- Silica gel-promoted synthesis of multisubstituted spiroindolenines from tryptamines and γ-chloro-α,β-unsaturated ketones
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Here we report a one-pot synthesis of multisubstituted spiroindolenines from a series of tryptamine derivatives with γ-chloro-α,β-unsaturated ketones. The reaction sequence consists of base-induced condensation and silica gel-promoted intramolecular Michael addition. The target molecules are afforded in up to 90% yield with up to >20:1 diastereoselectivity.
- Liu, Qiang-Qiang,Zheng, Chao,You, Shu-Li
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- An efficient keim-type catalyst based on an electron-poor P,O-chelate; tuning the selectivity of ethylene oligomerisation towards short α-olefins
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The tertiary phosphane Ph2P-pzONa, in which the phosphorus atom is substituted by an electron-withdrawing pyrazolonato unit, reacts with trans-[NiPhCl(PPh3)2] to afford quantitatively trans-P,P′-[NiPh(Ph2P-pzO)(
- Kuhn, Pierre,Semeril, David,Jeunesse, Catherine,Matt, Dominique,Lutz, Pierre,Welter, Richard
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- Formation of epoxychromeno[4,3-c]isoquinolines through diastereoselective one-pot IMDA reaction of 4-chloro-3-[(1E)-3-oxo-3-phenyl-1-propen-1-yl]-2H-chromen-2-one and furfurylamine
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Abstract: An intramolecular Diels–Alder mediated reaction of (2E)-3-(4-chloro-2-methylene-2H-chromen-3-yl)-1-phenyl-2-propen-1-one, which was obtained in situ from the reaction of 4-chloro-2-oxo-2H-chromene-3-carbaldehyde and Wittig reagent, with furfuryl
- Alizadeh, Abdolali,Amir Ashjei Asalemi, Kaveh,Farajpour, Behnaz,Halvagar, Mohammad Reza
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- Benzoylmethylenetriphenylphosphorane, C26H21OP
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The air-stable phosphorane (2-oxo-2-phenyltriphenylphosphoniumethylide) is shown to be a resonance hybrid of an ylene, ylidic and enolate canonical assembly.The geometry around the P atom is nearly tetrahedral.The O atom is oriented cis to the P atom.The phenyl ring of the benzoyl group is twisted with respect to the plane containing the carbonyl group.
- Kalyanasundari, M.,Panchanatheswaran, K.,Parthasarathi, V.,Robinson, Ward T.,Wen, Huo
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- Stereoselective Visible-Light Catalyzed Cyclization of Bis(enones): A Viable Approach to the Synthesis of Enantiomerically Enriched Cyclopentane Rings
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Photoredox catalytic cyclization of aryl enones in the presence of visible light, promoted either by metals or organic dyes, represent a valuable strategy for the synthesis of cycloalkanes. The development of a stereoselective version of such transformation, in the presence of the metal-free catalyst Eosin Y was studied, with the aim to realize an efficient protocol for the in-flow synthesis of enantiomerically enriched functionalized cyclopentane rings, taking advantage of the flow reactors technology. The use of a chiral auxiliary on the bisenone to be cyclized offers a straightforward and convenient option to exert a stereocontrol on the light-driven cyclization. By exploiting Evans’ oxazolidinones, the stereoselective light-driven cyclization affords, after the removal of the chiral auxiliary, a functionalized 1,2-trans cyclopentane ring in up to 83/17 enantiomeric ratio. When the reaction was performed in continuo, in a homemade coil photoreactor, high yields were observed. The cyclization was also successfully realized in a 3D-printed mesoreactor, without any change in the diastereoseletctivity of the process.
- Medici, Fabrizio,Resta, Simonetta,Presenti, Piero,Caruso, Lucia,Puglisi, Alessandra,Raimondi, Laura,Rossi, Sergio,Benaglia, Maurizio
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p. 4521 - 4524
(2021/06/12)
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- Synthesis of tertiary phosphine oxides by alkaline hydrolysis of quaternary phosphonium zwitterions using excess t-BuOK and stoichiometric water
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Hydrolysis of quaternary arylphosphonium zwitterions bearing COO? and those in situ generated from the corresponding salts bearing Ac or OH at the aryl ring by using excess t-BuOK and stoichiometric water affords tertiary arylphosphine oxides in moderate to excellent yield, in contrast to hydrolysis of these zwittertion or salts in aqueous NaOH that mainly provides phosphine oxides with the loss of the aryl group. Under the t-BuOK/water conditions, hydrolysis of carbonyl stabilized ylides Ph3P = CHCOR (R = Ph, Me, and OEt), which partially exist as phosphonium enolates, prefers to produce Ph2P(O)CH2COR. Further reduction of Ph2P(O)CH2COMe by PhSiH3 allows the preparation of Ph2PCH2COMe in 43% yield.
