts of copper(I) bromide to afford β-hydroxy sulfones 2 or γ-tosylated allylic alcoholates 5 respectively.The Michael type addition of Grignard reagents to intermediates 5 in the presence of catalytic amount of copper(I) bromide yields γ-hydroxy sulfones 6.The PCC oxidation of β- and γ-hydroxy sulfones give β- and γ-oxo sulfones 10 and 11 respectively.In the case of γ-oxo-sulfones their treatment with DBU affords α-substituted, α, β- unsaturated carbonyl compounds.
- Najera, Carmen,Sansano, Jose Miguel
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p. 3993 - 4002
(2007/10/02)
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- A Convenient One-flask Synthesis of α-Methylenealdehydes from Primary Alcohols
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A convenient one-flask synthesis of α-methylenealdehydes from primary alcohols has been established.
- Takano, Seiichi,Inomata, Kohei,Samizu, Kiyohiro,Tomita, Shun'ichi,Yanase, Masashi,et al.
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p. 1283 - 1284
(2007/10/02)
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- Oxidation of α-Methylstyrene to Phenylacrolein
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Various kinds of Mo-based oxides were tested as catalysts for the vapor-phase oxidation of α-methylstyrene to form phenylacrolein (atropoaldehyde).The best performance was obtained with the Te/Mo atomic ratio = 0.4 catalyst; the one-pass yield of phenylacrolein attained 48.5 molpercent at the α-methystyrene conversion of 96.3percent.
- AI, Mamoru
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p. 657 - 658
(2007/10/02)
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- REACTIVITY OF α-ARYLSELENO-ALDEHYDES TOWARDS HALOGENS AND BENZENESELENENYL CHLORIDE
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Chlorination of α-seleno-aldehydes bearing an α-hydrogen gives selenium dichlorides which decompose into α-chloro α-seleno-aldehydes and α-chloroenal.Bromination, in all cases, and chlorination for the other α-seleno-aldehydes lead to the α-halogenoaldehydes.
- Paulmier, Claude,Outurquin, Francis,Plaquevent, Jean-Christophe
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p. 5893 - 5896
(2007/10/02)
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- INDUCTION PAR LA LUMIERE DE L'OXYDATION DES COMPLEXES Η3-ALLYLPALLADIUM PAR L'OXYGENE MOLECULAIRE
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Irradiation at λ=366 nm of oxygenated solutions of η3-allylpalladium complexes leads to unsaturated carbonyl compounds.Substitution of the η3-allyl ligand by an electron withdrawing group could induce a regioselective oxidation of the allylic position farthest from this group.The efficiency of these reactions is sensible to the nature of the solvent.
- Muzart, J.,Pale, P.,Pete, J.P.,Riahi, A.
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p. 731 - 739
(2007/10/02)
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- AN EFFICIENT SYNTHESIS OF CHIRAL 2-(p-TOLYLSULFINYL)-2-BUTENOLIDES
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A high yield, two-step synthesis of enantiomerically pure 2-(p-tolylsulfinyl)-2-butenolides has been developed.The method is applicable to the preparation of butenolides having a variety of substituents in the 3-position.
- Holton, Robert A.,Kim, Hyeong-Baik
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p. 2191 - 2194
(2007/10/02)
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- Oxidation of Styrene Derivatives by S2O82--CuII in Acetic Acid and Acetonitrile. Reaction Paths in Oxidations via Radical Cations
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β-Aryl carbonyl compounds are major products in the oxidation of a variety of styrene derivatives by S2O82--CuII.Evidence is presented that they arise via oxidation to a radical cation, nucleophilic addition of water to give a β-hydroxyalkyl radical, CuII oxidation to epoxide, and finally acid-catalyzed rearrangement.Data on oxidation of alkyl aromatics with additional functional groups are presented.With ether and amino groups, oxidation occurs at the functional group even when it is remote from the aryl nucleus.These and previous data are summarized to give a coherent picture of the various paths by which aryl side chains may be degraded via initial radical cation intermediates.
