- Access to Chiral Polycyclic 1,4-Dihydropyridines via Organocatalytic Formal [3 + 3] Annulation of 2-(1-Alkynyl)-2-alken-1-ones with 3-Aminobenzofurans
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A rational designed tandem reaction of 2-(1-alkynyl)-2-alken-1-ones with 3-aminobenzofurans enabled by a chiral bifunctional catalyst is described, affording biologically significant polycyclic 1,4-dihydropyridines in moderate to good yields (43-82%) with good to excellent enantioselectivities (83-99%). This formal [3 + 3] annulation reaction reveals good practicality when conducted on a gram scale, and the cycloadduct has the capability for further elaborations.
- Li, Zhanhuan,Zhou, Hongwei,Xu, Jianfeng
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- Combined Computational and Experimental Studies on the Asymmetric Michael Addition of α-Aminomaleimides to β-Nitrostyrenes Using an Organocatalyst Derived from Cinchona Alkaloid
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Maleimides are often used as electrophiles in conventional reactions; however, their application as nucleophiles is limited to only a few reactions, and reactions utilizing α-aminomaleimides as asymmetric Michael donors have not been reported to date. Thus, in this work, asymmetric Michael addition of α-aminomaleimides as Michael donors to β-nitrostyrenes was conducted for the first time using an organocatalyst derived from a Cinchona alkaloid. Density functional theory investigations were crucial to improve the enantioselectivity of the adduct.
- Sakai, Naoki,Kawashima, Kyohei,Kajitani, Masashi,Mori, Seiji,Oriyama, Takeshi
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p. 5714 - 5718
(2021/08/01)
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- Asymmetric Cycloetherification by Bifunctional Organocatalyst
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Attempts to obtain enantiomerically enriched tetrahydrofuran derivatives via an intramolecular oxy -Michael addition reaction of ?-hydroxyenone is discussed. Despite previous difficulties associated with the asymmetric induction of this reaction, which can proceed even without a catalyst, a highly efficient asymmetric induction was realized using a bifunctional organocatalyst derived from a cinchona alkaloid. The reaction could be extended to ζ-hydroxyenone to yield an optically active tetrahydropyran derivative with a high ee. In these reactions, it is important for the gentle acidic and basic sites in the bifunctional organocatalyst to be arranged properly within the molecular skeleton of the catalyst. The high performance asymmetric induction relied on the affinity of the catalyst for the substrate, which played an important role. A disubstituted tetrahydropyran synthesis could be effectively performed via kinetic resolution using ζ-hydroxyenone containing a secondary alcohol moiety using a chiral phosphoric acid catalyst.
- Asano, Keisuke,Matsubara, Seijiro
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p. 4243 - 4253
(2018/07/03)
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- Highly enantioselective aza-henry reaction of ketimines catalyzed by a chiral bifunctional thiourea-tertiary amine derived from quinine
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We have developed a highly enantioselective aza-Henry reaction of aryl α-ketoester-derived N-Ts ketimines with a wide range of substrate scope by a simpler bifunctional thiourea-tertiary amine catalyst derived from quinine. A variety of ketimines were investigated and corresponding products were obtained in excellent yields (up to 99% yield) with excellent enatioselectivities (up to 99% ee).
- Fang, Yanhong,Lu, Ning,Wei, Zhonglin,Cao, Jungang,Liang, Dapeng,Lin, Yingjie,Duan, Haifeng
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supporting information
p. 4371 - 4375
(2018/11/25)
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- Intramolecular Chirality Transfer [2 + 2] Cycloadditions of Allenoates and Alkenes
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Intramolecular chirality transfer [2 + 2] cycloaddition of enantiomerically enriched allenoates and alkenes is presented. The use of a chiral catalyst was found to be critical to achieve high levels of diastereoselectivity compared to use of an achiral catalyst. The method developed leads to highly substituted cyclobutanes that would be difficult to prepare by alternative methods.
