- An improved synthesis of β-Nicotyrine from the dehydrogenation of nicotine: Comparison of conventional and microwave-assisted reactions
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β-Nicotyrine, a minor tobacco alkaloid, can be rapidly prepared in good yield from the dehydrogenation of S-(-)-nicotine over MnO2 with microwave irradiation. This method is superior to dehydrogenation reactions that utilize S-(-)-nicotine and MnO2 in a variety of solvents under reflux.
- Wei, Xiaochen,Crooks, Peter A.
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- Interconversion of nicotine enantiomers during heating and implications for smoke from combustible cigarettes, heated tobacco products, and electronic cigarettes
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Physiological properties of (R)-nicotine have differences compared with (S)-nicotine, and the subject of (S)- and (R)-nicotine ratio in smoking or vaping related items is of considerable interest. A Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method for the analysis of (S)- and (R)-nicotine has been developed and applied to samples of nicotine from different sources, nicotine pyrolyzates, several types of tobacco, smoke from combustible cigarettes, smoke from heated tobacco products, e-liquids, and particulate matter obtained from e-cigarettes aerosol. The separation was achieved on a Chiracel OJ-3 column, 250 × 4.6 mm with 3-μm particles using a nonaqueous mobile phase. The detection was performed using atmospheric pressure chemical ionization (APCI) in positive mode. The only transition measured for the analysis of nicotine was 163.1 → 84.0. The method has been summarily validated. For the analysis, the samples of tobacco and smoke from combustible cigarettes were subject to a cleanup procedure using solid phase extraction (SPE). It was demonstrated that nicotine upon heating above 450°C for several minutes starts decomposing, and some formation of (R)-enantiomer from a sample of 99% (S)-nicotine is observed. An analogous process takes place when a 99% (R)-nicotine is heated and forms low levels of (S)-nicotine. This interconversion has the effect of slightly increasing the content of (R)-nicotine in smoke compared with the level in tobacco for combustible cigarettes and for heated tobacco products. The (S)/(R) ratio of nicotine enantiomers in e-liquids was identical with the ratio for the particulate phase of aerosols generated by e-cigarette vaping.
- Moldoveanu, Serban C.
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p. 667 - 677
(2022/02/02)
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- C2-Selective silylation of pyridines by a rhodium-aluminum complex
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We have developed a C2-selective mono-silylation of a variety of pyridines using a Rh-Al complex. Both the site- and mono-selectivity are controlledviathe pyridine coordination to the Lewis-acidic Al center prior to the activation of the pyridine C(2)-H bond at the proximal Rh center. A reaction mechanism is proposed based on several mechanistic studies, including the isolation of a (2-pyridyl)silylrhodium intermediate.
- Hara, Naofumi,Uemura, Nao,Nakao, Yoshiaki
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supporting information
p. 5957 - 5960
(2021/06/18)
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- Copper catalysed Gomberg-Bachmann-Hey reactions of arenediazonium tetrafluoroborates and heteroarenediazonium o-benzenedisulfonimides. Synthetic and mechanistic aspects
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Gomberg-Bachmann-Hey reactions were carried out in the presence of copper as a catalyst and gave rise to biaryls or heterobiaryls in good yields and in mild reaction conditions. A computational study of some key points of the reaction was performed. The results are coherent with the experimental data and confirm some aspects of the mechanism. The reaction free energies for the reduction in benzene by CuI of a set of 40 (hetero)arenediazonium tetrafluoroborates were calculated. Both the experiments and the calculations showed that in the coupling with substituted solvents (toluene, bromobenzene, nitrobenzene and anisole) the binding to the ortho position was always favoured.
- Antenucci, Achille,Barbero, Margherita,Dughera, Stefano,Ghigo, Giovanni
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- A case of chain propagation: α-aminoalkyl radicals as initiators for aryl radical chemistry
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The generation of aryl radicals from the corresponding halides by redox chemistry is generally considered a difficult task due to their highly negative reduction potentials. Here we demonstrate that α-aminoalkyl radicals can be used as both initiators and chain-carriers for the radical coupling of aryl halides with pyrrole derivatives, a transformation often employed to evaluate new highly reducing photocatalysts. This mode of reactivity obviates for the use of strong reducing species and was also competent in the formation of sp2 C-P bonds. Mechanistic studies have delineated some of the key features operating that trigger aryl radical generation and also propagate the chain process.
- Constantin, Timothée,Juliá, Fabio,Leonori, Daniele,Sheikh, Nadeem S.
