- Total synthesis of (+)-isomigrastatin
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(Chemical Equation Presented) Marginally stable natural products: The asymmetric total synthesis of the hydrolytically and thermally labile natural product (+)-isomigrastatin was demonstrated. The thermodynamic instability of a 2E-configured double bond in the context of this 12-membered macrolide was further demonstrated by phosphine-catalyzed isomerization to the 2Z configuration.
- Krauss, Isaac J.,Mandal, Mihirbaran,Danishefsky, Samuel J.
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Read Online
- The extremely low intrinsic reactivity of the P-(formylmethyl)triphenylphosphonium cation: An artefact due to strong covalent hydration of the carbonyl group
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The title cation is found to exhibit the lowest Marcus intrinsic reactivity known so far for a carbon acid; this situation is shown to reflect a rate-limiting hydration/ dehydration reaction of the aldehyde functionality.
- Moutiers,Peng,Peignieux,Pouet,Terrier
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Read Online
- Synthesis of N-substituted 2-[(1E)-alkenyl]-4-(1H)-quinolone derivatives as antimycobacterial agents against non-tubercular mycobacteria
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In an effort to improve biological activities and to examine antimycobacterial-lipophilicity relationships of 2-[(1E)-alkenyl)]-4-(1H)- quinolones, we have synthesized a series of 30 quinolones by introducing several alkyl groups, an alkenyl and an alkynyl group at N-1. All synthetic compounds were first tested in vitro against Mycobacterium smegmatis and the most active compounds (MIC values ~3.0-7.0 μM) were further examined against three other rapidly growing strains of mycobacteria using a microtiter broth dilution assay. The Clog P values of the synthetic compounds were calculated to provide an estimate of their lipophilicity. Compounds 18e, 19a and 19b displayed the most potent inhibitory effect against M. smegmatis mc2155 with an MIC value of ~1.5 μM, which was twenty fold and thirteen fold more potent than isoniazid and ethambutol, respectively. On the other hand, compounds 17e, 18e and 19a were most active against Mycobacterium fortuitum and Mycobacterium phlei with an MIC value of ~3.0 μM. In the human diploid embryonic lung cell line MRC-5 cytotoxicity assay, the derivatives showed moderate to strong cytotoxic activity. Although the antimycobacterial activity of our synthetic compounds could not be correlated with the calculated log P values, an increase in lipophilicity enhances the antimycobacterial activity and C 13-C15 total chain length at positions 1 and 2 is required to achieve optimal inhibitory effect against the test strains.
- Wube, Abraham A.,Bucar, Franz,Hochfellner, Christina,Blunder, Martina,Bauer, Rudolf,Hüfner, Antje
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Read Online
- Rh(iii)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienonesviaC(sp2)-H bond activation
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Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienonesviaRh(iii)-catalyzed C-H activation ofN-methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity. Furthermore, mechanistic studies of arylative cyclization and a gram-scale experiment are also presented.
- Chegondi, Rambabu,Jadhav, Sandip B.,Maurya, Sundaram,Navaneetha, N.
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supporting information
p. 13598 - 13601
(2021/12/23)
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- Catalytic Synthesis of 1 H-2-Benzoxocins: Cobalt(III)-Carbene Radical Approach to 8-Membered Heterocyclic Enol Ethers
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The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [CoII(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile and practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are involved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near-barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experimental observations, density functional theory (DFT) calculations, and spin trapping experiments.
- De Bruin, Bas,De Zwart, Felix J.,Li, Zirui,Mathew, Simon,Wolzak, Lukas A.,Zhou, Minghui
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supporting information
p. 20501 - 20512
(2021/12/03)
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- Copper-Catalyzed N-O Cleavage of α,β-Unsaturated Ketoxime Acetates toward Structurally Diverse Pyridines
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The copper-catalyzed [4 + 2] annulation of α,β-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.
