- High-Throughput reaction optimisation and activity screening of ferrocene-based lewis acid-catalyst complexes by using continuous-flow reaction detection mass spectrometry
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Optimising synthetic conversions and assessing catalyst performance is a tedious and laborious endeavour. Herein, we present an automated alternative to the commonly applied sequential approaches that are used to increase catalyst discovery process efficiencies by increasing the number of entities that can be tested. This new approach combines conversion of the reactants and determination of product formation into a single comprehensive reaction detection system that can be operated with minimal catalyst and reactant consumption. With this approach, rudimentary reaction conditions can be quickly optimised and the same system can then be used to screen for the optimal homogenous catalyst in a selected solution-phase synthetic conversion. The system, which is composed of standard HPLC components, can be used to screen catalyst libraries at a repetition rate of five minutes and can be run unsupervised. The sensitive mass spectrometric detection that is implemented in the reaction detection methodology can be used for the simultaneous monitoring of reactants, catalysts and product ions. In the experiments, the three-component reaction that gives a substituted 2imidazoline was optimised. Afterwards, the same method was used to assess a library of ferrocene-based Lewis acid catalysts for performance in the aforementioned conversion in six different solvents. We demonstrate the feasibility of using this methodology to directly compare the performance results obtained in different solvents by calibrating the solvent-specific MS responses.
- Martha, Cornelius T.,Heemskerk, Anton,Hoogendoorn, Jan-Carel,Elders, Niels,Niessen, Wilfried M. A.,Orru, Romano V. A.,Irth, Hubertus
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Read Online
- Modular Photocatalytic Synthesis of α-Trialkyl-α-Tertiary Amines
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Molecules displaying an α-trialkyl-α-tertiary amine motif provide access to an important and versatile area of biologically relevant chemical space but are challenging to access through existing synthetic methods. Here, we report an operationally straightforward, multicomponent protocol for the synthesis of a range of functionally and structurally diverse α-trialkyl-α-tertiary amines, which makes use of three readily available components: dialkyl ketones, benzylamines, and alkenes. The strategy relies on the of use visible-light-mediated photocatalysis with readily available Ir(III) complexes to bring about single-electron reduction of an all-alkyl ketimine species to an α-amino radical intermediate; the α-amino radical undergoes Giese-type addition with a variety of alkenes to forge the α-trialkyl-α-tertiary amine center. The mechanism of this process is believed to proceed through an overall redox neutral pathway that involves photocatalytic redox-relay of the imine, generated from the starting amine-ketone condensation, through to an imine-derived product. This is possible because the presence of a benzylic amine component in the intermediate scaffold drives a 1,5-hydrogen atom transfer step after the Giese addition to form a stable benzylic α-amino radical, which is able to close the photocatalytic cycle. These studies detail the evolution of the reaction platform, an extensive investigation of the substrate scope, and preliminary investigation of some of the mechanistic features of this distinct photocatalytic process. We believe this transformation will provide convenient access to previously unexplored α-trialkyl-α-tertiary amine scaffolds that should be of considerable interest to practitioners of synthetic and medicinal chemistry in academic and industrial institutions.
- Gaunt, Matthew J.,Harris, Georgia R.,Henry Blackwell, J.,Smith, Milo A.
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p. 15946 - 15959
(2021/10/12)
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- Poisoning effect of N-containing compounds on performance of Raney nickel in transfer hydrogenation
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The effect of amines, imines and heterocycle compounds on conversion has been studied in transfer hydrogenation of camphor and 2-PrOH catalyzed by Raney nickel. Small amount (5 mol% to nickel) of N-containing compound significantly decreases catalyst activity. It has been shown that the poisoning effect mostly depends on molecular size of amines and heterocyclic compounds. For aniline and cyclohexylamine the dependence of camphor conversion on poison/nickel ratio was obtained. Additionally, benzaldehyde, cinnamaldehyde demonstrated higher reactivity compared corresponding imines under transfer hydrogenation conditions. Obtained data explain low activity of nickel-based catalysts when N-containing compounds are presented in reaction mixture.