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p. 12822 - 12828
(2020/12/29)
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- UVA- and Visible-Light-Mediated Generation of Carbon Radicals from Organochlorides Using Nonmetal Photocatalyst
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Carbon radicals are reactive species useful in various organic transformations. The C-X bond cleavage of organohalides by photoirradiation is a common method to generate carbon radicals in a controlled fashion. The use of organochloride substrates is still a formidable challenge due to the low reduction potential and the high dissociation energy of the C-Cl bond. In this report, we address these issues by using a nonmetal organic molecule with a relatively simple structure as a photocatalyst. In this catalyst (bis(dimethylamino)carbazole), the amino groups increase both the HOMO and LUMO energy levels, especially in the former. As a result, compared to the parent molecule, the new catalyst shows experimentally red-shifted absorption in the visible region and forms an excited state with better reducing capability. This photocatalyst was used in the reduction of unactivated aryl chlorides and alkyl chlorides in the presence of hydrogen atom donor at room temperature. The catalytic system can also be applied to the coupling of aryl chlorides with electron-rich arene and heteroarenes to affect the C-C bond-forming reactions. Our mechanistic study results support the assumption that carbon radicals are formed from the organochlorides via a single-electron-transfer step.
- Matsubara, Ryosuke,Yabuta, Tatsushi,Md Idros, Ubaidah,Hayashi, Masahiko,Ema, Fumitoshi,Kobori, Yasuhiro,Sakata, Ken
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p. 9381 - 9390
(2018/07/25)
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- A general copper-based photoredox catalyst for organic synthesis: Scope, application in natural product synthesis and mechanistic insights
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Organic transformations can broadly be classified into four categories including cationic, anionic, pericyclic and radical reactions. While the last category has been known for decades to provide remarkably efficient synthetic pathways, it has long been hampered by the need for toxic reagents, which considerably limited its impact on chemical synthesis. This situation has come to an end with the introduction of new concepts for the generation of radical species, photoredox catalysis – which simply relies on the use of a catalyst that can be activated upon visible light irradiation – certainly being the most efficient one. The state-of-the-art catalysts mostly rely on the use of ruthenium and iridium complexes and organic dyes, which still considerably limits their broad implementation in chemical processes: alternative readily available catalysts based on inexpensive, environmentally benign base metals are therefore strongly needed. Furthermore, expanding the toolbox of methods based on photoredox catalysis will facilitate the discovery of new light-mediated transformations. This article details the use of a simple copper complex which, upon activation with blue light, can initiate a broad range of radical reactions.
- Deldaele, Christopher,Michelet, Bastien,Baguia, Hajar,Kajouj, Sofia,Romero, Eugenie,Moucheron, Cecile,Evano, Gwilherm
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p. 621 - 629
(2018/10/04)
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- Dichromatic Photocatalytic Substitutions of Aryl Halides with a Small Organic Dye
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Photocatalytic bond activations are generally limited by the photon energy and the efficiency of energy and electron transfer processes. Direct two-photon processes provide sufficient energy but the ultra-short lifetimes of the excited states prohibit chemical reactions. The commercial dye 9,10-dicyanoanthracene enabled photocatalytic aromatic substitutions of non-activated aryl halides. This reaction operates under VIS-irradiation via sequential photonic, electronic, and photonic activation of the simple organic dye. The resultant highly reducing excited photocatalyst anion readily effected C?H, C?C, C?P, C?S, and C?B bond formations. Detailed synthetic, spectroscopic, and theoretical studies support a biphotonic catalytic mechanism.
- Neumeier, Michael,Sampedro, Diego,Májek, Michal,de la Pe?a O'Shea, Víctor A.,Jacobi von Wangelin, Axel,Pérez-Ruiz, Raúl
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supporting information
p. 105 - 108
(2017/12/04)
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- A General Copper Catalyst for Photoredox Transformations of Organic Halides
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A broadly applicable copper catalyst for photoredox transformations of organic halides is reported. Upon visible light irradiation in the presence of catalytic amounts of [(DPEphos)(bcp)Cu]PF6 and an amine, a range of unactivated aryl and alkyl halides were shown to be smoothly activated through a rare Cu(I)/Cu(I)?/Cu(0) catalytic cycle. This complex efficiently catalyzes a series of radical processes, including reductions, cyclizations, and direct arylation of arenes.
