- Chemo- and Regioselective Asymmetric Friedel-Crafts Reaction of Furans and Thiophenes with α,β-Unsaturated Aldehydes through Dual Activation
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A highly chemo- and regioselective Friedel-Crafts alkylation reaction of furans and thiophenes has been developed, which relies on the activation from the remote conjugated Mukaiyama silyl enol ether motif. Excellent enantioslectivity is generally obtained in reactions with α,β-unsaturated aldehydes under the well-established iminium ion catalysis of a chiral secondary amine.
- Zhang, Xiao-Ru,Zhou, Su-Lan,Yuan, Yi,Du, Wei,Chen, Ying-Chun
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- Ring-Opening Reactions of Thiophene Derivatives by the Use of the Birch Reduction
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It was found that the Birch reduction of 2-(2-thienyl)alkanoic acid and subsequent alkylation with benzyl bromide resulted in the formation of 2-alkyl-3-benzylthio-3-hexenoic acid selectively.Further, the Birch reduction of a 2,3-dialkylthiophene and subsequent alkylation with benzyl bromide gave a tetrasubstituted olefin which was formed by a selective C-S bond fission between the 1 and 5 positions of the thiophene nuclei.In contrast to these results, the Birch reduction of 3-thiophenecarboxylic acid derivatives and subsequent benzylation gave 2-alkyl-4-benzylthio-3-butenoic acid which was formed by a C-S bond fission between the 1 and 2 positions of the thiophene nuclei.
- Kumamoto, Takanobu,Hosoya, Kumiko,Kanzaki, Satoshi,Masuko, Kazuhiro,Watanabe, Mikio,Shirai, Kozo
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- Markovnikov Wacker-Tsuji Oxidation of Allyl(hetero)arenes and Application in a One-Pot Photo-Metal-Biocatalytic Approach to Enantioenriched Amines and Alcohols
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The Wacker-Tsuji aerobic oxidation of various allyl(hetero)arenes under photocatalytic conditions to form the corresponding methyl ketones is presented. By using a palladium complex [PdCl2(MeCN)2] and the photosensitizer [Acr-Mes]ClO4 in aqueous medium and at room temperature, and by simple irradiation with blue led light, the desired carbonyl compounds were synthesized with high conversions (>80%) and excellent selectivities (>90%). The key process was the transient formation of Pd nanoparticles that can activate oxygen, thus recycling the Pd(II) species necessary in the Wacker oxidative reaction. While light irradiation was strictly mandatory, the addition of the photocatalyst improved the reaction selectivity, due to the formation of the starting allyl(hetero)arene from some of the obtained by-products, thus entering back in the Wacker-Tsuji catalytic cycle. Once optimized, the oxidation reaction was combined in a one-pot two-step sequential protocol with an enzymatic transformation. Depending on the biocatalyst employed, i. e. an amine transaminase or an alcohol dehydrogenase, the corresponding (R)- and (S)-1-arylpropan-2-amines or 1-arylpropan-2-ols, respectively, could be synthesized in most cases with high yields (>70%) and in enantiopure form. Finally, an application of this photo-metal-biocatalytic strategy has been demonstrated in order to get access in a straightforward manner to selegiline, an anti-Parkinson drug. (Figure presented.).
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
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supporting information
p. 4096 - 4108
(2021/08/19)
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- Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding
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An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5-tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5-tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition. As such, the studies represent an example of not just an enhancement in the rate or efficiency of a heterocyclic azadiene cycloaddition by hydrogen bonding catalysis but also the first to alter the mode (N1/N4 vs C3/C6) of cycloaddition.
- Zhu, Zixi,Glinkerman, Christopher M.,Boger, Dale L.
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p. 20778 - 20787
(2020/12/22)
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- SUMO INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds and compositions capable of acting as inhibitors of small ubiquitin-like modifier (SUMO) family of proteins. The compounds and compositions may be used in the treatment of cancer. There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.
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Paragraph 0174
(2020/10/09)
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- Palladium-Catalyzed Intramolecular Cyclization of Nitroalkenes: Synthesis of Thienopyrroles
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In the presence of carbon monoxide, the palladium/phenanthroline system catalyzes the intramolecular amination of thiophene rings following the reduction of a nitroalkene moiety directly attached to the S-heterocyclic ring. Optimization of the ligand and reaction conditions allowed the synthesis of a series of thienopyrroles aryl/alkyl-substituted at either the 2- or 3-position of the pyrrole ring. By using low pressures of carbon monoxide (5 bars), high yields of fused bicyclic compounds have been obtained (up to 98 % yield).