- Ding, Xiaojuan,Duan, Jindian,Fang, Zheng,Guo, Kai,Li, Zhenjiang,Mao, Yiyang,Rong, Binsen,Xu, Gaochen,Zhang, Lei,Zhu, Ning
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supporting information
p. 2532 - 2542
(2020/03/13)
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- C(sp2)-H Bond Multiple Functionalization in Air for Construction of Tetrahydrocarbazoles with Continuous Quaternary Carbons and Polycyclic Diversification
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The C(sp2)-H function of indole ketone with diazo compound via a rhodium(II)-catalyzed intramolecular electrophilic trapping reaction under mild conditions in air was demonstrated. The established methodology provided a highly efficient approach for direct synthesis of mutisubstituted tetrahydrocarbazoles with continuous quaternary carbons. The resulting products facilitate further modification to conveniently construct tetrahydrocarbazoles with additional fused heterocyclic rings. By phenotypic screening, several products exhibit good anticancer bioctivities in osteosarcoma cell lines.
- Dong, Suzhen,Jia, Shikun,Liu, Shunying,Ni, Dan,Pi, Rou,Song, Longlong,Tang, Jie,Yang, Fan
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- Visible-light driven synthesis of polycyclic benzo[: D] [1,3]oxazocine from 2-aminochalcone
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Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.
- Chen, Junhan,Gao, Yu-Qi,He, Yu-Peng,Hou, Yi,Li, Ruoxin,Xie, Weiqing,Zhang, Sheng-Yong,Zhu, Liming
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supporting information
p. 6739 - 6742
(2020/07/13)
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- Heavier Carbonyl Olefination: The Sila-Wittig Reaction
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The Wittig reaction is one of the most versatile tools in the repertoire of organic chemists. Thus, a broad variety of carbonyl compounds can be converted to tailor-made alkenes with phosphorus ylides under mild conditions. However, no comparable reaction has been reported for silanones, the silicon congeners of ketones. Here, we demonstrate for the first time the successful application of the Wittig olefination to iminosilylsilanone 1. The selective formation of a series of silenes (R2Sia? CR2) via the sila-Wittig reaction revealed an unprecedented approach to otherwise elusive compounds. In addition, the highly reactive and zwitterionic nature of 1 was also susceptible to nucleophilic attacks and cycloaddition reactions by and with the phosphorus ylides. Our results therefore make another important contribution to discovering the differences and similarities between carbon and silicon.
- Reiter, Dominik,Frisch, Philipp,Szilvási, Tibor,Inoue, Shigeyoshi
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supporting information
p. 16991 - 16996
(2019/10/16)
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- Tandem Wittig Reaction-Ring Contraction of Cyclobutanes: A Route to Functionalized Cyclopropanecarbaldehydes
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An original tandem reaction consisting of a Wittig reaction-ring contraction process between α-hydroxycyclobutanone and phosphonium ylides has been developed. Highly functionalized cyclopropanecarbaldehydes are obtained in good to high yield.
- Aitken, David J.,Caboni, Pierluigi,Cuccu, Federico,Frongia, Angelo,Luridiana, Alberto,Secci, Francesco,Serusi, Lorenzo
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supporting information
(2019/10/08)
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- BICYCLIC IMIDAZOLE DERIVATIES USEFUL FOR THE TREATMENT OF RENAL DISEASE, CARDIOVASCULAR DISEASES AND FIBROTIC DISORDERS
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The present invention relates to compounds of formula I: and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5 and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 41-42
(2018/02/03)
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- Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
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Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β-unsaturated compounds bearing an electron-withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C?C bonds. α,β-Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two-electron-reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single-site replacement of a crucial Tyr residue with a non-protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee.
- Heckenbichler, Kathrin,Schweiger, Anna,Brandner, Lea Alexandra,Binter, Alexandra,Toplak, Marina,Macheroux, Peter,Gruber, Karl,Breinbauer, Rolf
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supporting information
p. 7240 - 7244
(2018/06/15)
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- Synthesis of Oxatricyclooctanes via Photoinduced Intramolecular Oxa-[4+2] Cycloaddition of Substituted o-Divinylbenzenes
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The photolysis of substituted o-divinylbenzenes promotes a one-step and metal-free conversion to oxatricycles at room temperature. Irradiation o-divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition to form oxacyclic derivatives.