- Michelet, Bastien,Deldaele, Christopher,Kajouj, Sofia,Moucheron, Cécile,Evano, Gwilherm
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supporting information
p. 3576 - 3579
(2017/07/17)
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- Quantum Dots in Visible-Light Photoredox Catalysis: Reductive Dehalogenations and C-H Arylation Reactions Using Aryl Bromides
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In the recent past, visible-light-mediated photoredox catalysis has made a huge impact on the development of new synthetic methods under very mild and ecologically benign conditions. Although semiconductor nanocrystals or quantum dots (QDs) possess suitable optoelectronic and redox properties for photoredox catalytic applications, surprisingly, their use for the activation of challenging chemical bonds in the synthesis of organic molecules is little explored. We report here the application of ZnSe/CdS core/shell QDs for the synthetically important photoredox catalytic activation of carbon-halogen bonds in dehalogenation and C-H arylation reactions using (hetero)aryl halides as bench-stable inexpensive bulk starting materials, under very mild reaction conditions. The outstanding catalytic activity of ZnSe/CdS core/shell QDs is a direct consequence of the high specific surface area and homogeneity of QDs in solution and their high photostability toward oxidation.
- Pal, Anuushka,Ghosh, Indrajit,Sapra, Sameer,K?nig, Burkhard
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p. 5225 - 5231
(2017/07/04)
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- Chromoselective Photocatalysis: Controlled Bond Activation through Light-Color Regulation of Redox Potentials
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Catalysts that can be regulated in terms of activity and selectivity by external stimuli may allow the efficient multistep synthesis of complex molecules and pharmaceuticals. Herein, we report the light-color regulation of the redox potential of a photocatalyst to control the activation of chemical bonds. Light-color control of the redox power of a photocatalyst introduces a new selectivity parameter to photoredox catalysis: Instead of changing the catalyst or ligand, alteration of the color of the visible-light irradiation adjusts the selectivity in catalytic transformations. By using this principle, the selective activation of aryl–halide bonds for C?H arylation and the sequential conversion of functional groups with different reduction potentials is possible by simply applying different colors of light for excitation of the photocatalyst.
- Ghosh, Indrajit,K?nig, Burkhard
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supporting information
p. 7676 - 7679
(2016/07/07)
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- Synthesis of heteroarenes dyads from heteroarenes and heteroarylsulfonyl chlorides via Pd-catalyzed desulfitative C-H bond heteroarylations
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We report herein on the palladium-catalyzed direct heteroarylation of heteroarenes (e.g., pyrroles, furans, and thiophenes) in which heteroarylsulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling. These C-H bond functionalizations occurred at the α-position in the case of pyrrole and furan derivatives, while in the case of thiophenes the C-H bonds at the β-position have been heteroarylated. This methodology represents a very simple route to heteroaryl dyads. Moreover, some examples of heteroaryl triads have been synthesized via iterative C-H bond arylations.
- Saoudi, Besma,Debache, Adbelmadjid,Soul, Jean-Franois,Doucet, Henri
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p. 65175 - 65183
(2015/08/18)
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- The pyrolysis of (-)-(S)-nicotine: Racemization and decomposition
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The pyrolytic behaviour of (1)-(S)-nicotine in methanol was investigated using on-line pyrolysis GC/MS to establish whether racemization to the R(+) antipode occurs and to identify other products of pyrolysis. The conditions used included pyrolysing the sample for 15 seconds in an atmosphere of 9% oxygen in nitrogen (275ml/min total flow) across the temperature range of 200°C-1000°C. A chiral Cyclodex-B analytical column (30m × 0.25mm i.d. × 0.25 μm film thickness) was used to separate the enantiomers of nicotine, although the two enantiomer peaks were not baseline resolved. The results of the experiment shows that there is no increase in (+)-(R)-nicotine levels across a wide temperature range. This suggests that the elevated levels of (+)-R-nicotine observed in tobacco smoke (compared to tobacco leaf material) are not due to the pyrolytic auto-racemization of (1)-(S)-nicotine but are a result of more complex interactions between (-)-(S)-nicotine and other smoke components. The pyrolysis of isotopically labelled nicotine established that nicotine undergoes thermal decomposition to β-nicotyrine which in turn may decompose to other products. Chirality 22:442-446, 2010.
- Clayton, Peter,Lu, Annhelen,Bishop, Louise
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experimental part
p. 442 - 446
(2010/08/06)
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- Palladium-catalyzed decarboxylative cross-coupling reaction between heteroaromatic Carboxylic acids and Aryl halides
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"Chemical Equation Presented" A full overview of the decarboxylative cross-coupling reaction between heteroaromatic carboxylic acids and aryl halides is described. This transformation employs palladium catalysts with short reaction times providing facile synthesis of aryl-substituted heteroaromatics. The effect of each reaction parameter including solvent, base, and additive employed as well as the full substrate scope of this transformation are reported. Mechanistic evidence is also disclosed that sheds light on possible reaction pathways.