- Martyanov, Oleg N.,Philippov, Alexey A.
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- Nucleophilic Imines and Electrophilic o-Quinone Methides, a Three-Component Assembly of Assorted 3,4-Dihydro-2 H-1,3-benzoxazines
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A one-pot method for joining three separate components leading to an assortment of N-substituted 3,4-dihydro-2H-1,3-benzoxazines is described. The method involves the addition of a Grignard reagent to an o-OBoc salicylaldehyde in the presence of an imine. With a variety of components, 15 examples are presented, including the diastereoselective incorporation of chiral imines.
- Chen, Peishan Kc,Wong, Yuk Fai,Yang, Derek,Pettus, Thomas R. R.
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supporting information
p. 7746 - 7749
(2019/10/11)
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- Ru-Catalyzed Transfer Hydrogenation of Nitriles, Aromatics, Olefins, Alkynes and Esters
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This paper reports the preparation of new ruthenium(II) complexes supported by a pyrazole-phosphine ligand and their application to transfer hydrogenation of various substrates. These Ru complexes were found to be efficient catalysts for the reduction of nitriles and olefins. Heterocyclic compounds undergo transfer hydrogenation with good to moderate yields, affording examples of unusual hydrogenation of all-carbon-rings. Internal alkynes with bulky substituents show selective reduction to olefins with the unusual E–selectivity. Esters with strong electron-withdrawing groups can be reduced to the corresponding alcohols, if ethanol is used as the solvent. Possible mechanisms of hydrogenation and olefin isomerization are suggested on the basis of kinetic studies and labelling experiments.
- Alshakova, Iryna D.,Gabidullin, Bulat,Nikonov, Georgii I.
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p. 4860 - 4869
(2018/10/02)
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- Asymmetric Synthesis of Six-Membered Cyclic Sulfamides via Palladium-Catalyzed Alkene Carboamination Reactions
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The asymmetric synthesis of six-membered cyclic sulfamides via palladium-catalyzed alkene carboamination reactions of N -homoallylsulfamides with aryl halides is described. High levels of enantioselectivity were obtained with a catalyst composed of Pd 2 dba 3 and (S)-Siphos-PE.
- Garlets, Zachary J.,Wolfe, John P.
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p. 4444 - 4452
(2018/05/28)
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- Optimum bifunctionality in a 2-(2-pyridyl-2-ol)-1,10-phenanthroline based ruthenium complex for transfer hydrogenation of ketones and nitriles: Impact of the number of 2-hydroxypyridine fragments
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Considerable differences in reactivity and selectivity for 2-hydroxypyridine (2-HP) derived ruthenium complexes in transfer hydrogenation are described. Bifunctional Ru(ii)-(phenpy-OH) [phenpy-OH: 2-(2-pyridyl-2-ol)-1,10-phenanthroline] complex (2) exhibited excellent catalytic activity in transfer hydrogenation (TH) of ketones and nitriles. Notably, in comparison with all the reported 2-hydroxypyridine (2-HP) derived ruthenium complexes in transfer hydrogenation, complex 2 displayed significantly higher activity. Additionally, exploiting the metal-ligand cooperativity in complex 2, chemoselective TH of ketones was achieved and sterically demanding ketones were readily reduced. An outer-sphere mechanism is proposed for this system as exogenous PPh3 has no significant effect on the rate of this reaction. This is a rare example of a highly active bifunctional Ru(ii) catalyst bearing only one 2-HP unit.
