- Ground-State Electron Transfer as an Initiation Mechanism for Biocatalytic C-C Bond Forming Reactions
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The development of non-natural reaction mechanisms is an attractive strategy for expanding the synthetic capabilities of substrate promiscuous enzymes. Here, we report an "ene"-reductase catalyzed asymmetric hydroalkylation of olefins using α-bromoketones as radical precursors. Radical initiation occurs via ground-state electron transfer from the flavin cofactor located within the enzyme active site, an underrepresented mechanism in flavin biocatalysis. Four rounds of site saturation mutagenesis were used to access a variant of the "ene"-reductase nicotinamide-dependent cyclohexanone reductase (NCR) from Zymomonas mobiles capable of catalyzing a cyclization to furnish β-chiral cyclopentanones with high levels of enantioselectivity. Additionally, wild-type NCR can catalyze intermolecular couplings with precise stereochemical control over the radical termination step. This report highlights the utility for ground-state electron transfers to enable non-natural biocatalytic C-C bond forming reactions.
- Fu, Haigen,Lam, Heather,Emmanuel, Megan A.,Kim, Ji Hye,Sandoval, Braddock A.,Hyster, Todd K.
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p. 9622 - 9629
(2021/07/01)
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- The synthesis method of one-carbon ring expansion of cycloketone dericatives from β-selenyl cycloketone dericatives
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The present invention relates to a method for preparing a cyclic ketone derivative with an increased carbon number by performing a ring expansion reaction of a β-selenyl cyclic ketone derivative. The present invention was first developed by performing the
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Paragraph 0041; 0044-0048; 0098-0102
(2020/09/08)
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- Electrochemical Radical Selenylation/1,2-Carbon Migration and Dowd-Beckwith-Type Ring-Expansion Sequences of Alkenylcyclobutanols
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Electrochemical oxidative radical selenylation/1,2-carbon migration and Dowd-Beckwith-type ring-expansion sequences of alkenylcyclobutanols were developed in this study. This approach is environmentally benign and uses shelf-stable diselenides as selenium
- Kim, Yeon Joo,Kim, Dae Young
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p. 1021 - 1025
(2019/02/14)
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- Cobalt-Catalyzed Regioselective Olefin Isomerization under Kinetic Control
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Olefin isomerization is a significant transformation in organic synthesis, which provides a convenient synthetic route for internal olefins and remote functionalization processes. The selectivity of an olefin isomerization process is often thermodynamically controlled. Thus, to achieve selectivity under kinetic control is very challenging. Herein, we report a novel cobalt-catalyzed regioselective olefin isomerization reaction. By taking the advantage of fine-tunable NNP-pincer ligand structures, this catalytic system features high kinetic control of regioselectivity. This mild catalytic system enables the isomerization of 1,1-disubstituted olefins bearing a wide range of functional groups in excellent yields and regioselectivity. The synthetic utility of this transformation was highlighted by the highly selective preparation of a key intermediate for the total synthesis of minfiensine. Moreover, a new strategy was developed to realize the selective monoisomerization of 1-alkenes to 2-alkenes dictated by installing substituents on the γ-position of the double bonds. Mechanistic studies supported that the in situ generated Co-H species underwent migratory insertion of double bond/β-H elimination sequence to afford the isomerization product. The less hindered olefin products were always preferred in this cobalt-catalyzed olefin isomerization due to an effective ligand control of the regioselectivity for the β-H elimination step.
- Liu, Xufang,Zhang, Wei,Wang, Yujie,Zhang, Ze-Xin,Jiao, Lei,Liu, Qiang
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supporting information
p. 6873 - 6882
(2018/05/30)
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- Isoquinolone compound and application thereof
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The invention relates to an isoquinolone compound and application thereof. The invention in particular relates to an isoquinolone compound used as a HIF prolyl hydroxylase inhibitor (HIF-PHI) and a pharmaceutical composition thereof. Moreover, the present invention provides the application of the isoquinolinone compound or the pharmaceutical composition thereof in the preparation of a medicament for preventing or treating HIF-associated or HIF-mediated diseases as anemia or ischemia, local ischemia or hypoxia.