- Bilodeau, Francois,Brochu, Marie-Christine,Guimond, Nicolas,Thesen, Kris H.,Forgione, Pat
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experimental part
p. 1550 - 1560
(2010/06/12)
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- Nickel or Iron Catalysed Carbon-Carbon Coupling Reaction of Arylenes, Alkenes and Alkines
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Organozinc compounds of the type R1—Ar1—ZnY (1) can be reacted with different functionalized aryl halides R2—Ar2—X (2) in the presence of catalytic amounts of Ni or Fe in a polar solvent or solvent mixture to form polyfunctional biaryles of the type R1—Ar1—Ar2—R2 (3). Organozinc compounds of the type (1) can be represented by the transmetallation reaction of functionalized aryl magnesium halides or lithium aryl compounds with e.g. ZnBr2.
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Page/Page column 7
(2010/08/07)
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- Unexpected intermolecular Pd-catalyzed cross-coupling reaction employing heteroaromatic carboxylic acids as coupling partners
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Aryl-substituted five-membered heteroaromatics have attracted great interest over the past years due to their presence in a large number of pharmaceuticals and natural products. Recently, an advance in the preparation of these scaffolds was achieved by employing a C-H functionalization strategy. This method allows easy access to these biaryl motifs by precluding the necessity of preparing specific coupling partners, although poor regioselectivity is sometimes observed when more than one reactive C-H is present on the substrate. In an effort to circumvent this liability, we envisioned the use of a carboxylic acid moiety as a blocking group that could be later functionalized or removed. Remarkably, the coupling was found to occur exclusively at the position previously occupied by the acid, even in the presence of a reactive C-H group. This selective transformation was also found to proceed with other heteroaromatic carboxylic acids, allowing for the preparation of a variety of aryl-substituted heteroaromatics that would be difficult to obtain via other methods. Copyright
- Forgione, Pat,Brochu, Marie-Christine,St.-Onge, Miguel,Thesen, Kris H.,Bailey, Murray D.,Bilodeau, Francois
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p. 11350 - 11351
(2007/10/03)
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- An efficient Negishi cross-coupling reaction catalyzed by nickel(II) and diethyl phosphite
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A combination of diethyl phosphite-DMAP and Ni(II) salts forms a very effective catalytic system for the cross-coupling reactions of arylzinc halides with aryl, heteroaryl, and alkenyl bromides, chlorides, triflates, and nonaflates. The choice of solvent is quite important and the mixture of THF-N-ethylpyrrolidinone (NEP) (8:1) was found to be optimal. The reaction usually requires only 0.05 mol % of NiCl2 or Ni(acac)2 as catalyst and proceeds at room temperature within 1-48 h.
- Gavryushin, Andrei,Kofink, Christiane,Manolikakes, Georg,Knochel, Paul
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p. 7521 - 7533
(2007/10/03)
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- Efficient cross-coupling of functionalized arylzinc halides catalyzed by a nickel chloride-diethyl phosphite system
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(Chemical Equation Presented) The combination of diethyl phosphite and DMAP as ligands for nickel in an 8:1 THF-N-ethylpyrrolidinone (NEP) mixture allows a very efficient cross-coupling reaction to be performed between various functionalized arylzinc halides and aryl bromides, triflates and activated chlorides. The reaction proceeds at 25°C within 1-48 h and requires only 0.05 mol % of the nickel catalyst.
- Gavryushin, Andrei,Kofink, Christiane,Manolikakes, Georg,Knochel, Paul
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p. 4871 - 4874
(2007/10/03)
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- A new approach to nicotine: Symmetry consideration for synthesis design
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A synthesis of nicotyrine (9), and hence formally racemic nicotine, was carried out by elaboration of the 1:1 adduct 2 of cycloocta-1,5-diene and chlorosulfonyl isocyanate (CISO2-NCO). Transformation of adduct 2 into carbamate 4 was followed by ozonolysis, tosylation, and NaH treatment, which led to pyrrolidinylpiperidinone 6. LiAIH4 Reduction, debenzylation, and aromatization yielded 2.
- Ho, Tse-Lok,Kuzakov, Eugene V.