- Zhong, Chun-Hong,Huang, Wenhua
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p. 1537 - 1546
(2021/01/07)
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- Substituent effects in the formation of a few acenaphthenone-2-ylidene ketones and their molecular docking studies and in silico ADME profile
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We observed intriguing substituent effects in the reaction between 4-substituted acetophenones and acenaphthenequinone in the presence of KOH in methanol. In all cases, expected Claisen-Schimdt condensation was the first step. However, depending on the nature of 4-substituent on acetophenone, the initially formed condensation product remain unchanged or underwent Domino sequence of reactions to give three different 2:2 adducts arising through three distinct pathways. The interactions of acenaphthenone-2-ylidene ketones with the target proteins were performed by molecular docking studies. The prediction of in silico ADME belongings of the synthesized compounds revealed substantial drug-likeness characters based on Lipinski's rules.
- A, Jesna,Jacob, Jomon P.,Kuriakose, Daly,Thumpakara, Roshini K.
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- Selective Construction of C?C and C=C Bonds by Manganese Catalyzed Coupling of Alcohols with Phosphorus Ylides
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Herein, we report the manganese catalyzed coupling of alcohols with phosphorus ylides. The selectivity in the coupling of primary alcohols with phosphorus ylides to form carbon-carbon single (C?C) and carbon-carbon double (C=C) bonds can be controlled by the ligands. In the conversion of more challenging secondary alcohols with phosphorus ylides the selectivity towards the formation of C?C vs. C=C bonds can be controlled by the reaction conditions, namely the amount of base. The scope and limitations of the coupling reactions were thoroughly evaluated by the conversion of 21 alcohols and 15 ylides. Notably, compared to existing methods, which are based on precious metal complexes as catalysts, the present catalytic system is based on earth abundant manganese catalysts. The reaction can also be performed in a sequential one-pot reaction generating the phosphorus ylide in situ followed manganese catalyzed C?C and C=C bond formation. Mechanistic studies suggest that the C?C bond was generated via a borrowing hydrogen pathway and the C=C bond formation followed an acceptorless dehydrogenative coupling pathway. (Figure presented.).
- Liu, Xin,Werner, Thomas
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p. 1096 - 1104
(2020/12/31)
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- A Convenient Formal [4+2] Heterocylization Route to Bis(triflyl)tetrahydroquinolines
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We report the sustainable and efficient synthesis of a new type of quinoline derivatives bearing one or two SO2CF3 groups. The protocol is metal-, catalyst- and irradiation-free, involves the use of readily available and stable precursors, and avoids the formation of side products. Also, the mild conditions of the process allow the tolerance of a wide range of functional groups.
- Lázaro-Milla, Carlos,Almendros, Pedro
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supporting information
p. 13534 - 13538
(2021/08/13)
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- Rh(iii)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienonesviaC(sp2)-H bond activation
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Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienonesviaRh(iii)-catalyzed C-H activation ofN-methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity. Furthermore, mechanistic studies of arylative cyclization and a gram-scale experiment are also presented.
- Chegondi, Rambabu,Jadhav, Sandip B.,Maurya, Sundaram,Navaneetha, N.
