- Zinc-Catalyzed Asymmetric Hydrosilylation of Cyclic Imines: Synthesis of Chiral 2-Aryl-Substituted Pyrrolidines as Pharmaceutical Building Blocks
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The first successful enantioselective hydrosilylation of cyclic imines promoted by a chiral zinc complex is reported. In situ generated zinc-ProPhenol complex with silane afforded pharmaceutically relevant enantioenriched 2-aryl-substituted pyrrolidines in high yields and with excellent enantioselectivities (up to 99% ee). The synthetic utility of presented methodology is demonstrated in an efficient synthesis of the corresponding chiral cyclic amines, being pharmaceutical drug precursors to the Aticaprant and Larotrectinib. (Figure presented.).
- W?glarz, Izabela,Michalak, Karol,Mlynarski, Jacek
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supporting information
p. 1317 - 1321
(2020/12/09)
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- Benzylic Hydroperoxidation via Visible-Light-Induced Csp3-H Activation
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A highly efficient benzylic hydroperoxidation has been realized through a visible-light-induced Csp3-H activation. We believe that this reaction undergoes a direct HAT mechanism catalyzed by eosin Y. This approach features the use of a metal-free catalyst (eosin Y), an energy-economical light source (blue LED), and a sustainable oxidant (molecular oxygen). Primary, secondary, and tertiary hydroperoxides as well as silyl, benzyl, and acyl peroxides were successfully prepared with good yields and excellent functional group compatibility.
- Inoa, Joan,Patel, Mansi,Dominici, Grecia,Eldabagh, Reem,Patel, Anjali,Lee, John,Xing, Yalan
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p. 6181 - 6187
(2020/05/22)
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- Generalized Chemoselective Transfer Hydrogenation/Hydrodeuteration
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A generalized, simple and efficient transfer hydrogenation of unsaturated bonds has been developed using HBPin and various proton reagents as hydrogen sources. The substrates, including alkenes, alkynes, aromatic heterocycles, aldehydes, ketones, imines, azo, nitro, epoxy and nitrile compounds, are all applied to this catalytic system. Various groups, which cannot survive under the Pd/C/H2 combination, are tolerated. The activity of the reactants was studied and the trends are as follows: styrene'diphenylmethanimine'benzaldehyde'azobenzene'nitrobenzene'quinoline'acetophenone'benzonitrile. Substrates bearing two or more different unsaturated bonds were also investigated and transfer hydrogenation occurred with excellent chemoselectivity. Nano-palladium catalyst in situ generated from Pd(OAc)2 and HBPin extremely improved the TH efficiency. Furthermore, chemoselective anti-Markovnikov hydrodeuteration of terminal aromatic olefins was achieved using D2O and HBPin via in situ HD generation and discrimination. (Figure presented.).
- Wang, Yong,Cao, Xinyi,Zhao, Leyao,Pi, Chao,Ji, Jingfei,Cui, Xiuling,Wu, Yangjie
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supporting information
p. 4119 - 4129
(2020/08/10)
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- Selective aerobic oxidation of alkyl aromatics on Bi2MoO6 nanoplates decorated with Pt nanoparticles under visible light irradiation
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Pt/Bi2MoO6 nanoplates are efficient photocatalysts for the selective oxidation of saturated C-H bonds in alkyl aromatics under visible light illumination using O2 as an oxidant. This study opens a new window for direct C-H functionalization through the photocatalytic method based on cheap Bi2MoO6 semiconductor materials.
- Zhang, Bao,Yang, Xiaojing,Li, Jun,Cheng, Gang
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supporting information
p. 12194 - 12197
(2018/11/21)
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- Conformations, equilibrium thermodynamics and rotational barriers of secondary thiobenzanilides
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The article deals with conformational behaviour of 2-methoxy-2′-hydroxythiobenzanilides. The CS-NH group of these compounds preferentially adopts the Z-conformation. Entropy favours the Z-conformer over the E-conformer, whereas enthalpy slightly favours the E-conformer over the Z-conformer. The rotational barrier about the CS-NH bond was determined to be (81.5±0.4) kJ/mol. No significant rotational barrier was found on the Ar-CS and Ar-NH bonds. All experimental outcomes are compared with the results of quantum-chemical calculations.