- Paul, Bhaskar,Chakrabarti, Kaushik,Kundu, Sabuj
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supporting information
p. 11162 - 11171
(2016/07/16)
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- Transfer Hydrogenation of Nitriles, Olefins, and N-Heterocycles Catalyzed by an N-Heterocyclic Carbene-Supported Half-Sandwich Complex of Ruthenium
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In the presence of KOBut, N-heterocyclic carbene-supported half-sandwich complex [Cp(IPr)Ru(pyr)2][PF6] (3) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) catalyzes transfer hydrogenation (TH) of nitriles, activated N-heterocycles, olefins, and conjugated olefins in isopropanol at the catalyst loading of 0.5%. The TH of nitriles leads to imines, produced as a result of coupling of the initially formed amines with acetone (produced from isopropanol), and showed good chemoselectivity. Reduction of N-heterocycles occurs for activated polycyclic substrates (e.g., quinoline) and takes place exclusively in the heterocycle. The TH also works well for linear and cyclic olefins but fails for trisubstituted substrates. However, the C = C bond of α,β-unsaturated esters, amides, and acids is easily reduced even for trisubstituted species, such as isovaleriates. Mechanistic studies suggest that the active species in these catalytic reactions is the trihydride Cp(IPr)RuH3 (5), which can catalyze these reactions in the absence of any base. Kinetic studies are consistent with a classical inner sphere hydride-based mechanism of TH.
- Mai, Van Hung,Nikonov, Georgii I.
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supporting information
p. 943 - 949
(2016/05/09)
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- Long-chain NHC-stabilized RuNPs as versatile catalysts for one-pot oxidation/hydrogenation reactions
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The synthesis and catalytic activity of long-chain NHC-stabilized RuNPs are presented. Full characterization of these novel nanostructures including surface state studies show that the ligand influences the number and the location of Ru active sites which impacts the NP catalytic activity, especially in hydrogenation reactions. The high stability and versatility of these nanosystems make them successful catalysts for both oxidation and hydrogenation reactions that can even be performed successively in a one pot-fashion.
- Martínez-Prieto,Ferry,Rakers,Richter,Lecante,Philippot,Chaudret,Glorius
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supporting information
p. 4768 - 4771
(2016/04/09)
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- NITROGEN-CONTAINING SATURATED HETEROCYCLIC COMPOUND
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The present invention provides a compound represented by the following formula (I) or its pharmaceutically acceptable salt: [wherein, R1 represents optionally substituted C1-4 alkyl, n shows integer of 1 to 4, R2 represents optionally substituted C1-4 alkyl or hydrogen atom, R3 represents optionally substituted C1-4 alkyl, R4a, R4b, R4c, and R4d, similarly or differently, represent optionally substituted C6-14 aryl, optionally substituted C1-4 alkyl, or hydrogen atom and the like, A represents optionally substituted C6-14 aryl or optionally substituted 5 to 11 membered heteroaryl].
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Paragraph 0348-0350
(2016/08/29)
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- Application of tris(trimethylsilyl) phosphite as a convenient phosphorus nucleophile in the direct synthesis of tetrasubstituted α-aminophosphonic acids from ketimines
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The condensation of tris(trimethylsilyl) phosphite with various ketimines leads directly to tetrasubstituted a-aminophosphonic acids. The presented reaction proceeds readily at room temperature and provides labile silylated esters of tetrasubstituted a-aminophosphonic acids, as non-isolable reaction intermediates. Subsequent methanolysis of the latter provides the desired á-aminophosphonic acids bearing an fully substituted á-carbon in good overall yields as crystalline non-hygroscopic solids after simple recrystallization from a methanol-acetone mixture.nordstom.
- Boduszek, Bogdan,Olszewski, Tomasz K.
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p. 173 - 179
(2017/03/06)
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- Transfer hydrogenation of ketones, nitriles, and esters catalyzed by a half-sandwich complex of ruthenium
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Half-sandwich complexes [Cp(PiPr3)Ru(CH3CN)2]PF6 (1; Cp = cyclopentadienyl) and [Cp(phen)Ru(CH3CN)]PF6 (2; Cp = pentamethylcyclopentadienyl, phen = phenanthroline) catalyse the transfer hydrogenation of ketones to alcohols, aldimines to amines, and nitriles to imines under mild conditions. In the latter process, the imine products come from the coupling of the amines formed initially with acetone derived from the reducing solvent (isopropanol). Among functionally substituted nitriles, the aldo and keto groups are reduced concomitantly with the cyano group, whereas ester and amido groups are tolerated. Amides and alkyl esters are not reduced under these conditions even upon heating to 70°C. However, phenylbenzoates and trifluoroacetates are reduced to alcohols. Kinetic studies on the reduction of acetophenone in isopropanol established that the reaction is first order in both the substrate and the alcohol. Stoichiometric mechanistic studies showed the formation of a hydride species. A hydride mechanism was proposed to account for these observations.
