- Catalytic α-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation
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This study reports the catalytic deracemization of ketones bearing stereocenters in the α-position in a single reaction via deprotonation, followed by enantioselective protonation. The principle of microscopic reversibility, which has previously rendered this strategy elusive, is overcome by a photoredox deprotonation through single electron transfer and subsequent hydrogen atom transfer (HAT). Specifically, the irradiation of racemic pyridylketones in the presence of a single photocatalyst and a tertiary amine provides nonracemic carbonyl compounds with up to 97% enantiomeric excess. The photocatalyst harvests the visible light, induces the redox process, and is responsible for the asymmetric induction, while the amine serves as a single electron donor, HAT reagent, and proton source. This conceptually simple light-driven strategy of coupling a photoredox deprotonation with a stereocontrolled protonation, in conjunction with an enrichment process, serves as a blueprint for other deracemizations of ubiquitous carbonyl compounds.
- Chen, Shuming,Gao, Anthony Z.,Ivlev, Sergei I.,Meggers, Eric,Nie, Xin,Ye, Chen-Xi,Zhang, Chenhao
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supporting information
p. 13393 - 13400
(2021/09/03)
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- Iron-Catalyzed Asymmetric Decarboxylative Azidation
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The first iron-catalyzed asymmetric azidation of benzylic peresters has been reported with trimethylsilyl azide (TMSN3) as the azido source. Hydrocarbon radicals that lack of strong interactions were capable to be enantioselectively azidated. The reaction features good functional group tolerance, high yields, and mild conditions. The chiral benzylic azides can further be used in click reaction, phosphoramidation, and reductive amination, which demonstrate the synthetic values of this reaction.
- Wang, Kaikai,Li, Yajun,Li, Xiaoyan,Li, Daliang,Bao, Hongli
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supporting information
p. 8847 - 8851
(2021/11/24)
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- Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
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AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
- Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
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p. 5956 - 5971
(2020/06/05)
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- Reducing versus basic properties of 1,2-diaryl-1,2-disodioethanes
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The outcome of the reaction between halogenated arylacetic acids and 1,2-diaryl-1,2-disodioethanes strongly depends on the nature of both reaction partners, and it can be rationalized in terms of a competition between reducing and basic properties of the vic-diorganometals, as well as of the ease of the reductive cleavage of the different carbon-halide bonds. As an application of these findings, we developed a particularly mild approach to the synthesis of halogenated and non halogenated α-substituted arylacetic acids.
- Azzena, Ugo,Dettori, Giovanna,Pisano, Luisa,Pittalis, Mario
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experimental part
p. 3470 - 3475
(2011/06/17)
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- Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries
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A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable.
- Stivala, Craig E.,Zakarian, Armen
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supporting information; experimental part
p. 11936 - 11939
(2011/09/19)
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- Synthesis of 3,3-and 4,4-alkyl-phenyl-substituted pyrrolidin-2-one derivatives
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Syntheses of 3,3-and 4,4-alkyl-phenyl-substituted pyrrolidin-2-one derivatives are described. The final compounds were obtained by the reductive cyclization of relevant cyanoalkanoate esters using NaBH4 and CoCl2.6H2O. The obtained pyrroIidin-2-one derivatives are pharmacophoric fragments for the synthesis of various biologically active compounds.
- Kulig,Ignasik,Malawska
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experimental part
p. 1629 - 1636
(2010/07/06)
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- Unexpected formation of 3,3a,4,7a-tetrahydrobenzofuran-2,5-dione as well as arene carboxylic acids upon formal double exo nucleophilic addition of R1R2C-COO- to anisolechromium tricarbonyl complexes
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Bis(trimethylsily)ketene acetals of the general structure 2 (R1 = H,Me,R2 = Me,Et,Pr(i),CMe = CH2) react at -78°C in the presence of Bu(t)OK with a series of arenechromium tricarbonyl complexes 3 to give as expected, after oxidation with I2 followed by silica gel chromatography, arylcarboxylic acids 7. In the case of anisolechromium tricarbonyl 8, besides the m-methoxyarylcarboxylic acids, tetrahydrobenzofuran-2,5-diones 11, are formed as the result of a double nucleophilic addition.