- El-Atawy, Mohamed A.,Ferretti, Francesco,Ragaini, Fabio
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p. 1902 - 1910
(2017/04/21)
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- Chemoselective Continuous Ru-Catalyzed Hydrogen-Transfer Oppenauer-Type Oxidation of Secondary Alcohols
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A continuous flow method for the selective oxidation of secondary alcohols is reported. The method is based on an Oppenauer-type ruthenium-catalyzed hydrogen-transfer process that uses acetone as both solvent and oxidant. The process utilizes a low loading (1 mol%) of the commercially available ruthenium catalyst [Ru(p-cymene)Cl2]2 and triethylamine as a base and can be successfully applied to a range of different substrates, with a good level of functional group tolerance.
- Labes, Ricardo,Battilocchio, Claudio,Mateos, Carlos,Cumming, Graham R.,De Frutos, Oscar,Rincón, Juan A.,Binder, Kellie,Ley, Steven V.
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supporting information
p. 1419 - 1422
(2017/09/23)
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- Remote enantioselective friedel-crafts alkylations of furans through HOMO activation
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Catalytic asymmetric Friedel-Crafts alkylation is a powerful protocol for constructing a chiral C(sp2)-C(sp3) bond. Most previous examples rely on LUMO activation of the electrophiles using chiral catalysts with subsequent attack by electron-rich arenes. Presented herein is an alternative strategy in which the HOMO of the aromatic π system of 2-furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine. Exclusive regioselective alkylation at the 5-position occurred with alkylidenemalononitriles, and high reactivity and excellent enantioselectivity (up to 95 % ee) was obtained by this remote activation. Alternative strategy: An asymmetric and regioselective Friedel-Crafts alkylation reaction of 2-furfuryl ketones and alkylidenemalononitriles was developed and involves the in situ generation of a formal HOMO-raised trienamine species. A diversity of alkylation products were produced in moderate to excellent enantioselectivity under the catalysis of a chiral bifunctional primary amine-thiourea (1).
- Li, Jun-Long,Yue, Cai-Zhen,Chen, Peng-Qiao,Xiao, You-Cai,Chen, Ying-Chun
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supporting information
p. 5449 - 5452
(2014/06/09)
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- Oxidative rearrangements of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol: A general, regiospecific synthesis of α-aryl ketones
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The treatment of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol affords the corresponding α-aryl ketones. This oxidative rearrangement is general for acyclic and cyclic arylalkenes and permits regioselective syntheses of isomeric α-phenyl ketone pairs.
- Justik, Michael W.,Koser, Gerald F.
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p. 6159 - 6163
(2007/10/03)
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- Reduction of Ketene Dithioacetal S,S-Dioxides with Sodium Borohydride and Its Application to a Convenient Synthesis of Alkyl Arylmethyl Ketones
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The C-C double bond of a ketene dithioacetal S,S-dioxide was found to undergo reduction with sodium borohydride.This fact provides an efficient synthetic route from an aromatic aldehyde to an alkyl arylmethyl ketone using methylthiomethyl p-totyl sulfone.
- Ogura, Katsuyuki,Ohtsuki, Kazuo,Takahashi, Kazumasa,Iida, Hirotada
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p. 1597 - 1598
(2007/10/02)
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- Syntheses of Arylacetone and Arylacetonitrile by Friedel-Crafts Reaction with α-Chloro-α-(methylthio)-substituted Acetone and Acetonitrile
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Novel preparative methods for arylacetone and arylacetonitrile are described.Friedel-Crafts reactions of aromatic compounds with α-chloro-α-(methylthio)acetone (4) and α-chloro-α-(methylthio)acetonitrile (7) in the presence of Lewis acid afforded α-(methylthio)arylacetone (5) and α-(methylthio)arylacetonitrile (8), respectively.Compounds (5) and (8) were converted into the corresponding arylacetone (6) and arylacetonitrile (9) by reduction with zinc dust in acetic acid.Keywords: Friedel-Crafts reaction with α-chloro-α-(methylthio)acetone; Friedel-Crafts reaction with α-chloro-α-(methylthio)acetonitrile; α-(methylthio)arylacetone; α-(methylthio)arylacetonitrile; arylacetone; arylacetonitrile; reductive desulfurization; zinc dust-acetic acid
- Tamura, Yasumitsu,Choi, Hong Dae,Mizutani, Masako,Ueda, Yuko,Ishibashi, Hiroyuki
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p. 3574 - 3579
(2007/10/02)
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