- Kozic, Ján,Novák, Zdeněk,?ímal, Václav,Profant, Václav,Kune?, Ji?í,Vin?ová, Jarmila
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p. 2072 - 2083
(2016/04/09)
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- Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors
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Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this P1 binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.
- Wurtz, Nicholas R.,Parkhurst, Brandon L.,Jiang, Wen,DeLucca, Indawati,Zhang, Xiaojun,Ladziata, Vladimir,Cheney, Daniel L.,Bozarth, Jeffrey R.,Rendina, Alan R.,Wei, Anzhi,Luettgen, Joseph M.,Wu, Yiming,Wong, Pancras C.,Seiffert, Dietmar A.,Wexler, Ruth R.,Priestley, E. Scott
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supporting information
p. 1077 - 1081
(2016/12/18)
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- Transition metal free intramolecular selective oxidative C(sp3)-N coupling: Synthesis of N-aryl-isoindolinones from 2-alkylbenzamides
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A synthetic method has been developed for the preparation of biologically important isoindolinones including indoprofen and DWP205190 drugs from 2-alkylbenzamide substrates by transition metal-free intramolecular selective oxidative coupling of C(sp3)-H and N-H bonds utilizing iodine, potassium carbonate and di-tert-butyl peroxide in acetonitrile at 110-140 °C.
- Verma, Ajay,Patel, Saket,Meenakshi,Kumar, Amit,Yadav, Abhimanyu,Kumar, Shailesh,Jana, Sadhan,Sharma, Shubham,Prasad, Ch. Durga,Kumar, Sangit
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supporting information
p. 1371 - 1374
(2015/02/18)
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- Iodoarene-Catalyzed Stereospecific Intramolecular sp3 C-H Amination: Reaction Development and Mechanistic Insights
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A new strategy is reported for intramolecular sp3 C-H amination under mild reaction conditions using iodoarene as catalyst and m-CPBA as oxidant. This C-H functionalization involving iodine(III) reagents generated in situ occurs readily at sterically hindered tertiary C-H bonds. DFT (M06-2X) calculations show that the preferred pathway involves an iodonium cation intermediate and proceeds via an energetically concerted transition state, through hydride transfer followed by the spontaneous C-N bond formation. This leads to the experimentally observed amination at a chiral center without loss of stereochemical information.
- Zhu, Chendan,Liang, Yong,Hong, Xin,Sun, Heqing,Sun, Wei-Yin,Houk,Shi, Zhuangzhi
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supporting information
p. 7564 - 7567
(2015/06/30)
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- Inclusion complex containing epoxy resin composition for semiconductor encapsulation
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The invention is an epoxy resin composition for sealing a semiconductor, including (A) an epoxy resin and (B) a clathrate complex. The clathrate complex is one of (b1) an aromatic carboxylic acid compound, and (b2) at least one imidazole compound represented by formula (II): wherein R2 represents a hydrogen atom, C1-C10 alkyl group, phenyl group, benzyl group or cyanoethyl group, and R3 to R5 represent a hydrogen atom, nitro group, halogen atom, C1-C20 alkyl group, phenyl group, benzyl group, hydroxymethyl group or C1-C20 acyl group. The composition has improved storage stability, retains flowability when sealing, and achieves an effective curing rate applicable for sealing delicate semiconductors.