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p. 2712 - 2716
(2007/10/03)
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- Antibody-catalyzed oxidative degradation of nicotine using riboflavin
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Tobacco abuse remains a major cause of death worldwide despite ample evidence linking nicotine to various disease states. Consequently, immunopharmacotherapeutic approaches for the treatment of nicotine abuse have received increasing attention. Although a number of nicotine-binding antibodies have been disclosed, no antibody catalysts exist which efficiently degrade nicotine into pharmacologically inactive substances. Herein, we report the first catalytic antibodies which can oxidatively degrade nicotine. These biocatalysts use the micronutrient riboflavin and visible light as a source of singlet oxygen for the production of reactive oxygen species. Along with various known nicotine metabolites, antibody-catalyzed nicotine oxidations produce two novel nicotine oxidation products that were also detected in control ozonation reactions of nicotine. The reaction is efficient, with multiple turnovers of catalyst observed and total consumption of nicotine attained. These results demonstrate the potential of harnessing riboflavin as an endogenous sensitizer for antibody-catalyzed oxidations and demonstrate a new approach for the development of an active vaccine for the treatment of nicotine addiction using in vivo catalytically active antibodies.
- Dickerson, Tobin J.,Yamamoto, Noboru,Janda, Kim D.
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p. 4981 - 4987
(2007/10/03)
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- Synthesis of nornicotine, nicotine and other functionalised derivatives using solid-supported reagents and scavengers
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The sequential use of solid-supported reagents and scavengers has led to an efficient synthesis of the natural products nornicotine 1, nicotine 2 and further fuctionalised derivatives. Also reported is a diastereoselective route to both enantiomers of nicotine 2.
- Baxendale, Ian R.,Brusotti, Gloria,Matsuoka, Masato,Ley, Steven V.
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p. 143 - 154
(2007/10/03)
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- Enamine rearrangement of pyridinium salts: Part X - Novel synthesis of indole ring
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β-Nicotyrinium salts (2) undergo ring opening and recyclization reaction when heated with aq. alkyl amine or sodium hydroxide to give indole derivatives (4).
- Etman, H. A.
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p. 285 - 288
(2007/10/02)
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- A New Approach to Functionalized Cyclobutanes: Stereoselective Synthesis of the Enantiomers of Grandisol and Fraganol
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Enantiomerically enriched (+)-grandisol and (+)-fraganol were synthesized using as the key step a new stereoselective synthesis of cyclobutanes fused to γ-lactones by a stereochemically-controlled intramolecular alkylation of α-benzenesulfonyl-γ-lactones.This method provides a way to synthesize the enantiomers in a straightforward manner.
- Martin, Tomas,Rodriguez, Carmen M.,Martin, Victor S.
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p. 1151 - 1164
(2007/10/02)
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- PHOTO-INDUCED ELECTRON-TRANSFER OXIDATION OF NICOTINE
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Irradiation of nicotine in acetonitrile in the presence of TiO2 or 9,10-dicyanoanthracene under oxygen with a 100 W high pressure mercury lamp gave nicotyrine, cotinine,, and dehydronornicotine.A reaction mechanism leading to these products trough nicotine radical cation and superoxide anion is proposed.
- Yamada, Shuzo,Sakai, Toshiaki,Ohashi, Mamoru
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p. 287 - 290
(2007/10/02)
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- PALLADIUM-PHOSPHINE COMPLEX CATALYZED CROSS-COUPLING REACTION OF 1-METHYL-2-PYRROLYL-MAGNESIUM BROMIDE AND -ZINC CHLORIDE WITH ORGANIC HALIDES
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1-Methyl-2-pyrrolyl-magnesium bromide and -zinc chloride, which were prepared from 1-methyl-2-pyrrolyllithium with MgBr2 and ZnCl2 respectively, reacted with aryl- and heteroaromatic halides to give the corresponding 2-substituted pyrroles in good to excellent yields in the presence of palladium-phosphine complexes as catalysts.
- Minato, Akio,Tamao, Kohei,Hayashi, Tamio,Suzuki, Keizo,Kumuda, Makoto
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p. 5319 - 5322
(2007/10/02)
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- Identification of the Product from Nicotine and Sulphur as Bis-1-methyl-2-(3-pyridyl)pyrrol-3-yl Disulphide
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Dithiodinicotyrine, obtained form nicotine and sulphur, has been identified as bis-1-methyl-2-(3-pyridyl)pyrrol-3-yl disulphide (9) from its spectra, reactions, and X-ray crystal structure.Its mode of formation is considered.
- Acheson, R. Morrin,Ferris, Michael J.,Critchley, Stephen R.,Watkin, David J.
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p. 326 - 329
(2007/10/02)
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