- Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO concentration
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We report on the development of a continuous flow process for the palladium catalysed methoxycarbonylation of aryl, heteroaromatic and vinyl iodides and an aryl bromide using a Teflon AF-2400 based Tube-in-Tube reactor to mediate the selective permeation of carbon monoxide into solution at elevated pressures. The low volume of pressurised gas within the reactor (5.6 mL) offers the potential for an enhanced safety profile compared to batch processes. We also present preliminary results for the use of in situ FTIR to measure solution concentrations of carbon monoxide and demonstrate the use of a second reactor to effect the removal of carbon monoxide from the flow stream.
- Koos, Peter,Gross, Ulrike,Polyzos, Anastasios,O'Brien, Matthew,Baxendale, Ian,Ley, Steven V.
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Read Online
- 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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Read Online
- Oxidative Cleavage of Substituted Naphthalenes Induced by Irradiated Semiconductor Powders
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Electron-rich members of a series of substituted naphthalenes react with oxygen to give ring-cleaved products upon long wave ultraviolet irradiation of TiO2 powders suspended in oxygen-saturated acetonitrile solutions of the arene.Reactivity within the series parallels trends in the oxidation potential, i.e., the species with the less positive oxidation potential appears to react more efficiently.A mechanism involving sensitized formation of the substituted naphthalene cation radical is suggested for the semiconductor-mediated photocatalysis.
- Fox, Marye Anne,Chen, Chia-Chung,Younathan, Janet N. N.
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Read Online
- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
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Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
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supporting information
p. 2707 - 2713
(2020/03/30)
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- Capturing Intermediates in the Reaction Catalyzed by NosN, a Class C Radical S-Adenosylmethionine Methylase Involved in the Biosynthesis of the Nosiheptide Side-Ring System
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Nosiheptide is a ribosomally synthesized and post-translationally modified thiopeptide natural product that possesses antibacterial, anticancer, and immunosuppressive properties. It contains a bicyclic structure composed of a large macrocycle and a unique
- Wang, Bo,Lamattina, Joseph W.,Marshall, Savannah L.,Booker, Squire J.
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supporting information
(2019/04/17)
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- Capturing Intermediates in the Reaction Catalyzed by NosN, a Class C Radical S-Adenosylmethionine Methylase Involved in the Biosynthesis of the Nosiheptide Side-Ring System
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Nosiheptide is a ribosomally synthesized and post-translationally modified thiopeptide natural product that possesses antibacterial, anticancer, and immunosuppressive properties. It contains a bicyclic structure composed of a large macrocycle and a unique
- Wang, Bo,Lamattina, Joseph W.,Marshall, Savannah L.,Booker, Squire J.
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supporting information
p. 5788 - 5797
(2019/04/17)
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- Ruthenium-Catalyzed Enantioselective Hydrogenation/Lactonization of 2-Acylarylcarboxylates: Direct Access to Chiral 3-Substituted Phthalides
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Highly enantioselective tandem hydrogenation/lactonization of various 2-acylarylcarboxylates including 2-aroylarylcarboxylates were realized by using [RuCl(benzene)(S)-SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3-substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram-scale reaction was performed to further demonstrate the practicality of this approach.
- Lu, Bin,Zhao, Mengmeng,Ding, Guangni,Xie, Xiaomin,Jiang, Lili,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
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p. 3989 - 3996
(2017/09/13)
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- Synthesis of (R)-3-methylphthalide by reductive cyclization of a 2-acylarylcarboxylate using the chiral boronic ester TarB-H and sodium borohydride
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Background: Phthalides are pervasive benzolactone structural frameworks in nature and have a broad profile of biological activities. Catalytic asymmetric reduction with the in situ lactonization of 2-acylarylcarboxylate compounds is an efficient strategy for chiral phthalide synthesis. The tartaric acid-derived reagent TarB-X is capable of mediating the asymmetric reduction of aromatic ketones using either LiBH4 or NaBH4 as the reductant. Up until now, the asymmetric reduction by Tarb- H/NaBH4 had not been applied to the synthesis of chiral phthalides. Methods: The requsite substrate, methyl 2-acetylbenzoate was obtained by a two step reaction starting from phthalic anhydride and maloninc acid. Tarb-H was obtained by treatment of L-(+)-tartaric acid with phenylboronic acid. The catalyst and NaBH4 were reacted with methyl 2-acetylbenzoate at room temperature for 1 h. The structure of (R)-3-Methylphthalide was established by NMR and mass spectrometry and its enantiomeric excess was determined by HPLC. The relative configuration was deduced by comparison of the optical rotation with data given in the literature. Results: (R)-3-Methylphthalide was obtained in moderte yield and high enantiomeric excess. Conclusion: (R)-3-methylphthalide was prepared in high enantiomeric excesses using an inexpensive and easily synthesized tartaric acid derived boronic ester (TarB-H) with sodium borohydride. The chiral phthalide was obtained in an open flask by reductive cyclization of a 2-acylarylcarboxylate.