- Lee, Sun-Hwa,Nikonov, Georgii I.
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p. 107 - 113
(2015/01/30)
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- Tuneable hydrogenation of nitriles into imines or amines with a ruthenium pincer complex under mild conditions
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The selective hydrogenation of aromatic and aliphatic nitriles into amines and imines is described. Using a ruthenium pincer complex, the selectivity towards amines or imines can be controlled by simple parameter changes. The reactions are conducted under very mild conditions between 50-100°C at 0.4 MPa H2 pressure without any additives at low catalytic loadings of 0.5-1 mol %, which results in quantitative conversions and high selectivity.
- Choi, Jong-Hoo,Prechtl, Martin H. G.
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p. 1023 - 1028
(2015/03/18)
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- Synthesis of imines from amines in aliphatic alcohols on Pd/ZrO2 catalyst under ambient conditions
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Synthesis of imines from amines and aliphatic alcohols (C 1-C6) in the presence of base on supported palladium nanoparticles has been achieved for the first time. The catalytic system shows high activity and selectivity in open air at room temperature.
- Cui, Wenjing,Zhaorigetu, Bao,Jia, Meilin,Ao, Wulan,Zhu, Huaiyong
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p. 2601 - 2604
(2014/01/06)
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- Spirocyclic dihydropyridines by electrophile-induced dearomatizing cyclization of N-alkenyl pyridinecarboxamides
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On treatment with acylating or sulfonylating agents, N-alkenyl pyridine carboxamides (N-pyridinecarbonyl enamines) undergo a dearomatizing cyclization initiated by pyridine acylation and followed by intramolecular trapping of the resulting pyridinium cation. The products are spirocyclic dihydropyridines which may be further elaborated to spirocyclic heterocycles with drug-like features.
- Senczyszyn, Jemma,Brice, Heloise,Clayden, Jonathan
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supporting information
p. 1922 - 1925
(2013/06/04)
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- FUSED IMIDAZOLE DERIVATIVE HAVING TTK INHIBITORY ACTION
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Provided are a compound represented by general formula (1) and having a TTK inhibitory action and a medicine containing the compound. In formula (1), (X, Y, V, W) is (—N═, ═CR1—, ═N—, —CR7═), (—CR2═, ═N—, ═N—, —CR7═), etc.; A is an (un)substituted aromatic hydrocarbon ring, etc.; L is a single bond, —C(═O)—NRA—, etc.; Z is a group represented by the formula —NR3R4 or a group represented by the formula —OR5; R1 to R3, R6, and R7 each is a hydrogen atom, etc.; R4 and R5 each is an (un)substituted alkyl, etc.; and R8 is an (un)substituted cycloalkyl, etc.
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Page/Page column 95-96
(2012/03/26)
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- N-ACYL PYRIDINE BIARYL COMPOUNDS AND THEIR USES
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The present invention provides a compound of general formula:wherein Z2-Z6 include one or two nitrogen atoms as described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.
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Page/Page column 173
(2012/08/08)
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- N-ACYL PYRIMIDINE BIARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
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The present invention provides a compound of the general formula (1): wherein one of X and Y is N and the other is an optionally substituted carbon atom, and Z2-Z5 represent one or two nitrogen atoms, as further described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals and as components of pharmaceutical compositions. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds described herein or pharmaceutical compositions comprising such compounds.