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supporting information
p. 13598 - 13601
(2021/12/23)
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- 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 Influence of Substitution on Thiol-Induced Oxanorbornadiene Fragmentation
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Oxanorbornadienes (ONDs) undergo facile Michael addition with thiols and then fragment by a retro-Diels-Alder (rDA) reaction, a unique two-step sequence among electrophilic cleavable linkages. The rDA reaction rate was explored as a function of the furan
- De Pascalis, Lucrezia,Yau, Mei-Kwan,Svatunek, Dennis,Tan, Zhuoting,Tekkam, Srinivas,Houk,Finn
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supporting information
p. 3751 - 3754
(2021/05/10)
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- Nickel-catalyzed remote hydrosilylation of unconjugated enones with bulky triphenylsilane
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Herein we describe a nickel-catalyzed remote hydrosilylation of unconjugated enones with bulky triphenylsilane. A range ofZ-silyl enol ethers are obtained as major isomers due to the process of nickel triggered alkene isomerization. Notably, some specific
- Chen, Xue,Jin, Hongwei,Liu, Yunkui,Wang, Zhen,Zhou, Bingwei,Zhou, Jinyong
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supporting information
p. 8021 - 8024
(2021/10/04)
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- Catalytic Synthesis of 1 H-2-Benzoxocins: Cobalt(III)-Carbene Radical Approach to 8-Membered Heterocyclic Enol Ethers
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The metallo-radical activation of ortho-allylcarbonyl-aryl N-arylsulfonylhydrazones with the paramagnetic cobalt(II) porphyrin catalyst [CoII(TPP)] (TPP = tetraphenylporphyrin) provides an efficient and powerful method for the synthesis of novel 8-membered heterocyclic enol ethers. The synthetic protocol is versatile and practical and enables the synthesis of a wide range of unique 1H-2-benzoxocins in high yields. The catalytic cyclization reactions proceed with excellent chemoselectivities, have a high functional group tolerance, and provide several opportunities for the synthesis of new bioactive compounds. The reactions are shown to proceed via cobalt(III)-carbene radical intermediates, which are involved in intramolecular hydrogen transfer (HAT) from the allylic position to the carbene radical, followed by a near-barrierless radical rebound step in the coordination sphere of cobalt. The proposed mechanism is supported by experimental observations, density functional theory (DFT) calculations, and spin trapping experiments.
- De Bruin, Bas,De Zwart, Felix J.,Li, Zirui,Mathew, Simon,Wolzak, Lukas A.,Zhou, Minghui
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supporting information
p. 20501 - 20512
(2021/12/03)
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- Asymmetric Catalytic Diverse Ring Opening/Cycloadditions of Cyclobutenones with (E)-Alkenyloxindoles and (E)-Dioxopyrrolidines
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Highly enantioselective ring-opening/cycloaddition reactions of cyclobutenones were achieved by employing chiral N,N′-dioxide/metal complexes as the catalysts. The Diels-Alder type cycloaddition with (E)-alkenyloxindoles yielded spirocyclohexaneoxindoles with excellent results. Meanwhile, a hetero-Diels-Alder process occurred with (E)-dioxopyrrolidines to afford spiropyrrolidinone-dihydropyranone derivatives.
- Luo, Yao,Zhang, Hang,Wang, Siyuan,Zhou, Yuqiao,Dong, Shunxi,Feng, Xiaoming
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supporting information
p. 2645 - 2650
(2020/04/02)
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- Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor
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A convergent strategy is reported for the construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8-tetrahydrocinnoline) derivatives in moderate to excellent yields.
- Abdelli, Abderrahmen,Efrit, Mohamed Lotfi,El-Marrouki, Dalel,Gros, Philippe C.,M’Rabet, Hédi,Touchet, Sabrina
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supporting information
p. 1722 - 1731
(2021/06/25)
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- Copper-Catalyzed N-O Cleavage of α,β-Unsaturated Ketoxime Acetates toward Structurally Diverse Pyridines
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The copper-catalyzed [4 + 2] annulation of α,β-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.
- Ding, Xiaojuan,Duan, Jindian,Fang, Zheng,Guo, Kai,Li, Zhenjiang,Mao, Yiyang,Rong, Binsen,Xu, Gaochen,Zhang, Lei,Zhu, Ning
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supporting information
p. 2532 - 2542
(2020/03/13)
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- C(sp2)-H Bond Multiple Functionalization in Air for Construction of Tetrahydrocarbazoles with Continuous Quaternary Carbons and Polycyclic Diversification
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The C(sp2)-H function of indole ketone with diazo compound via a rhodium(II)-catalyzed intramolecular electrophilic trapping reaction under mild conditions in air was demonstrated. The established methodology provided a highly efficient approach for direct synthesis of mutisubstituted tetrahydrocarbazoles with continuous quaternary carbons. The resulting products facilitate further modification to conveniently construct tetrahydrocarbazoles with additional fused heterocyclic rings. By phenotypic screening, several products exhibit good anticancer bioctivities in osteosarcoma cell lines.
- Dong, Suzhen,Jia, Shikun,Liu, Shunying,Ni, Dan,Pi, Rou,Song, Longlong,Tang, Jie,Yang, Fan
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- Visible-light driven synthesis of polycyclic benzo[: D] [1,3]oxazocine from 2-aminochalcone
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Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.