- Bellassoued, Moncef,Chelain, Evelyne,Collot, Jerome,Rudler, Henri,Vaissermann, Jacqueline
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p. 187 - 188
(2007/10/03)
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- Generation of nitroalkanes, hydroximoyl halides and nitrile oxides from the reactions of β-nitrostyrenes with Grignard or organolithium reagents
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The β-nitrostyrenes 1 or 2 react with Grignard or organolithium reagents in ether or THF solution to generate by 1,4-addition the intermediate nitronates A. When A is treated with dilute hydrochloric acid, high yields of the nitroalkanes 3 (and oximes 4) or 5 are obtained Hydroximoyl halides 6, 8 or nitrile oxides 7 can be isolated when the intermediate A is slowly added to the ice cold concentrated hydrohalic acid. The same products 6 and/or 7 are observed if the nitronates, generated from the substrate 1a, are added to 85% aqueous H2SO4 but only the hydrolyzed carboxylic acids 9 are generated when the β-nitrostyrenes 2 are reacted with Grignard reagents and worked up under the same condition. The nitrile oxides 7 can undergo 1,3-dipolar cycloaddition with alkenes or alkynes to generate 2-isoxazolines or isoxazoles. A one-pot synthesis of the [n,3,0] bicyclic (n = 3 or 4) compounds 23-27 by intramolecular nitrile oxide-olefin cycloadditions is reported.
- Yao, Ching-Fa,Kao, Kuo-Hsi,Liu, Ju-Tsung,Chu, Cheng-Ming,Wang, Yeh,Chen, Wen-Chang,Lin, Yu-Mei,Lin, Wen-Wei,Yan, Ming-Chung,Liu, Jing-Yuan,Chuang, Ming-Ching,Shiue, Jin-Lien
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p. 791 - 822
(2007/10/03)
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- Reactions of β-nitrostyrenes with Grignard reagents
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α-Phenyl-β-nitrostyrene 1a and β-nitrostyrene 1b react with Grignard reagents to generate hydroxyimoyl halides 3 or nitrile oxides 4 after workup with ice cold concentrated aqueous HX acid solution. Carboxylic acids 5 are the only products isolated from 1b and products 3 or 4 are still obtained from 1a when concentrated sulfuric acid solution is used.
- Yao, Ching-Fa,Chen, Wen-Chang,Lin, Yu-Mei
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p. 6339 - 6342
(2007/10/03)
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- RENIN INHIBITING COMPOUNDS
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Compounds which are amino acid derivatives and have the formula STR1 in which R 1 is hydrogen or methyl, R 2 is ethyl, propyl or imidazol-4-yl, R 3 is isobutyl, cyclohexylmethyl or benzyl, and A is defined as herein are useful as renin inhibitors.
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- Hydration Reactivity of Persistent Conjugated Ketenes
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The acid, neutral, and base hydrations of the crowded alkenylketene 1 and the arylketenes i-PrCPh=C=O (2) and t-BuCPh=C=O (3) have been measured, together with solvent isotope effects and general acid catalysis of the hydration of 1.The arylketenes 2 and 3 are the first for which acid-catalyzed hydration has been demonstrated.These ketenes show significantly lower reactivity than simple ketenes, and this is interpreted as the result of both steric and electronic factors operating in mechanisms involving rate-limiting proton transfer to carbon (the γ-carbon in 1) for the acid-catalyzed reaction, while both the neutral and hydroxide-induced reactions involve rate-limiting nucleophilic attack in the plane of the ketene on the carbonyl carbon.
- Allen, Annette D.,Stevenson, Andrew,Tidwell, Thomas T.
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p. 2843 - 2848
(2007/10/02)
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- 2-Methyl-1-phenyl-1-propenyllithium. A Vinyllithium Derivative Showing Catalyzed Transmetalation
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Full preparative and kinetic details are given for the apparent vinyl-to-allyl anion rearrangement of the title compound 1.The rapid and quantitative formation of the allyllithium derivative 7 is shown to be catalyzed by 2-methyl-1-phenyl-1-propene (2).An intermolecular transmetalation mechanism with de-aggregation and ionization steps is suggested to explain the orders of reaction, parameters of activation, and solvent dependency.
- Knorr, Rudolf,Lattke, Ernst
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p. 2116 - 2131
(2007/10/02)
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- Process for preparing phenyl-acetic acid esters
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A process for preparing a substituted phenyl-acetic acid ester of the formula (I), SPC1 wherein R1 is an ethyl group or an isopropyl group, R2 is a hydrogen atom, a C1 -C4 alkyl group, a methoxy group, a halogen atom or a methylenedioxy group, which comprises reacting a quaternary ammonium salt of the formula (III), SPC2 wherein X is a halogen atom, and A is an alkylamine, pyridine or an N-alkylaniline, with a carboxylic acid of the formula (II), SPC3 wherein R1 and R2 are each as defined above, its reactive derivative, or a mixture of the acid and its reactive derivative.
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