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Page/Page column 216
(2012/08/08)
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- Enantioselective construction of bridged multicyclic skeletons: Intermolecular [2+2+2] cycloaddition/intramolecular diels-alder reaction cascade
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Bridging a gap: A cationic rhodium(I)/ligand complex catalyzes the title reaction of alkynes and amide-linked 1,5-dienes, leading to bridged multicyclic compounds, with high chemo-, regio-, and enantioselectivity (see scheme; Bn=benzyl).
- Kobayashi, Masayuki,Suda, Takeshi,Noguchi, Keiichi,Tanaka, Ken
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supporting information; experimental part
p. 1664 - 1667
(2011/03/22)
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- PYRAZINYLPYRIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
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The present invention provides a compound of Formula (I) and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.
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Page/Page column 99
(2011/04/14)
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- Selective formation of imines by aerobic photocatalytic oxidation of amines on TiO2
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An oxygenation pathway: The title transformation involves a two-step process: a selective oxygenation step to generate aldehyde intermediates and a subsequent condensation step to afford the imine products (see scheme).
- Lang, Xianjun,Ji, Hongwei,Chen, Chuncheng,Ma, Wanhong,Zhao, Jincai
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supporting information; scheme or table
p. 3934 - 3937
(2011/05/15)
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- Pyridine Classical Cannabinoid Compounds and Related Methods of Use
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Disclosed are compounds of the formula I: wherein R1, R2, V, W, X, Y and Z can be as defined herein. The compounds can be used in the treatment of disorders mediated by the cannabinoid receptors.
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Page/Page column 6-7
(2009/12/05)
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- Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium-mediated SN2′ cyclizations
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(Chemical Equation Presented) A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO 2Me) SN2′ cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.
- Banfi, Luca,Basso, Andrea,Cerulli, Valentina,Guanti, Giuseppe,Riva, Renata
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p. 1608 - 1611
(2008/09/16)
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- Convergent and rapid assembly of substituted 2-pyridones through formation of N-alkenyl alkynylamides followed by gold-catalyzed cycloisomerization
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(Chemical Equation Presented) A new method for the convergent and rapid assembly of substituted 2-pyridones was developed through the formation of N-alkenyl alkynylamides (amide-linked 1,5-enynes) by N-acylation of !mines with alkynoyl chlorides and the subsequent cationic Au(l)/PPh3-catalyzed cycloisomerization.
- Imase, Hidetomo,Noguchi, Keiichi,Hirano, Masao,Tanaka, Ken
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supporting information; experimental part
p. 3563 - 3566
(2009/05/07)
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- 2,4,5-Trisubstituted thiazole building blocks by a novel multi-component reaction
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A novel multi-component reaction (MCR) of oxo-components, primary amines, thiocarboxylic acids and 3-bromo-2-isocyanoacrylates yielding 2,4,5-trisubstituted thiazole building blocks is described.
- Umkehrer, Michael,Kolb, Jürgen,Burdack, Christoph,Hiller, Wolfgang
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- A simple and inexpensive method for the preparation of imines and azadienes
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A number of imines and azadienes were prepared in high yield and good purity by using the condensation reactions of various aldehydes and ketones with amines over natural Algerian bentonite.
- Saoudi,Benguedach,Benhaoua
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p. 2349 - 2354
(2007/10/02)
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- 13 C shieldings in syn and anti aldimines and ketimines
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The 13 C chemical shifts in a variety of aldimines and in both acyclic and cyclic ketimines have been examined.A comparison of the shieldings at the α carbons in syn versus anti stereoisomers shows a consistent upfield shift of 8-11 ppm in the syn isomer.The greater magnitude found in imines vs. oximes or hydrazones is a clear indication of a steric origin for the differential shieldings.The shifts in the imines of cyclohexanones exhibited stereochemically dependent effects of methyl substitution, very similar to those in analogous oxime and hydrazone derivatives.Chemical shift differences in the syn isomers of the α-phenetylimines of chiral aldimines and ketimines allow a facile measurement of diastereomer ratios for such compounds.
- Fraser, Robert R.,Banville, Jacques,Akiyama, Fuminori,Chuaqui-Offermanns, Noemi
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p. 705 - 709
(2007/10/02)
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