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Paragraph 0998-1000
(2018/09/08)
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- Photocatalytic Radical Alkylation of Electrophilic Olefins by Benzylic and Alkylic Zinc-Sulfinates
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Alkyl radicals are obtained by photocatalytic oxidation of readily prepared or commercially available zinc sulfinates. The convenient benzylation and alkylation of a variety of electron-poor olefins triggered by the iridium(III) complex 6 Ir[dF(CF3)ppy]2(dtbbpy)PF6 as photocatalyst is described. Moreover, it is shown that zinc sulfinates can be used for facile nonradical sulfonylation reactions with highly electrophilic Michael acceptors.
- Gualandi, Andrea,Mazzarella, Daniele,Ortega-Martínez, Aitor,Mengozzi, Luca,Calcinelli, Fabio,Matteucci, Elia,Monti, Filippo,Armaroli, Nicola,Sambri, Letizia,Cozzi, Pier Giorgio
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p. 5357 - 5362
(2017/08/17)
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- Carbonyls as Latent Alkyl Carbanions for Conjugate Additions
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Conjugate addition of carbon nucleophiles to electron-deficient olefins is one of the most powerful methods for forming carbon–carbon bonds. Despite great achievements in controlling the selectivity, variation of the carbon nucleophiles remains largely underexplored, with this approach relying mostly on organometallic reagents. Herein, we report that naturally abundant carbonyls can act as latent carbon nucleophiles for conjugate additions through a ruthenium-catalyzed process, with water and nitrogen as innocuous byproducts. The key to our success is homogeneous ruthenium(II) catalysis, combined with phosphines as spectator ligands and hydrazine as the reducing agent. This chemistry allows the incorporation of highly functionalized alkyl fragments into a vast array of electron-deficient olefins under mild reaction conditions in a reaction complementary to the classical organometallic-reagent-based conjugate additions mediated or catalyzed by “soft” transition metals.
- Dai, Xi-Jie,Wang, Haining,Li, Chao-Jun
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supporting information
p. 6302 - 6306
(2017/05/19)
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- Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones and related compounds
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Novel benzylation reagents BnR2MgLi were obtained by mixing benzylmagnesium chloride (BnMgCl) and appropriate organolithium compounds (RLi). As BnR2MgLi complexes are more nucleophilic than the parent Grignard compound they enabled regioselective C6-addition to electrophilic N-substituted 2-(thio)-pyridones and C4-addition to poorly reactive NH 2-(thio)pyridones in high and good yields, respectively. Thus, the application of these new reagents in efficient synthesis of 6-benzyl-3,6-dihydro- and 4-benzyl-3,4-dihydropyridin-2(1H)-ones is described. The prospect of wider application of BnR2MgLi in 1,4-addition to other electrophiles, comprising six-membered α,β-unsaturated systems is also presented.
- So?nicki, Jacek G.,Idzik, Tomasz,Borzyszkowska, Aleksandra,Wróblewski, Emil,Maciejewska, Gabriela,Struk, ?ukasz
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p. 481 - 493
(2017/01/13)
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- Origin of the E/Z Selectivity in the Synthesis of Tetrasubstituted Olefins by Wittig Reaction of α-Fluorophosphonium Ylides: An Explanation for the Low Stereoselectivity Observed in Reactions of α-Alkoxy Aldehydes
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A series of tetrasubstituted fluoroalkenes were synthesized in good yield and high E/Z selectivity (up to 96/4) by Wittig reaction between α-heterosubstituted ketones and α-fluorophosphonium ylides. A detailed study of factors that control stereoselectivity in these reactions shows that stereoselectivity is the result of stabilizing CH···F and N···C=O interactions in the addition TS leading to the E isomer. This analysis provides a rationale for the observed decrease in selectivity for reactions of stabilized ylides with α-alkoxy aldehydes.
- Depré, Dominique,Vermeulen, Wim A. A.,Lang, Yolande,Dubois, Jean,Vandevivere, Jan,Vandermeersch, Jeremy,Huang, Longchuan,Robiette, Rapha?l
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supporting information
p. 1414 - 1417
(2017/03/23)
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- Sunlight-driven trifluoromethylation of olefinic substrates by photoredox catalysis: A green organic process
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The principles and utility of photoredox catalysis in organic synthesis are described. After a brief description of the features of the two types of catalytic photoredox processes following the reductive quenching cycle (RQC) and the oxidative quenching cycle (OQC), the discussion is focused on organic transformations based on OQC, in particular the trifluoromethylation of olefinic substrates with electrophilic trifluoromethylating reagents furnishing solvolytic addition products and substitution products. It is concluded that catalytic photoredox systems are green from the point of view of harmfulness, safety, and energy source (visible light, including sunlight). Future prospects of photoredox catalysis will be also discussed.