- Xu, Yao,Hong, Young J.,Tantillo, Dean J.,Brown, M. Kevin
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p. 3703 - 3706
(2017/07/26)
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- Synthesis of ent-[3]-Ladderanol: Development and Application of Intramolecular Chirality Transfer [2+2] Cycloadditions of Allenic Ketones and Alkenes
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An enantioselective synthesis of ent-[3]-ladderanol is presented. The ladderanes are an interesting class of molecules for their unique structure of fused cyclobutane rings as well as their perceived biological function of organism protection. The route h
- Line, Nathan J.,Witherspoon, Brittany P.,Hancock, Erin N.,Brown, M. Kevin
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p. 14392 - 14395
(2017/10/24)
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- Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids
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The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations.
- Del Pozo, Sandra,Vera, Silvia,Oiarbide, Mikel,Palomo, Claudio
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p. 15308 - 15311
(2017/11/06)
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- ASYMMETRIC SYNTHESIS OF FUNAPIDE
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This invention is directed to asymmetric synthesis of funapide, which is useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.
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- Solvent-free enantioselective conjugate addition and bioactivities of nitromethane to Chalcone containing pyridine
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A series of chiral thioureas derived from quinine were tested as catalysts in the enantioselective Michael additions of nitromethane to α,β-unsaturated ketones containing pyridine. The best results were obtained with the bifunctional catalyst prepared from 3,5-di(trifluoromethyl)-aniline under solvent-free conditions. This thiourea promoted the reaction with high enantioselectivities and chemical yields for aryl ketones. The origins of enantioselectivity were further investigated via experiment and computation. Meanwhile, the products from our reaction showed potent antibacterial activities against rice bacterial leaf blight, with the S-enantiomer performing much better than the R-enantiomer. Given the promising bioactivity of this class of molecules, our work is expected to offer important applications in developing future generations for drug design.
- Zhang, Guoping,Zhu, Chun,Liu, Dengyue,Pan, Jianke,Zhang, Jian,Hu, Deyu,Song, Baoan
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p. 129 - 136
(2016/12/23)
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- Stereoselective glycosylation of 2-nitrogalactals catalyzed by a bifunctional organocatalyst
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The use of a bifunctional cinchona/thiourea organocatalyst for the direct and α-stereoselective glycosylation of 2-nitrogalactals is demonstrated for the first time. The conditions are mild, practical, and applicable to a wide range of glycoside acceptors with products being isolated in good to excellent yields. The method is exemplified in the synthesis of mucin type Core 6 and 7 glycopeptides.
- Medina, Sandra,Harper, Matthew J.,Balmond, Edward I.,Miranda, Silvia,Crisenza, Giacomo E. M.,Coe, Diane M.,McGarrigle, Eoghan M.,Galan, M. Carmen
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p. 4222 - 4225
(2016/09/09)
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- Stereoselective reaction of 2-carboxythioesters-1,3-dithiane with nitroalkenes: An organocatalytic strategy for the asymmetric addition of a glyoxylate anion equivalent
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An efficient organocatalytic methodology has been developed to perform the stereoselective addition of 2-carboxythioesters-1,3-dithiane to nitroalkenes. Under mild reaction conditions γ-nitro-β-aryl-α-keto esters with up to 92% ee were obtained, realizing a formal catalytic stereoselective conjugate addition of the glyoxylate anion synthon. The reaction products are versatile starting materials for further synthetic transformations; for example, the simultaneous reduction of the nitro group and removal of the dithiane ring was accomplished, allowing the preparation of a GABAB receptor agonist baclofen.
- Massolo, Elisabetta,Benaglia, Maurizio,Genoni, Andrea,Annunziata, Rita,Celentano, Giuseppe,Gaggero, Nicoletta
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p. 5591 - 5596
(2015/05/27)
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- From meso-Lactide to Isotactic Polylactide: Epimerization by B/N Lewis Pairs and Kinetic Resolution by Organic Catalysts
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B/N Lewis pairs have been discovered to catalyze rapid epimerization of meso-lactide (LA) or LA diastereomers quantitatively into rac-LA. The obtained rac-LA is kinetically polymerized into poly(l-lactide) and optically resolved d-LA, with a high stereoselectivity kL/kD of 53 and an ee of 91% at 50.6% monomer conversion, by newly designed bifunctional chiral catalyst 4 that incorporates three key elements (β-isocupreidine core, thiourea functionality, and chiral BINAM) into a single organic molecule. The epimerization and enantioselective polymerization can be coupled into a one-pot process for transforming meso-LA directly into poly(l-lactide) and d-LA.