- Walling, Cheves,El-Taliawi, Gamil M.,Amarnath, Kalyani
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p. 7573 - 7578
(2007/10/02)
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- Syntheses and Reactions of 3-Phenyloxete and the Parent Unsubstituted Oxete
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The elimination of p-toluenesulfonic acid and o-nitrophenylselenilic acid from substituted oxetanes gives 3-phenyloxete (6) and oxete (9), respectively. 3-Phenyloxete (6) undergoes the expected chemistry as well as a facile addition of triplet oxygen to g
- Friedrich, Louis E.,Lam, Patrick Yuk-Sun
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p. 306 - 311
(2007/10/02)
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- Reactivity of Carbonyl Oxides. Characteristic Nucleophilic Oxygen Atom Transfer from R2COO beside Electrophilic and Radical Reactions
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According to a MINDO/3 calculation, carbonyl oxide H2COO has a large contribution of zwitterionic structure 1a, which is not altered by phenyl substituent.The dye-sensitized photooxidation of diazomethanes in CH2Cl2 - MeOH afforded ca. 30percent yield of α-methoxy hydroperoxides as product from 1a and MeOH.Relative reactivities of various types of substrates toward the carbonyl oxide from diazofluorene and 1O2 have been determined.While benzene gave phenol in a low yield, substituted benzenes such as toluene or anisole yielded products by hydrogen atom abstraction on the side chain as a major reaction.Olefins gave a rather minor amount of epoxides; the predominant reaction was C-C cleavage or allylic hydrogen abstraction.The realtive reactivity with carbonyl oxide is in the order Ph2SO >> Ph2S > C = C > benzene, where C = C means α-methylstyrene.This order is in sharp contrast to the case of peroxy acid, Ph2S >> Ph2SO >> C = C, or to the order with acylperoxy radical, C = C >> Ph2S, Ph2SO.The above order with carbonyl oxide indicates a nucleophilic oxygen atom transfer as a characteristic reaction; this was clearly shown by the positive ρ value of +0.26 for substituted diphenyl sulfoxides.The reactivities of various substrates revealed that another characteristic reaction is hydrogen atom abstraction as a radical, and carbonyl oxides could be regarded as a rather poor electrophilic O-transfer agent.These features may be understood by representing carbonyl oxides as a resonance hybrid of R2C=O+-O- (1a) and R2C*-O-O* (1c).
- Sawaki, Yasuhiko,Kato, Hiroshi,Ogata, Yoshiro
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p. 3832 - 3837
(2007/10/02)
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- Mechanism of the Photoepoxidation with and Photodecarboxylation of α-Keto Acids
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The photooxidation of benzoylformic acid (1a) in benzene gave peroxybenzoic acid, hydrogen peroxide, and phenyl benzoate.The addition of α-methylstyrene to the oxidation system afforded the epoxide together with acetophenone as a C-C cleaved product, and the ester yield was significantly increased at the expense of the peracid.The photooxidation of 1a was not sensitized by methylene blue or other sensitizers, but was efficiently accelerated by pyridine or other weakly basic solvents such as ethers.Pyridine effectively catalyzed the photoepoxidation as well as the photodecarboxylation of 1a to benzaldehyde.The photoepoxidation gave predominantly trans epoxides, and the relative reactivities of olefins were similar to the photoepoxidation with benzoin (i.e., PhCO3.) and quite different from the peracid epoxidation.Similar results were obtained by other α-keto acids or the corresponding esters.These facts suggest that the photoepoxidation proceeds via radical epoxidation by acylperoxy radical, affording trans epoxide predominantly.Contrary to previous reports, the photooxidation of α-keto acids via an 1O2 reaction was not substantiated.The photodecarboxylation of 1a to afford benzaldehyde was selectively catalyzed by water, and its undissociated form was about tenfold more reactive than the corresponding carboxylate ion.
- Sawaki, Yasuhiko,Ogata, Yoshiro
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p. 6455 - 6460
(2007/10/02)
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