- Liu, Qiang,Wang, Junlei,Li, Dazhi,Gao, Guo-Lin,Yang, Chao,Gao, Yuan,Xia, Wujiong
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p. 7856 - 7868
(2017/08/14)
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- Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
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An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.
- Wei, Hongbo,Li, Yun,Xiao, Ke,Cheng, Bin,Wang, Huifei,Hu, Lin,Zhai, Hongbin
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supporting information
p. 5974 - 5977
(2016/01/09)
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- INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents of formulas (l)/(ll)/(lll) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
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Paragraph 00161; 00162
(2015/02/25)
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- Total synthesis of isoquinocyclinone
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The total synthesis of the heptacyclic natural product isoquinocyclinone has been achieved. A Hauser annulation was used to assemble the anthraquinone core structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was prepared by alkyne addition to a lactone intermediate and subsequent Ni 0-mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and final intramolecular N-alkylation. Hauser annulation: An efficient total synthesis of isoquinocyclinone was achieved using a pentacyclic lactone as the key intermediate (see scheme). The pyrrolo-pyrrole substructure was elaborated by acetylide acylation, conversion of an O,O-acetal into an N,O-acetal, and intramolecular amidine alkylation.
- Dischmann, Mike,Frassetto, Timo,Breuning, M. André,Koert, Ulrich
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supporting information
p. 11300 - 11302
(2014/10/15)
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- Extending the stetter reaction with 1,6-acceptors
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Pace Stetter: A new N-heterocyclic carbene (NHC)-catalysed transformation is described-the intramolecular vinylogous Stetter reaction. This transformation can be effected with both thiazolium and triazolium-based catalysts, using aromatic and aliphatic aldehydes, employing α,β,γ,δ- unsaturated esters, ketones, phosphonates and N-acylpyrroles, and can be conducted enantioselectively (see scheme). Copyright
- Law, Katherine R.,McErlean, Christopher S. P.
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supporting information
p. 15852 - 15855
(2014/04/03)
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- Inner workings of a cinchona alkaloid catalyzed oxa-Michael cyclization: Evidence for a concerted hydrogen-bond-network mechanism
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Cinchona alkaloids catalyze the oxa-Michael cyclization of 4-(2-hydroxyphenyl)-2-butenoates to benzo-2,3-dihydrofuran-2-yl acetates and related substrates in up to 99 % yield and 91 % ee (ee=enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen-bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra-Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C-2 of the substrate shows that addition of RO-H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism-based specificity. A concerted hydrogen-bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α-carbanionic center of the product enolate. The importance of concerted hydrogen-bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4-additions. Secret of cyclization: The cinchona alkaloid catalyzed asymmetric oxa-Michael cyclization of 2′-hydroxyphenyl-2-butenoates to benzodihydrofurans proceeds by a highly enantio- and diastereoselective syn-specific addition mode (see scheme). Transition-state activation of the carbonyl group by hydrogen bonding to the catalyst is excluded. This represents a clear-cut demonstration of the importance of concerted hydrogen-bond network mechanisms in cinchona-based asymmetric organocatalysis. Copyright
- Hintermann, Lukas,Ackerstaff, Jens,Boeck, Florian
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supporting information
p. 2311 - 2321
(2013/04/10)
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- Novel catalysis in the internal nanocavity of polyamine dendrimer for intramolecular michael reaction
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Poly(propyleneimine) (PPI) dendrimers functionalized with C16 alkyl chains acted as efficient tertiary amine catalysts for an intramolecular Michael reaction. The substrate was accommodated in a reactive conformation within a sterically confined nanocavity consisting of regularly arranged tertiary amino groups of the PPI dendrimers.