- De Souza, Aline Aparecida Nunes,Taylor, Jason Guy
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p. 657 - 660
(2017/01/16)
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- A general continuous flow method for palladium catalysed carbonylation reactions using single and multiple tube-in-tube gas-liquid microreactors
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A series of continuous flow chemistry processes that facilitate the palladium-catalysed carbonylation of aryl and vinyl iodides and aryl bromides with a range of alkoxy, hydroxy and amino nucleophiles is reported. Harnessing a semipermeable Teflon AF-2400 Tube-in-Tube assembly, these reactors permit the controlled transport of carbon monoxide into solution at elevated pressure to generate homogeneous flow streams, avoiding some potential issues associated with segmented flow gas-liquid reactors. As the volume of pressurised gas contained within the device is low, the hazards associated with this are potentially mitigated relative to comparable batch processes. We also show how the incorporation of a second in-line gas-flow reactor allows for the sequential introduction of two gases (carbon monoxide and a gaseous nucleophile) into the reaction stream. A Teflon AF-2400 Tube-in-Tube reactor facilitates the use of carbon monoxide in continuous-flow C-C bond forming reactions providing esters, amides, carboxylic acids, lactones and lactams. Two reactors can be used in series to permit the sequential addition of two reactive gases (CO and Me2NH) into the flow stream.
- Gross, Ulrike,Koos, Peter,O'brien, Matthew,Polyzos, Anastasios,Ley, Steven V.
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supporting information
p. 6418 - 6430
(2016/02/18)
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- Microwave-assisted one-step synthesis of acetophenones via palladium-catalyzed regioselective arylation of vinyloxytrimethylsilane
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The regiochemistry of the palladium-mediated arylation (Heck arylation) of enol ethers is sensitive to the structure of the enol ether, the arylating agent and the catalytic system. In this study, an effective and practical method was successfully developed for the synthesis of acetophenones with high regioselectivity under palladium-catalyzed conditions. A variety of acetophenones was readily prepared from aryl iodides in good to excellent yields under microwave irradiation in a single step. The key feature of our new protocol is the use of vinyloxytrimethylsilane as a highly regioselective acylation reagent. Copyright
- Qian, Wangke,Zhang, Lei,Sun, Haifeng,Jiang, Hualiang,Liu, Hong
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supporting information
p. 3231 - 3236
(2013/01/15)
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- NOVEL IMIDAZOPYRIDINE COMPOUND
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For the prevention and/or treatment of chymase-mediated diseases such as skin diseases, circulatory diseases, digestive system diseases, respiratory diseases, liver diseases, ocular diseases or the like, a drug is provided having as an active ingredient a
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Page/Page column 20
(2012/04/23)
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- The first general and selective palladium(II)-catalyzed alkoxycarbonylation of arylboronates: Interplay among benzoquinone-ligated palladium(0) complex, organoboron, and alcohol solvent
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Methoxycarbonylation of aryl- and alken-ylboron compounds was performed using the palladium (II) acetate/triphenylphosphine [PdACHTUNGTRENNUNG(OAc) 2/PPh3] catalyst with p-benzoquinone as a stoichiometric oxidant in methanol at ambient temperature to obtain the corresponding methyl esters in good yields. A wide variety of functional groups including various carbonyl functionalities, nitrile, nitro, sulfone, and unprotected pyrrole rings were tolerated in the methoxycarbonlation, while the use of higher alcohols except for tert-butanol afforded various pchlorobenzoates in moderate to high yields. The catalytic alkoxycarbonylation proceeded without any acid or base additive, and an oxidative transmetalation step is proposed to explain the exceptional efficacy of this protocol. DFT and MP2 calculations support the proposed mechanism.