- Chen, Junhan,Gao, Yu-Qi,He, Yu-Peng,Hou, Yi,Li, Ruoxin,Xie, Weiqing,Zhang, Sheng-Yong,Zhu, Liming
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supporting information
p. 6739 - 6742
(2020/07/13)
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- Remote Functionalization of α,β-Unsaturated Carbonyls by Multimetallic Sequential Catalysis
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The remote functionalization of α,β-unsaturated carbonyls by an array of multimetallic sequential catalytic systems is described. The reactions are triggered by hydrometalation using [Pd-H] or [Ru-H] isomerization catalysts and driven by the formation of thermodynamically more stable 1,2-vinyl arenes. The Pd-catalyzed deconjugative isomerization was combined with a Cu-catalyzed β-borylation of the transiently generated styrenyl derivatives to deliver a range of products that would not be accessible with the use of a single catalyst. [Pd/Cu] catalytic systems were also identified for the highly enantioselective α-hydroboration and α-hydroamination of the styrenyl intermediates. Difunctionalization simultaneously at the benzylic and homobenzylic positions was achieved by combining the isomerization process with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples. Starting from a simple α,β-unsaturated ester, an isomerization/dihydroxylation/lactonization sequence gave access to a naturally occurring γ-butyrolactone in good yield, with excellent diastereo- and enantioselectivity.
- Romano, Ciro,Fiorito, Daniele,Mazet, Clément
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supporting information
p. 16983 - 16990
(2019/10/28)
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- A Ba/Pd Catalytic System Enables Dehydrative Cross-Coupling and Excellent E-Selective Wittig Reactions
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A Ba/Pd cooperative catalysis system was developed to enable the dehydrative cross-coupling of allylic alcohols with P-ylides to occur directly and promote a subsequent Wittig reaction in one pot. A variety of multisubstituted 1,4-dienes were isolated in good to excellent yields with broad P-ylides (stabilized by both ester and ketone carbonyl groups) and aldehyde (aliphatic and aromatic) substrates with excellent E selectivity.
- Xie, Peizhong,Fu, Weishan,Cai, Xinying,Sun, Zuolian,Wu, Ying,Li, Shuangshuang,Gao, Cuiqing,Yang, Xiaobo,Loh, Teck-Peng
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supporting information
p. 7055 - 7059
(2019/09/12)
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- PYRROLIDINE DERIVATIVES AS PPAR AGONISTS
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The present invention discloses a class of pyrrolidine derivatives as PPAR agonist, and their use for the treatment of some diseases of PPAR receptor-associated pathways (such as nonalcoholic steatohepatitis and concurrent fibrosis, insulin resistance, primary biliary cholgangitis, dyslipidenmia, hyperlipidemia, hypercholesterolemia, atherosclerosis, hypertriglyceridemia, cardiovascular disease, obesity or the like). In particular, the present invention discloses a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.
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Paragraph 0693; 0696-0698
(2019/08/02)
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- Organocatalytic Enantioselective Selenosulfonylation of a C-C Double Bond to Form Two Stereogenic Centers in an Aqueous Medium
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Organocatalytic selenosulfonylation of the C-C double bond of α,β-unsaturated ketones to construct two contiguous stereogenic centers in an aqueous medium was described. A series of α-selenyl and β-sulfonyl ketones with various functional groups were synthesized in good yields and enantioselectivities with saturated NaCl solution as the solvent. In addition, this protocol had been successfully scaled up to a decagram scale via a simple workup procedure.
- Chen, Zhili,Hu, Fangli,Huang, Shengli,Zhao, Zhengxing,Mao, Hui,Qin, Wenling
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p. 8100 - 8111
(2019/06/17)
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- Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones: Via tandem arylative cyclization
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The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.
- Jadhav, Sandip B.,Thopate, Satish B.,Nanubolu, Jagadeesh Babu,Chegondi, Rambabu
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supporting information
p. 1937 - 1946
(2019/02/20)
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- Polysubstituted 1,4-diene compound and preparation method thereof
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The invention discloses a polysubstituted 1,4-diene compound and a preparation method thereof. The method comprises the following steps: adding an allyl alcohol raw material, phosphorus ylide with stable carbonyl/ester, barium bis(trifluoromethylsulfonyl)imide, and a 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex into a reaction solvent in sequence, and performing a catalytic reaction for 46-50 h under argon atmosphere, the temperature of 98-102 DEG C and a stirring state; adding aldehyde into a reaction system, continuing to react for 11-13 h under room temperature, extracting for removing the reaction solvent in reaction liquid, and purifying to obtain the polysubstituted 1,4-diene compound. The method disclosed by the invention is wide in application range of substrates; a reaction by-product is only water; the method is environmentally friendly, simple in operation, non-toxic and harmless, easily-available in raw materials and high in yield, and has excellent economical efficiency; moreover, the polysubstituted 1,4-diene compound obtained by the method is an excellent chemical synthesis reagent and plays an important role in synthetic chemistry and drug synthesis.