- Maeno, Zen,Mitsudome, Takato,Mizugaki, Tomoo,Jitsukawa, Koichiro,Kaneda, Kiyotomi
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supporting information; experimental part
p. 801 - 803
(2012/09/22)
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- High-pressure accelerated asymmetric organocatalytic friedel-crafts alkylation of indoles with enones: Application to quaternary stereogenic centers construction
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An organocatalytic Friedel-Crafts alkylation of indoles with α,β-unsaturated ketones was found to be efficiently accelerated under high-pressure conditions with a low loading of chiral primary amine salts with good yield and enantioselectivity up to 90%. This approach also allows, for the first time, selected indole derivatives containing quaternary stereogenic centers to be obtained from prochiral β,β-disubstituted enones with an enantioselectivity up to 80%.
- Lyzwa, Dawid,Dudzinski, Krzysztof,Kwiatkowski, Piotr
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supporting information; scheme or table
p. 1540 - 1543
(2012/06/15)
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- Total synthesis of infectopyrone, aplysiopsenes A-C, ent-aplysiopsene D, phomapyrones A and D, 8,9-dehydroxylarone, and nectriapyrone
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The total synthesis of the 2-pyrone natural products nectriapyrone, aplysiopsenes A-C, ent-aplysiopsene D, phomapyrones A and D, and of 8,9-dehydroxylarone were achieved by Wittig olefination starting with vermopyrone. Infectopyrone was synthesized by Horner-Wadsworth-Emmons reaction starting with phomapyrone D. Racemic phomapyrone C methyl ether was obtained by hydrogenation of nectriapyrone. The total syntheses were achieved starting from commercially available 3,5-heptanedione and led to the desired natural products in 18-46% over 5-6 steps, whereupon all five-step syntheses were carried out with a single chromatographic workup. The total synthesis of infectopyrone, aplysiopsenes A-D, of phomapyrones A and D, and of 8,9-dehydroxylarone were achieved for the first time, giving unambiguous proof for the proposed structures of these natural products.
- Geiseler, Oliver,Podlech, Joachim
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experimental part
p. 7280 - 7287
(2012/09/11)
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- Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl- 4(1H)-quinolones
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A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11-13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0 mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure-activity relationships.
- Wube, Abraham A.,Hüfner, Antje,Thomaschitz, Christina,Blunder, Martina,Kollroser, Manfred,Bauer, Rudolf,Bucar, Franz
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experimental part
p. 567 - 579
(2011/03/17)
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- Stereoselective olefination of N-sulfonyl imines with stabilized phosphonium ylides for the synthesis of electron-deficient alkenes
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An unprecedented protocol has been developed for thestereoselective synthesis of structurally diverse electron-deficient alkenes in moderate to excellent yields from readily accessible N-sulfonyl imines and stabilized phosphonium ylides. Significantly, the olefination reaction of N-sulfonylimines with nitrile-stabilized phosphonium ylides affords an array of α,β-unsaturated nitriles with high Z selectivity, and the reactions with ester-, amide-, and ketone-stabilized phosphonium ylides afford α,β-unsaturated esters, amides, and ketones with high E selectivity, respectively. Spectroscopic analysis of the reaction mixtures and trapping of the intermediates allow plausible mechanisms to be proposed. Initialimine/ylide addition leads to the formation of betaines that cyclize to form 1,2-azaphosphetanes that subsequently eliminate iminophosphoranes to yield alkenes. For the synthesis of electron-deficient 1,2-disubstituted alkenes, the presence of an electron-withdrawing group in the betaine allows rapid interconversion between its two diastereomers through proton transfer. The Z/E selectivity for alkene synthesis is determined by the different rates at which the two betaine diastereomers form the corresponding 1,2-azaphosphetane diastereomers. In contrast, the Z/E selectivity for the synthesis of electron-deficient trisubstituted alkenes originates from the diastereoselective addition of stabilized phosphonium ylides to N-sulfonyl imines.