- Akita, Munetaka,Koike, Takashi
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p. 742 - 751
(2015/07/15)
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- Catalytic enantioselective conjugate addition of Grignard reagents to cyclic enones using C1-1,1′-bisisoquinoline-based chiral ligands
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New highly constrained chiral C1-1,1′-bisisoquinoline ligands were examined in the enantioselective conjugate addition of Grignard reagents to cyclohexenone and cyclopentenone. The desired 1,4-adducts were obtained in excellent yield and moderate enantiomeric excess (up to 35%). Copyright Taylor & Francis Group, LLC.
- Qi, Gao,Judeh, Zaher M.A.
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experimental part
p. 1585 - 1592
(2012/05/04)
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- Demonstration of promoted zinc schlenk equilibria, their equilibrium values and derived reactivity
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The presence of promoted Schlenk equilibria for organozinc halide species has been explicitly demonstrated by 13CNMR studies. Thus, addition of methylaluminoxane (McAlO)n, MAO, to RZnX (R = Et, Bn, ArCH 2, (CH2)
- Blake, Alexander J.,Shannon, Jonathan,Stephens, John C.,Woodward, Simon
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p. 2462 - 2472
(2008/04/01)
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- Free radical-promoted conjugate addition of activated bromo compounds using titanocene(III) chloride as the radical initiator
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Free radical-promoted conjugate addition of activated bromo compounds to α,β-unsaturated ketones and reactive α,β-unsaturated esters has been described using titanocene(III) chloride (Cp2TiCl) as the radical initiator. Cp2TiCl was prepared in situ from commercially available Cp2TiCl2 and activated zinc dust in THF.
- Mandal, Samir Kumar,Jana, Samaraesh,Roy, Subhas Chandra
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p. 6115 - 6117
(2007/10/03)
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- Reductive free-radical alkylations and cyclisations mediated by 1-alkylcyclohexa-2,5-diene-1-carboxylic acids
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A range of 1-alkylcyclohexa-2,5-diene-1-carboxylic acids were prepared by Birch reduction-alkylation of benzoic acid and their efficiency as mediators of alkyl radical chain addition and cyclisation processes was investigated. Reductive alkylations were respectably successful, even with only one or two equivalents of alkene, for secondary, tertiary and benzylic radicals. Reaction of 1-[2-(cyclohex-2-enyloxy)ethyl]cyclohexa-2,5-diene-1-carboxylic acid yielded the product of exo-trig-cyclisation, i.e. 7-oxabicyclo[4.3.0]nonane, in a yield comparable to that obtained from the tributyltin hydride induced cyclisation of 3-(2′-iodoethoxy)-cyclohexene. This, together with the isolation of both exo- and endo-cyclisation products from 1-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-ylmethoxy)ethyl]cyclohexa-2,5-diene- 1-carboxylic acid established that ring closures could also be satisfactorily mediated with these reagents. Preparations were completely free of metal contaminants and direct reduction of the alkyl radicals, prior to addition or cyclisation, was completely absent. However, the desired products were accompanied by alkylbenzenes, together with by-products from the initiator decompositions, and this complicated work-up. Failure to obtain 1-[2-(prop-2-yn-1-yloxy)cyclohexyl]cyclohexa-2,5-diene-1-carboxylic acid in Birch reductive alkylations with trans-1-iodo-2-(prop-2-yn-1-yloxy)cyclohexane (and the corresponding bromide) indicated a limitation on precursor synthesis. The Birch reduction-alkylation was not of universal applicability and was suppressed for alkyl halides having β-substituents.
- Baguley, Paul A.,Walton, John C.
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p. 2073 - 2082
(2007/10/03)
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- Beryllium dichloride: Efficient promoter for the addition of organolithiums and organomagnesiums to cyclohexen-2-one
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Organoberyllium compounds, generated by transmetallation from Grignard and organolithium reagents react with 2-cyclohexenone to give predominantly the adducts resulting from conjugated addition. The chemoselectivity of this reaction was found to be highly dependent upon the nature of organic moiety and of the conditions used.