- Yamamoto, Yoshihiko
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supporting information; experimental part
p. 478 - 492
(2010/07/03)
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- Benzene compounds
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The present invention provides novel benzene compounds presented by the following formulas, and analogs thereof, that exert an ACC activity-inhibiting effect that is effective in the treatment of obesity, hyperlipemia, fatty liver, hyperglycemia, impaired glucose tolerance, diabetes, diabetic complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy, and diabetic macroangiopathy, hypertension, arteriosclerosis), hypertension, and arteriosclerosis.
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Page/Page column 75-76
(2010/11/27)
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- Synthesis and anticancer activities of novel 1,4-disubstituted phthalazines
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A series of novel 1-anilino-4-(arylsulfanylmethyl)phthalazines were designed and synthesized. The structures of all the compounds were confirmed by IR, 1H-NMR, elemental analysis and MS. The analogues 1-(3-chloro-4-fluoroanilino)-4-(3,4-difluorophenylthio-methyl)phthalazine (12) and 1-(4-fluoro-3-trifluoromethylanilino)-4-(3,4-difluorophenyl-thiomethyl) phthalazine (13) showed higher activity than a cisplatin control when tested in vitro against two different cancer cell lines using the microculture tetrazolium method (MTT) method.
- Li, Juan,Zhao, Yan-Fang,Yuan, Xiao-Ye,Xu, Jing-Xiong,Gong, Ping
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p. 574 - 582
(2007/10/03)
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- Debromination of α-bromoketones and vic-dibromides using indium in the presence of carboxylic acid
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The debromination of α-bromoketones and vic-dibromides using indium metal in the presence of acetic acid at room temperature effectively afforded the corresponding ketones in excellent yield. Copyright Taylor & Francis, Inc.
- Lee, Seung Hwan,Cho, Min Young,Nam, Mi Hye,Park, Young Sang,Yoo, Byung Woo,Lee, Chi-Woo,Yoon, Cheol Min
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p. 1335 - 1341
(2007/10/03)
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- Gas-phase synthesis of hydroxyacetophenones by acylation of phenol with acetic acid
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The gas-phase synthesis of aromatic ketones via acylation of phenol with acetic acid was studied on SiO2-Al2O3, Al-MCM-41, zeolites HY and ZSM5, and tungstophosphoric acid (HPA) supported on MCM-41 and carbon. At contact times of 146 g hr/mole, the initial conversion of phenol varied between 12.5 and 19.1% (HPA/MCM-41), and the initial selectivity to o-hydroxyacetophenone (o-HAP) between 37.1 (HPA/C) and 69.1% (HY). Zeolites HY and ZSM5, which contained strong Bronsted and Lewis acid sites, produced efficiently o-HAP via both the direct C-acylation of phenol and the acylation of phenyl acetate intermediate formed from O-acylation of phenol. On strong Bronsted acid sites of HPA-based catalysts the phenol molecule essentially interacted via the benzene ring, adopting a position parallel to the surface and favoring the attack of acylium ion mainly to the oxygen of phenol.
- Padro,Apesteguia
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p. 308 - 320
(2007/10/03)
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- Palladium-catalyzed synthesis of o-acetylbenzoic acids: A new, efficient general route to 2-hydroxy-3-phenyl-1,4-naphthoquinones and indolo[2,3-b]naphthalene-6,11-diones
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We describe here a new, efficient general synthesis of o-acetylbenzoic acids by Heck palladium-catalyzed arylation of n-butyl vinyl ether with o-bromobenzoic acid esters and the use of these compounds as starting materials for the synthesis of 3-benzylideneisochroman-1,4-diones, which readily rearrange to 2-hydroxy-3-phenyl-1,4-naphthoquinones. The application of this strategy to the synthesis of indolo[2,3-b]naphthalene-6,11-diones is also described.
- Barcia, José C,Cruces, Jacobo,Estévez, Juan C,Estévez, Ramón J,Castedo, Luis
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p. 5141 - 5144
(2007/10/03)
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- Preparation and cycloaddition reactions of novel heterocyclic mesomeric betaines
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The heterocyclic mesomeric betaines 6a-c reacted with dimethyl acetylenedicarboxylate and ethyl propiolate giving the 1,3-dipolar cycloaddition products 7a-c and 8a-c, respectively. With esters of maleic, fumaric, acrylic and methacrylic acids, mesomeric betaines 6a and 6b gave substituted tetralone derivatives. (C) 2000 Elsevier Science Ltd.