- Fang, Fan,Li, Yuan,Tian, Shi-Kai
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supporting information; experimental part
p. 1084 - 1091
(2011/04/15)
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- Diene-yne cyclisation reactions of 1-ethynyl-2-vinyl-3,4- dihydronaphthalenes and 1-ethynyl-2-vinylnaphthalenes
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The reaction of 1-ethynyl-2-vinyl-3,4-dihydronaphthalenes and 1-ethynyl-2-vinylnaphthalenes over RuCI2(p-cymene) PPh3 leads to 9,10-dihydrophenanthrenes and phenanthrenes in those cases where the ethynyl group in the substrates carries a terminal proton. When 1-phenylethynyl-2-vinyl-3,4-dihydronaphthalenes or 1-phenylethynyl-2- vinylnaphthalenes are reacted over Pt(PPh3)4, 1-methylene-1H-benz[e]-4,5-dihydroindenes and 1-methylene-1H-benz[e]indenes are formed.
- Watanabe, Masataka,Shiine, Kodai,Ldeta, Keiko,Matsumoto, Taisuke,Thiemann, Thies
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experimental part
p. 669 - 678
(2009/09/06)
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- Kinetic and mechanistic study on the thermal reactivity of stabilized phosphorus ylides, part 3: [(Acetyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and [(alkoxy-carbonyl) (arylcarbamoyl)-methylene] triphenylphosphoranes and their thiocarbamoyl analogues
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A series of five [(acety])(arylcarbabmoyl)methylene]triphenyl-phosphoranes 1a-e and their thiocarbamoyl analogues 2a-e, |(alkoxycarbonyl)(arylcarbamoyl) methylene]triphenylphosphoranes 3a-e and thiocarbamoyl analogues 4a-e were prepared and fully characterized. All ylides are found under conditions of flash vacuum pyrolysis to fragment giving arylisocyanate or isothiocyanate and acetyl ylides or alkoxy ylides which undergo thermal extrusion of Ph3PO. A kinetic study shows that these reactions are unimolecular and are of first-order nature with no significant substituent effect. The thiocarbamoyl ylides 2 react from 4.6 to 42 times faster than their carbamoyl ylides 1, while the thiocarbamoyl ylides 4 react from 6.6 to 20.9 times faster than their carbamoyl ylides 3.
- Aitken, R. Alan,Al-Awadi, Nouria A.,Dawson, Graham,El-Dusouqui, Osman,Kaul, Kamini,Kumar, Ajith
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- A convenient method for the preparation of α-vinylfurans by phosphine-initiated reactions of various substituted enynes bearing a carbonyl group with aldehydes
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α-Vinylfurans were obtained by phosphine-initiated cyclization of various enynes bearing a carbonyl group at the ene end in the presence of various aldehydes, in moderate to high yields. The reaction may consist of 1,6-addition of phosphine to the enynes, ring closure, and Wittig reaction between the ylid resulting from cyclization and an aldehyde. Thus, various aldehydes were able to be used in the reaction. The reaction was influenced greatly by the substituents at the acetylene position (R1) and the α-position of the carbonyl group (R3).
- Kuroda, Hirofumi,Hanaki, Emi,Izawa, Hironori,Kano, Michiko,Itahashi, Hiromi
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p. 1913 - 1920
(2007/10/03)
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- VITAMIN D ANALOGUES, COMPOSITIONS COMPRISING SAID ANALOGUES AND THEIR USE
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Compounds according to formula I: in which formula R1 and R2, which may be the same or different, represent halogen, (C1-C6) hydrocarbyl, optionally substituted with one or two hydroxyl group on one or more fluorine atoms, or, together with the carbon atom to which they are both attached, R1 and R2 form a (C3-C6)carbocyclic ring, or one of R1 and R2 taken together with R3 forms a direct bond, such that a triple bond is constituted, or R1 and R2 represent both hydrogen; R3 when not forming a direct bond with one of R1 and R2 represents hydrogen or (C1-C3)hydrocarbyl; X represents (E)-ethylene, (Z)-ethylene, ethynylene, or a bond; Y and Z independently represent hydrogen or methyl; the bond between C#16 and C#17 is depicted with a dotted line to illustrate that said bond may be either a single bond, in which case the projection of the ring substituents is beta, or a double bond; A represents hydroxyl, fluorine or hydrogen; B represents CH2 or H2; the configuration is the 3-position corresponds to the same configuration as in natural vitamine D3 (normal), or the configuration in the configuration in the 3-position is opposite to that of natural vitamin D3(epi); with the proviso that when X represents (E)-ethylene or (Z)-ethylene, one of R1 and R2 taken together with R3 may not form a direct bond, such that a triple bond is constituted; with the further proviso that when X represents a bond R1 ands R2 are nor hydrogen; with the further proviso that the compound of formula I is not 3(S)-hyroxy-9, 10-secocholesta-5(Z),7(E),10(19),22(E),24-penta-ene; and prodrugs and stereo isomeric forms thereof are provided together with their use in therapy, and their use in the manufacture of medicaments.