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- Lipase-mediated resolution of substituted 2-aryl-propanols: Application to the enantioselective synthesis of phenolic sesquiterpenes
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A comprehensive study of the lipase-mediated resolution of substituted 2-aryl-propanols is reported. The latter alcohols were submitted to the irreversible acetylation catalyzed either by PPL, CRL, or lipase PS. The enantioselectivity of these transformations was dependent on the type of lipase used. The type of substituents and particularly their position on the aromatic ring strongly affected the selectivity of the reaction. The experiments described prove that PPL is the more versatile lipase catalyzing the acetylation with an enantiomeric ratio (E) value that ranges from 1 up to 144, depending on the substrate used. Conversely, the same transformations were catalyzed by CRL and lipase PS with an enantiomeric ratio value, which is always less than 5. The remarkable behavior of PPL was exploited in the large scale resolution of some substituted 2-aryl-propanols whose enantiomeric forms are relevant building blocks in the enantioselective synthesis of phenolic sesquiterpenes. By these means, the synthesis of (S)-turmeronol B and the formal syntheses of (R)-curcumene, (R)-curcuphenol, (R)-xanthorrhizol, and (R)-curcuhydroquinone were accomplished.
- Serra, Stefano
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experimental part
p. 619 - 628
(2011/07/08)
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- Direct carboxylation of arenes and halobenzenes with CO2 by the combined use of AlBr3 and R3SiCl
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The Lewis acid-mediated direct carboxylation of aromatic compounds with CO2 is efficiently promoted by the addition of silyl chlorides bearing three alkyl and/or aryl substituents in total on the silicon atom. Thus, toluene, xylenes, mesitylene, and some other alkylbenzenes are treated with a 1:1 mixture of AlBr3 and Ph3SiCl in neat substrates under CO2 pressure (3.0 MPa) at room temperature, to give the corresponding carboxylic acids in 60-97% yields, based on AlBr3. Polycyclic arenes, including naphthalene, phenanthrene, and biphenyl, are regioselectively carboxylated in 91-98% yields with the aid of 1 molar equiv of AlBr3 and Ph3SiCl in an appropriate solvent, chosen from benzene, chlorobenzene, and fluorobenzene. These solvents, as well as bromobenzene, resist carboxylation; however, they are also carboxylated in moderate yields when treated with a 1:5 mixture of AlBr3 and iPrSiCl at elevated temperatures. The FT-IR spectrum of a mixture prepared by exposing a suspension of AlBr3 and Ph3SiCl in cyclohexane to CO 2 exhibits an absorption band around 1650 cm-1, assigned to the C=O stretching vibration of a species consisting of CO2, AlBr3, and Ph3SiCl, which suggests that the silyl chlorides activate CO2 in cooperation with AlBr3. 1H NMR analysis of unworked-up reaction mixtures reveals that the products merge as aluminum carboxylates. The mass balance concerning silicon indicates that the silyl chlorides are recycled during the reaction sequence. On the basis of these observations, a feasible mechanism is proposed for the present carboxylation.
- Nemoto, Koji,Yoshida, Hiroki,Egusa, Naoki,Morohashi, Naoya,Hattori, Tetsutaro
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experimental part
p. 7855 - 7862
(2011/02/21)
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- Direct B-alkyl Suzuki-Miyaura cross-coupling of trialkyl-boranes with aryl bromides in the presence of unmasked acidic or basic functions and base-labile protections under mild non-aqueous conditions
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An efficient and chemoselective palladium-catalyzed direct B-alkyl Suzuki-Miyaura cross-coupling of trialkylboranes with diversely functionalized aryl bromides is described. A wide variety of unmasked acidic or basic functions are tolerated. The mild non-
- Wang, Bing,Sun, Hui-Xia,Sun, Zhi-Hua,Lin, Guo-Qiang
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experimental part
p. 415 - 422
(2009/10/23)
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- Substituent effects on the base-catalysed hydrolysis of phenyl esters of ortho-substituted benzoic acids
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Fourteen model phenyl esters of 2-substituted benzoic acids were synthesised. Structures and purity of model compounds were confirmed by 1H and 13C NMR spectroscopy, as well as by HPLC and elemental analysis. Kinetics of base-catalysed hydrolysis of model phenyl esters occurring by the BAC2 mechanism were measured by UV spectrophotometry in 50% (v/v) aqueous dimethyl sulfoxide solutions at 25 °C under pseudo-first-order reaction conditions (c(NaOH) = 0.001-1.0 mol 1-1). Linear relation between JE- and log kobs with the slope close to unity was found for all model compounds. Neither one-parameter nor multiparameter Hammett-type description of variability of experimental data obtained for phenyl esters of 2-substituted benzoic acids was found. Two groups (conjugating and non-conjugating) were created by division of ortho-substituents in ortho-position using the AISE theory, based on their interaction with the reaction centre.