- Krief, Alain,De Vos, Marie Joelle,De Lombart, Stephane,Bosret, Jean,Couty, Francois
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p. 6295 - 6298
(2007/10/03)
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- Allylbarium reagents: Unprecedented regio- and stereoselective allylation reactions of carbonyl compounds
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The first direct preparation of allylbarium reagents by reaction of in situ generated reactive barium with various allylic chlorides and their new and unexpected selective allylation reactions with carbonyl compounds are disclosed. Highly reactive barium was readily prepared by the reduction of barium iodide with 2 equiv of lithium biphenylide in dry THF at room temperature. A variety of carbonyl compounds reacted with barium reagents generated from (E)- or (Z)-allylic chlorides in THF at -78 °C. All reactions resulted in high yields with remarkable α-selectivities not only with aldehydes but also with ketones. The double bond geometry of the starting allylic chloride was completely retained in each case. Stereochemically homogeneous (E)- and (Z)-β,γ-unsaturated carboxylic acids were easily prepared in good yields by highly α-selective carboxylation of allylic barium reagents with carbon dioxide. A selective Michael addition reaction with α,β-unsaturated cycloalkanone was also achieved using an allylbarium reagent. Treatment of 2-cyclopentenone (1 equiv) with allylbarium chloride (2 equiv) in THF at -78 °C for 20 min afforded 3-allylcyclopentanone in 94% yield with a 1,4/1,2 ratio of >99/1. Furthermore, the in situ generated barium enolate was efficiently trapped with various kinds of electrophiles (Me2C=CHCH2Br, nC5H11CHO, and CH3COCl).
- Yanagisawa, Akira,Habaue, Shigeki,Yasue, Katsutaka,Yamamoto, Hisashi
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p. 6130 - 6141
(2007/10/02)
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- CONJUGATE ADDITION OF BENZYL COPPER REAGENTS TO α,β-ENOATES AND -ENONES.
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Several benzylic copper reagents, BnCu(CN)MgCl, Bn2CuMgCl, BnCu-TMSCl-HMPA, and BnCu-TMSCl-TMEDA, facilitate the conjugate addition of the benzyl ligand to α,b-enones, but only BnCu-TMSCl-TMEDA gave high yields with α,β-unsaturated esters.
- Heerden, Pieter S. van,Bezuidenhoudt, Barend C. B.,Steenkamp, Jacobus A.,Ferreira, Daneel
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p. 2383 - 2386
(2007/10/02)
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- A NOVEL SYNTHESIS OF KETOPROFEN, IMPORTANT NON-STEROIDAL ANTIINFLAMMATORY AGENT
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The α-propionic acid moiety in ketoprofen is attached through Wittig Horner reaction of ethylphosphono propionate on 3-benzyl cyclohexanone, prepared by G. reaction of benzylmagnesium chloride with 2-cyclohexenone (in presence of cuprous chloride).
- Mitra, R. B.,Joshi, Vijaya S.
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p. 2259 - 2266
(2007/10/02)
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- Ultrasound in Organic Synthesis. 7. Preparation of Organozinc Reagents and Their Nickel-Catalyzed Reactions with α,β-Unsaturated Carbonyl Compounds
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Diorganozinc compounds can be prepared with great ease and efficiency in a one-pot process, by sonication of lithium, an organic halide, and a zinc halide in THF or toluene mixtures.The reagents thus obtained give rise to clean and selective conjugate additions to α,β-unsaturated aldehydes and ketones in the presence of catalytic amounts of nickel acetylacetonate.
- Petrier, Christian,Barbosa, Jayne C. de Souza,Dupuy, Claude,Luche, Jean-Louis
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p. 5761 - 5765
(2007/10/02)
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- NOVEL SYNTHESIS OF BENZYLLITHIUMS FROM BENZYLSELENIDES
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Benzylselenides are found to be valuable precursors of benzyllithiums.The scope of the new method is disclosed.
- Clarembeau, M.,Krief, A.
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p. 1093 - 1096
(2007/10/02)
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- FLUORIDE ION INDUCED REACTIONS OF OREGANOSILANES WITH SATURATED LACTONES AND αβ-ENONES
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Benzyl-, heteroaryl-, and allylsilanes, under the catalytic action of CsF or silica/TBAF, react in mild conditions with electrophiles such as δ-valero and ε-caprolactone, and with cyclohexen-2-one.
- Ricci, Alfredo,Fiorenza, Mariella,Grifagni, M. Antonietta,Bartolini, Giuseppe,Seconi, Giancarlo
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p. 5079 - 5082
(2007/10/02)
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