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- Antitumour polycyclic acridines. Part 13. Synthesis of 2-substituted 7H-pyrido[4,3,2-kl]acridines by thermolysis of 9-(5-alkyltriazol-1-yl)acridines
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Interaction of phosphoranylidene ketones with 9-azidoacridine in refluxing benzene affords 9-(5-substituted triazol-1-yl)acridines, which, on thermolysis in boiling diphenyl ether at 259 °C, yield 2-substituted 7H-pyrido[4,3,2-kl] acridines in high yields. These tetracyclic acridines are less potent inhibitors of human tumour cells in vitro than their pentacyclic analogues.
- Ellis, Michael J.,Stevens, Malcolm F. G.
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- Kinetics of proton transfer from phosphonium ions to electrogenerated bases: Polar, steric and structural influences on kinetic acidity and basicity
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Derivative cyclic voltammetry (DCV) and linear sweep voltammetry (LSV) have been used to measure rates of proton transfer in DMSO solution between different types of electrogenerated base (EGB) and a series of phosphonium ions of relevance to ylide formation for synthetic reactions. Although the electrochemical methods are convenient for the measurement of rates of proton transfer in these systems a major conclusion of the study is that considerable care must be exercised in the application of the methods and in drawing general conclusions from the results. In particular, comparison of kinetic acidity with thermodynamic pK values in DMSO shows that a single Bronsted relationship does not hold for the series of phosphonium ions. The kinetic acidities are profoundly affected by: whether the EGB is a carbon or nitrogen base; the propensity of some of the phosphonium ions to enolise; and steric factors. Other measures of electron-demand at the acidic methylene groups (13C and 1H chemical shifts, reduction potentials) are consistent with the pK(DMSO) values. The kinetic results confirm that the Ph3P+ group is, for non-enolisable phosphonium salts, more activating than Bu3P+.
- Bettencourt, Ana-Paula,Freitas, Ana Maria,Montenegro, M. Irene,Nielsen, Merete Folmer,Utley, James H. P.
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p. 515 - 522
(2007/10/03)
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- On the reaction of prop-2-enylidenetriphenylphosphorane derivatives. Novel synthesis of the azulene ring system
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Reaction of prop-2-enylidenetriphenylphosphorane derivatives with several tropones has been studied in an attempt to provide a short new route to the azulene ring system. (2-Ethoxyprop-2-enylidene)triphenylphosphorane 4 reacts with 2-chloro-, 2-methoxy- and 2,3,5,7-tetrachlorotropones 7a-c to give azulene derivatives 8 and 9 in moderate yields. On the other hand, reaction of [2-ethoxy-3-(ethoxycarbonyl)prop-2-enylidene]triphenylphosphorane 6 with tropones 7a,c results in the formation of azulene esters 10 and 11 in low yields, whilst that with tropone 7b gives no azulene and substrate 7b is recovered. In order to gain insight into the mechanistic pathways, reaction of phosphoranes 4 and 6 with deuteriated tropones 14a,b which are the corresponding trideuteriated derivatives of compounds 7a,b, have also been studied. Furthermore, compound 4 reacts also with 5-(dimethylaminomethylene)cyclopenta-1,3-dienecarbaldehyde 33 to give 6-ethoxyazulene 37 in moderate yield.