- Morgan, David O.,David Ollis,Stanforth, Stephen P.
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p. 5523 - 5534
(2007/10/03)
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- Lanthanide triflate catalysed reactions of acetals with primary amines and cascade cyclisation reactions
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The formation of imines from acetals and primary amines can be carried out at significantly lower temperatures using scandium or lanthanide triflates as catalysts, than in the absence of a catalyst: the intermediate aminol ethers can also take part in cascade cyclisation reactions, for example using tryptamine and ethyl tryptophanate.
- Heaney, Harry,Simcox, Michael T.,Slawin, Alexandra M.Z.,Giles, Robert G.
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p. 640 - 642
(2007/10/03)
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- A new synthetic route to isoquinolin-1(2H)-one derivatives from 3-hydroxyphthalides
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A new synthetic route for the conversion of substituted 3-hydroxyphthalides into the corresponding isoquinolin-1(2H)-one was established. This method can be applied to the preparation of isoquinolin-1(2H)-ones with electron-withdrawing groups that are relatively difficult to synthesize by conventional procedures.
- Sugimoto,Shinba-Tanaka,Ishikawa
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p. 431 - 434
(2007/10/02)
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- α-Regioselectivity in Palladium-Catalyzed Arylation of Acyclic Enol Ethers
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Regioselective α-arylation of acyclic enol ethers by aryl trifluoromethanesulfonates, aryl bromide, aryl iodides, and aroyl chlorides is described.The outcome of the reaction proved to be dependent from the relationship between ligand and counterion in the oxidative complex.
- Cabri, Walter,Candiani, Ilaria,Bedeschi, Angelo,Penco, Sergio,Santi, Roberto
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p. 1481 - 1486
(2007/10/02)
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- PALLADIUM-CATALYZED α-ARYLATION OF VINYL BUTYL ETHER WITH ARYL HALIDES
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The reaction between vinyl butyl ether and either aryl or aroyl halides in the presence of the catalytic system Pd(OAc)2/DPPP is described.High selectivity toward the α-arylated product is obtained with the addition of TlOAc.
- Cabri, Walter,Candiani, Ilaria,Bedeschi, Angelo,Santi, Roberto
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p. 1753 - 1756
(2007/10/02)
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- THE METHYLATION OF CARBOXYLIC ACIDS USING METHYL TRICHLOROACETATE
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Metyl trichloroacetate has been shown to methylate carboxylic acids with the loss of chloroform and carbon dioxide.
- Renga, James M.,Wang, Pen-Chung
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- Palladium-Catalyzed Acylation of Unsaturated Halides by Anions of Enol Ethers
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Zinc salts of enol ether anions are coupled to aryl and alkenyl halides by using palladium catalysts, effecting a direct acetylation of aryl and alkenyl halides.Zinc salts of allenic ethers are coupled with aryl and alkenyl halides under similar conditions to give α,β-unsaturated ketones, the allenic ether serving as a source of the acryloyl group.Allenic ethers were γ arylated in a palladium-catalyzed coupling with aryl halides to give β,β-diaryl-α,β-unsaturated aldehydes.
- Russell, Charles E.,Hegedus, Louis S.
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p. 943 - 949
(2007/10/02)
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- Deactivation of Triplet Phenyl Alkyl Ketones by Conjugatively Electron-Withdrawing Substituents
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Para-cyano, -carbomethoxy, and -acyl substituents decrease the triplet reactivity of valerophenone (γ-hydrogen abstraction), whereas comparable meta substituents increase reactivity.Spectroscopic results are presented which indicate that para-(-R) substituents lower ?,?* triplet energies so much more than n,?* energies that the lowest triplets become largely ?,?* in nature.Meta-(-R) substituents do not stabilize ?,?* triplets enough to invert triplet levels.Both substitution patterns support a largely 1,4-biradical structure for the lowest ?,?* triplet of acylbenzenes.Ortho substituents show the usual steric anomalies: ortho cyano enhances valerophenone triplet reactivity by stabilizing the n,?* triplet; ortho carbomethoxy deactivates valerophenone by stabilizing the ?,?* triplet but not the n,?.*
- Wagner, Peter J.,Siebert, Elizabeth J.
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p. 7329 - 7335
(2007/10/02)
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