- Bauerova, Ingrid,Ludwig, Miroslav
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p. 770 - 784
(2007/10/03)
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- Dialkylhydrazides for directed orthometalations
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Dimethylhydrazides are shown to be excellent substrates for the directed orthometalation reaction. The advantage of using the hydrazide is that it is easily removed by treatment with H5IO6 or CuCl2 to give the carboxylic acid under very mild conditions, in contrast to other amides that generally require harshly acidic conditions to achieve hydrolysis. (C) 2000 Elsevier Science Ltd.
- Pratt, Scott A.,Goble, Michael P.,Mulvaney, Michael J.,Wuts, Peter G. M.
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p. 3559 - 3562
(2007/10/03)
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- Protoberberins from Reissert Compounds VI [1]. Diastereoselective Synthesis and Relative Configuration of 2-Benzoyl-1-cyano-1-(1-phenylalkyl)-1,2-dihydroisoquinolines
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The alkylation of Reissert compounds 8 by sec-benzyl bromides 4, 7, and 10 diastereoselectively affords the title compounds 11 and 12. X-Ray structure analysis confirms an opposite configuration of the chiral centers in 11 and 12. The benzyl bromides 4, 7, and 10 are prepared by standard procedures.
- Reimann, Eberhard,Erdle, Wolfgang,Weigl, Claudia,Polborn, Kurt
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p. 313 - 326
(2007/10/03)
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- Microbial asymmetric syntheses of 3-alkylphthalide derivatives
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Phthalide derivatives, almost all of which have an S-configuration, have a wide range of activity and exist in Angerica sinensis Diels and Sligusticum wallichiii Franch. For the first time, optically active (S)-3-methylphthalide derivatives were synthesized using two methods, asymmetric microbial reduction and microbial hydroxylation. For the first method, methyl 2-acetylbenzoate was synthesized as a substrate, which was reduced asymmetrically by Geotrichum candidum IFO 34614 to obtain (S)-3-methylphtalide in 92% yield (99% enantiomeric excess, ee). For the second method, 2-ethylbenzoic acid was employed as a substrate which was hydroxylated asymmetrically at the benzylic position by either Pseudomonas putida ATCC 12633 or Aspergillus niger IFO 6661, whose fermentation was induced by o-toluic acid, to obtain (S)-3-methylphthalide in 80% yield (99% ee). (S)-3-Butylphthalide and (S)-3-octylphthalide were obtained in the same manner in 12% yield (ee = 99%) and 10% yield (ee = 99%), respectively.
- Kitayama, Takashi
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p. 3765 - 3774
(2007/10/03)
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- The Reactions of Carbene Intermediates from the Reaction of Trialkyl Phosphites with Dialkyl Benzoylphosphonates: Intramolecular Cyclisations of 2-Substituted Dialkyl Benzoylphosphonates
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The reaction of dialkyl aroylphosphonates 1 with trialkyl phosphites leads to the formation of carbene intermediates 3 via the anionic intermediates 2.The carbene intermediates 3 (R = 2-Me, 2-Prn, 2-Bun, 2-MeS, 2-EtO and 2-EtS) have
- Griffiths, D. Vaughan,Griffiths, Penelope A.,Karim, Khalku,Whitehead, Belinda J.