- Takayasu, Tohru,Nitta, Makoto
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p. 681 - 686
(2007/10/03)
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- Fluorinated abscisic acid derivatives and plant growth regulator thereof
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The present invention provides novel fluorinated abscisic acid derivative represented by formula of: STR1 wherein: X is O(CH2)2 O or O; and, R is hydroxymethyl, aldehyde, C1-2 alkoxycarbonyl or carboxyl group. The present invention also provides a novel process for preparing the fluorinated abscisic acid derivative represented as the formula (I), and also provides their use for plant growth regulator.
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- Synthesis and reactions of [1-(trialkylsilyl)alkylidene]triphenylphosphoranes
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Alkylidenetriphenylphosphoranes 1 react with trialkyl halosilanes 2 to afford silylated alkylidenephosphoranes 5, which can be converted to acylated alkylidenephosphoranes 8 and 10 by trimethylsilyl carboxylates 6 or carboxylic anhydrides 10. Bis(acylalkylidenephosphoranes) 13-15 are available from 5 and bis(trimethylsilyl) dicarboxylates 12 or cyclic or polymeric anhydrides 16, 17.
- Bestmann,Bomhard,Dostalek,Pichl,Riemer,Zimmermann
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p. 787 - 792
(2007/10/02)
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- A new synthesis of α-β-unsaturated ketones
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α,β-unsaturated ketones have been obtained by thermolysis of δ-hydroxy β-keto triphenylphosphoranes prepared from the corresponding β-keto phosphoranes.
- Le Roux,Le Corre
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p. 2591 - 2594
(2007/10/02)
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- The Synthesis of 4-Oxo-2-pentenoic Esters by Wittig Reaction Using α-Oxoesters
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The reaction of stabilized ylides with α-oxoesters gives high yields of 4-oxo-2-pentenoic esters.By suitable substitution of each reactant, highly substituted and hindered enones can be prepared in quantity, with excellent geometric selectivity.
- Schuda, Paul Francis,Ebner, Cynthia B.,Potlock, Steven J.
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p. 1055 - 1057
(2007/10/02)
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- Synthesis and Characterization of Palladium(II)-η3-Allyl-Ylide Complexes. X-Ray Crystal Structure of 3-2-MeC3H4)>
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The complexes 3-2-XC3H4)> have been obtained in high yields by treatment of the dimers 3-2-XC3H4)>2> with the keto-stabilized ylides Ph3PC(H)COMe and Ph3PC(H)COPh in CH2Cl2 solution.They have been characterized by analytical data, i.r., low temperature 1H and 31P- n.m.r. and for complex (2) also by 13C n.m.r. spectroscopy.Spectroscopic evidence indicates that complexes (1)-(4) in solution at low temperature are present as two diastereomeric forms arising from co-ordination on the metal centre of the assymetric ylidic carbon atom and of the η3-allyl ligand.In CH2Cl2 solution at room temperature the complexes are in equilibrium with their reagents.Reaction with PPh3 and Cl gives 3-2-XC3H4)(PPh3)> and 3-2-XC3H4)>, respectively, and the free ylide.The X-ray crystal structure of complex (2) was determined showing that, in the solid state, only one diastereomer is present.The crystals are monoclinic, space group P21/n with a = 9.668(3), b = 14.879(4), c = 16.226(3) Angstroem, β = 99.85(3) degree and Z = 4.Final full-matrix least-squares refinement, based on 3 063 reflections, converged to R = 0.031.The keto-stabilized ylide ligand is C bonded to the metal with a Pd-C distance of 2.193(3) Angstroem.
- Facchin, Giacomo,Bertani, Roberta,Calligaris, Mario,Nardin, Giorgo,Mari, Marina
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p. 1381 - 1388
(2007/10/02)
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- Cumulated Ylides, XVI. A Method for the Exchange of the OH Group in Free Carboxylic Acids by the Ylide Function
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Carboxylic acids 5 react with triphenylphosphorane (4) via the intermediate 6 with formation of the phosphoranes 7, which rearrange by heating in an intramolecular acyl migration to ylides 10.By heating of 10 in the presence of an alcohol 13 the acyl ylides 11 and urethanes 14 are formed.The reaction sequence allows the replacement of the OH group in carboxylic acids by the ylide function.