- Zhu, Jian-Bo,Chen, Eugene Y.-X.
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p. 12506 - 12509
(2015/10/19)
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- Procedure-controlled enantioselectivity switch in organocatalytic 2-oxazolidinone synthesis
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In a novel organocatalytic formal [3 + 2] cycloaddition to afford chiral 2-oxazolidinones, an enantioselectivity switch could be induced by changing the manner of addition of the reactants, even when the reaction components (cinchona-alkaloid-derived aminothiourea catalyst, substrates, and solvent) were the same.
- Fukata, Yukihiro,Asano, Keisuke,Matsubara, Seijiro
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p. 12160 - 12163
(2013/09/23)
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- Enantioselective sulfonation of enones with sulfonyl imines by cooperative N-heterocyclic-carbene/thiourea/tertiary-amine multicatalysis
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Many hands make light work: In an organocatalytic asymmetric sulfonation of enones, the activation of a sulfonyl imine by an N-heterocyclic carbene (NHC) catalyst led to the release of a sulfinic anion, which underwent nucleophilic addition to the enone. The enantioselectivity of the process was controlled by a chiral thiourea/amine co-catalyst through anion recognition and hydrogen-bonding interactions. Tol=p-tolyl. Copyright
- Jin, Zhichao,Xu, Jianfeng,Yang, Song,Song, Bao-An,Chi, Yonggui Robin
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supporting information
p. 12354 - 12358
(2013/12/04)
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- Catalytic asymmetric direct vinylogous michael addition of deconjugated butenolides to maleimides for the construction of quaternary stereogenic centers
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Competition under control: A practical and efficient direct asymmetric vinylogous Michael reaction of deconjugated butenolides has been developed (see scheme). The products of this reaction, highly functionalized chiral succinimides, are obtained in excel
- Manna, Madhu Sudan,Mukherjee, Santanu
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p. 15277 - 15282
(2013/01/15)
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- Asymmetric catalytic cycloetherification mediated by bifunctional organocatalysts
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Oxacyclic structures such as tetrahydrofuran (THF) rings are commonly found in many bioactive compounds, and this has led to several efforts toward their stereoselective syntheses. However, the process of catalytic asymmetric cycloetherification for their straightforward synthesis has remained a challenge. In this study, we demonstrate a novel asymmetric synthesis method for THF via the catalytic cycloetherification of ε-hydroxy-α,β- unsaturated ketones mediated by cinchona-alkaloid-thiourea-based bifunctional organocatalysts. This catalytic process represents a highly practical cycloetherification method that provides excellent enantioselectivities, even with low catalyst loadings at ambient temperature.
- Asano, Keisuke,Matsubara, Seijiro
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p. 16711 - 16713
(2011/12/03)
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- Organocatalytic enantioselective Michael addition of β-diketones to β-nitrostyrene: The first Michael addition of dipivaloylmethane to an activated olefin
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The addition of a family of β-diketones to β-nitrostyrene was explored using a library of cinchona organocatalysts. A thiourea organocatalyst, under improved reaction conditions, is shown to be much more efficient at catalyzing this reaction than previously reported giving excellent yields and enantioselectivites (up to 95% yield and 97% ee). The same thiourea organocatalyst was employed in the first successful Michael addition of the sterically challenging dipivaloylmethane to β-nitrostyrene (99% ee). ARKAT-USA, Inc.
- Gavin, Declan P.,Stephens, John C.
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experimental part
p. 407 - 421
(2011/08/07)
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- Physical organic study of structure-activity-enantioselectivity relationships in asymmetric bifunctional thiourea catalysis: Hints for the design of new organocatalysts
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The first pKa scales for chiral thiourea catalysts and their correlations with the corresponding parameters of the bifunctional catalysis was reported. Twenty chiral thiourea-tertiary amine compounds were synthesized and electronic variations w
- Li, Xin,Deng, Hui,Zhang, Bo,Li, Jiuyuan,Zhang, Long,Luo, Sanzhong,Cheng, Jin-Pei
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supporting information; experimental part
p. 450 - 455
(2010/06/22)
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