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p. 901 - 925
(2007/10/03)
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- Novel Quasiphosphonium Ylides from the Reaction of Trialkyl Phosphites with Dialkyl Benzoylphosphonates: Evidence for Carbene Intermediates in the Intramolecular Cyclisation of 2-Substituted Dialkyl Benzoylphosphonates
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The reaction of dialkyl aroylphosphonates 1 with trialkyl phosphites leads to the formation of novel quasiphosphonium ylides 4 which in some cases thermally rearrange to the bisphosphonates 5. 2-Substituted dialkyl aroylphosphonates may also undergo intra
- Griffiths, D. Vaughan,Griffiths, Penelope A.,Whitehead, Belinda J.,Tebby, John C.
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p. 479 - 484
(2007/10/02)
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- Photocyclization of -(o-Tolyl)acetophenones: Triplet and 1,5-biradical reactivity
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Several ring-substituted α-(o-tolyl)acetophenones undergo photocyclization to 2-indanol derivatives in high quantum efficiency in solution and in high chemical yield as solids. The mechanism for reaction involves triplet state δ-hydrogen atom abstraction that generates 1,5-biradicals. Quenching studies indicate that the n.π* excited triplets of these ketones react, with rate constants >108 s-1. Variations in triplet reactivity are ascribed to conformational equilibria that populate reactive and unreactive geometries to different extents. The α-aryl ring eclipses the carbonyl in the lowest energy geometry, from which the most favorable geometry for reaction can be reached by small bond rotations. α-(2,4,6-Triisopropylpheny)acetophenone forms the relatively long lived enol as well as indanol in solvent-dependent ratios; deuterium labeling indicates that the 1,5-biradical disproportionates to form enol. This does not happen with α-mesitylacetophenone, so its 54% cyclization quantum efficiency is ascribed to an internal triplet quenching that competes with hydrogen abstraction. This internal quenching is presumed to be of the charge-transfer type and does not appear to lead directly to 1,5-biradicals. 1-Methyl-2-phenyl-2-indanol is formed from α-(o-ethylpheny)acetophenone with a Z/E ratio of 20:1 in benzene and 2:1 in methanol. The 1,5-biradical intermediates were characterized by flash spectroscopy; they have lifetimes between 15 and 45 ns, with those derived from α-(o-isopropylphenyl) ketones being twice as long-lived as those derived from α-(o-methylphenyl) ketones, and show only a small solvent dependence. Biradical lifetimes and the diastereoselectivity of cyclization are interpreted in terms of biradical intersystem crossing occurring preferentially along the reaction coordinate for cyclization, such that the two processes effectively occur concurrently. The applicability of this concept to other biradicals is discussed.
- Wagner, Peter J.,Meador, Michael A.,Zhou, Boli,Park, Bong-Ser
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p. 9630 - 9639
(2007/10/02)
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- Asymmetric syntheses of 1,6-dialkyl-1,4-cyclohexadiene derivatives
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Ortho-lithiation-alkylation of tertiary benzamide 3 provides a series of 2-substituted chiral benzatnides 3a-g (Scheme I). Birch reduction of 3a-j followed by alkylation of the resulting chiral amide enolate with Mel at -78 °C gives 1,6-di-alkyl-1,4-cyclohexadiene derivatives 4a-j with excellent diastereoselectivities (Table I). Applications of this asymmetric synthesis are illustrated by conversions of 4g to enantiomerically pure bicyclic lactone 9 and octalone 11 (Scheme III) and 4j to hexahydro-9-anthracenone 14 (Scheme IV).
- Schultz, Arthur G.,Green, Neal J.
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p. 4931 - 4936
(2007/10/02)
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- Tobacco smoke chemistry 3. Aromatic acids of cigarette smoke condensate.
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A fraction containing mainly aromatic acids has been isolated from cigarette smoke condensate. Gas chromatographic and mass spectral analysis of the corresponding methyl esters and comparison with reference compounds, many of which were synthesized for this purpose, made possible the identification of 27 constituents (Table 1). Eighteen of these have not been detected in tobacco smoke condensate before.