- Bestmann, Hans Juergen,Schade, Gerold,Schmid, Guenter,Moenius, Thomas
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p. 2635 - 2639
(2007/10/02)
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- JUVENILE HORMONE ANALOGS. PART XXII. SYNTHESIS OF 10-METHOXY-6,7-DIMETHYL-3-UNDECEN-2-ONE METHOXIME
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Description is given of the synthesis of the title compound, obtained for investigation on its biomimetic insect juvenile hormone activity.
- Biernacki, Wladyslaw,Gdula, Andrzej
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p. 1365 - 1368
(2007/10/02)
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- Novel esters of 2-methyl-3-allyl-4-substituted-cyclopent-2-ene-1-yl
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Novel esters of the formula STR1 wherein R1 and R2 are individually selected from the group consisting of carbamoyl and R1 ' and R2 ', R1 ' and R2 ' are individually selected from the group consisting of hydrogen, halogen, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, aralkyl of 7 to 13 carbon atoms, alkoxycarbonyl of 2 to 5 carbon atoms and --CN, R3 and R3 ' are individually selected from the group consisting of hydrogen, halogen, alkenyl of 2 to 3 carbon atoms and alkyl of 1 to 3 carbon atoms, Y' is selected from the group consisting of STR2 R4 ' and R5 ' are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, fluorine, bromine, chlorine and R4 ' and R5 ' together with the carbon atom to which they are attached form an optionally unsaturated hydrocarbon ring or heterocycle of 3 to 7 chain members and a heterocycle of the formula X is selected from the group consisting of sulfur and oxygen or R4 ' is cyano and R5 ' is phenyl or R4 ' is hydrogen and R5 ' is selected from the group consisting of cyano, STR3 AlK is alkyl of 1 to 4 carbon atoms, the double bond in the 1- position of the vinyl side chain of formula (A) having (E) or (Z) configuration, R6 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and alkoxycarbonyl of 2 to 5 carbon atoms, the substituents on the cyclopropane ring of formula (A) and (C) have the cis or trans, racemic or optically active configuration, Z1 is alkyl of 1 to 4 carbon atoms, Z2, Z3 and Z4 are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms and halogen and the asymetric carbon of formula (D) may be (S) or (R) configuration or a racemic mixture thereof and the carbon atom in the 1- position of the alcohol moiety may have (R), (S) or racemic configuration having insecticidal properties and their preparations.
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- ω-BROMOALKAPOLYENYLMETHYL KETONES-I. REACTION OF 5-BROMO-3-PENTEN-2-ONE WITH TRIPHENYLPHOSPHINE
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The reaction of (E)-5-bromo-3-penten-2-one with triphenylphosphine affords a 3:1 mixture of two protomeric phosphonium salts: 4-oxo-2-pentenyltriphenylphosphonium bromide and 4-oxo-1-pentenyltriphenylphosphonium bromide, characterized by the 13C NMR spectrum of the mixture.However, the common phosphorane of these salts gives two condensation products with benzaldehyde, corresponding to α- and γ-condensation respectively.
- Font, J.,March, P. de
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p. 2391 - 2396
(2007/10/02)
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- 3-(Substituted) vinyl cephalosporins
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New 3-(substituted) vinyl cephalosporin compounds, e.g., 3-(2'-ethoxycarbonylvinyl)-7-phenoxyacetamido-3-cephem-4-carboxylic acid, which are useful as antibiotics, and 3-(substituted) vinyl cephalosporin compounds which are useful as intermediates in preparing antibiotic substances.
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- Organic derivatives
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Propanoic acid derivatives of formula: STR1 where X represents a ketonic or hydroxylic function, R1 is a C1-8 alkyl group optionally substituted by hydroxy or --COOH and R2 is hydrogen or a protecting group, having spasmolytic activity.
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