- Arnarp,Dahlin,Enzell,Pettersson
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p. 381 - 385
(2007/10/02)
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- On the Generation and Characterization of the Spirooctadienyl Anion in the Gas Phase
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Three routes have been explored in both a high-pressure chemical ionization (CI) source and a low-pressure Fourier transform ion cyclotron resonance (FT-ICR) cell to generate the spirooctadienyl anion in the gas phase: (i) proton abstraction from spiroocta-4,6-diene; (ii) expulsion of trimethylsilyl fluoride by phenyl ring participation following fluoride anion attack upon the silicon centre of 2-phenylethyl trimethylsilane; and (iii) collisionally induced dissociation (CID) of the carboxylate anion of 3-phenylpropanoic acid via carbon dioxide loss.From comparison of the CID spectra of various reference (1-) ions with those of the (1-) ions with those of the (1-) ions which could be generated via the routes (i) and (iii) in the CI source it can be concluded that only the third route yields a (1-) in whose CID spectrum is not inconsistent with the one expected for the spirooctadienyl anion.In the FT-ICR cell (1-) ions are generated along all three routes; their structures have been identified by specific ion-molecule reactions and appear to be different.Route (i) yields an α-methyl benzyl anion, probably due to isomerization within the ion-molecule complex formed.An ortho-ethylphenyl anions is formed along route (ii), presumably due to an intramolecular ortho proton abstraction in the generated trimethylsilyl fluoride solvated 2-phenylethyl primary carbanion.The (1-) ion formed along route (iii) shows reactions similar to those of the 1,1-dimethylcyclohexadienyl anion which is structurally related to the spirooctadienyl anion.Furthermore, the (1-) ion generated via route (iii) reacts with hexafluorobenzene under expulsion of only one hydrogen fluoride molecule which contains exclusively one of the original phenyl ring hydrogen atoms.On the basis of all these observations it is therefore quite likely that the spirooctadienyl anion is formed by collisionally induced decarboxylation of the 3-phenylpropanoic acid carboxylate anion and can be a long-lived and stable species in the gas phase.
- Maas, Wilfrid P. M.,Veelen, Peter A. van,Nibbering, Nico M. M.
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p. 546 - 558
(2007/10/02)
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- Reaction of O-Silylated Enolates of Carboxylic Esters with Benzyne. A Convenient Route to ortho-Alkylbenzoic Acids
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The reaction of O-silylated enolates of carboxylic esters with benzyne proceeds smoothly to afford ortho-alkylbenzoic acids in moderate yields.
- Ali, Syed Masarrat,Tanimoto, Shigeo
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p. 1465 - 1466
(2007/10/02)
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- OXIDATIVE COUPLING THE TOLUIC ACID DIANION SYSTEM
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The behavior of all three toluic acid isomers upon treatment with two equivalents of base followed by the addition of iodide-containing reagents is described.
- Belletire, J. L.,Spletzer, E. G.
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p. 575 - 584
(2007/10/02)
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- SYNTHESIS OF ISOCOUMARINS VIA THALLATION-OLEFINATION OF BENZOIC ACIDS
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Benzoic acid and substituted benzoic acids are readily thallated by thallium(III) trifluoroacetate and subsequently reacted with palladium chloride and simple olefins, allylic halides, vinyl halides, or vinyl esters to give isocoumarins.The organic halide reactions are catalytic in palladium. 1,2- and 1,3-dienes also react catalytically to afford 4-alkylidene- and 3-vinyl-3,4-dihydroisocoumarins, respectively.Vinylcyclopropanes also afford 3-vinyl-3,4-dihydroisocoumarins.This highly convenient thallation-olefination approach appears quite general for the synthesis of isocoumarins.
- Larock, R. C.,Varaprath, S.,Lau, H. H.,Fellows, C. A.
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p. 5274 - 5284
(2007/10/02)
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