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Paragraph 0037-0039
(2019/10/08)
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- Tandem Wittig Reaction-Ring Contraction of Cyclobutanes: A Route to Functionalized Cyclopropanecarbaldehydes
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An original tandem reaction consisting of a Wittig reaction-ring contraction process between α-hydroxycyclobutanone and phosphonium ylides has been developed. Highly functionalized cyclopropanecarbaldehydes are obtained in good to high yield.
- Aitken, David J.,Caboni, Pierluigi,Cuccu, Federico,Frongia, Angelo,Luridiana, Alberto,Secci, Francesco,Serusi, Lorenzo
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supporting information
(2019/10/08)
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- Fe-Catalyzed Cycloisomerization of Aryl Allenyl Ketones: Access to 3-Arylidene-indan-1-ones
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A cycloisomerization of aryl allenyl ketones to 3-arylidene-indan-1-ones using a cationic Fe-complex as a catalyst is reported. The catalyst opens a synthetically interesting reaction pathway to this surprisingly underrepresented class of indanones that are not accessible using alternative catalytic systems.
- Teske, Johannes,Plietker, Bernd
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supporting information
p. 2257 - 2260
(2018/04/27)
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- Generation and Rearrangement of N,O-Dialkenylhydroxylamines for the Synthesis of 2-Aminotetrahydrofurans
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A new diastereoselective route to 2-aminotetrahydrofurans has been developed from N,O-dialkenylhydroxylamines. These intermediates undergo a spontaneous C?C bond-forming [3,3]-sigmatropic rearrangement followed by a C?O bond-forming cyclization. A copper-catalyzed N-alkenylation of an N-Boc-hydroxylamine with alkenyl iodides, and a base-promoted addition of the resulting N-hydroxyenamines to an electron-deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base-promoted ring-opening and Mannich reaction has been discovered to covert 2-aminotetrahydrofurans to cyclopentyl β-aminoacid derivatives or cyclopentenones.
- Son, Jongwoo,Reidl, Tyler W.,Kim, Ki Hwan,Wink, Donald J.,Anderson, Laura L.
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supporting information
p. 6597 - 6600
(2018/05/03)
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- Catalytic Cyclooligomerization of Enones with Three Methylene Equivalents
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Cyclic structures are highly represented in organic molecules, motivating a wealth of catalytic methods targeting their synthesis. Among the various ring-forming processes, cyclooligomerization reactions possess several attractive features but require addressing a unique challenge associated with controlling ring-size selectivity. Here we describe the catalytic reductive cocyclooligomerization of an enone and three carbene equivalents to generate a cyclopentane, a process that constitutes a formal [2 + 1 + 1 + 1]-cycloaddition. The reaction is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn as the C1 component. Mechanistic studies are consistent with a metallacycle-based pathway, featuring sequential migratory insertions of multiple carbene equivalents to yield cycloalkanes larger than cyclopropanes.
- Farley, Conner M.,Zhou, You-Yun,Banka, Nishit,Uyeda, Christopher
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supporting information
p. 12710 - 12714
(2018/10/09)
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- Nonenzymatic Dynamic Kinetic Resolution of in situ Generated Hemithioacetals: Access to 1,3-Disubstituted Phthalans
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The first nonenzymatic DKR reaction of hemithioacetals is developed. Hemithioacetals were formed in situ via thiol addition and subsequently underwent an intramolecular oxa-Michael reaction. The scope of the reaction was quite broad ranging from aliphatic to aromatic substituents and 1,3-disubstituted-1,3-dihyroisobenzofuran products were obtained in good yields with moderate diastereoselectivities and high enantioselectivities. (Figure presented.).
- Nath, Utpal,Chowdhury, Deepan,Pan, Subhas Chandra
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supporting information
p. 1628 - 1633
(2018/03/21)
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- Nickel-catalyzed, ligand-free, diastereoselective synthesis of 3-methyleneindan-1-ols
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Nickel-catalyzed, highly diastereoselective annulations between activated allenes and 2-acetylarylboronic acid or 2-formylarylboronic acids are reported. No ligand for nickel is required, and the reactions proceed efficiently at room temperature to give a broad range of substituted 3-methyleneindan-1-ols. Preliminary results of an enantioselective variant are also described.
- Panchal, Heena,Clarke, Christopher,Bell, Charles,Karad, Somnath Narayan,Lewis, William,Lam, Hon Wai
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supporting information
p. 12389 - 12392
(2018/11/20)
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- Synthesis of trifluoromethyl-/cyclopropyl-substituted 2-isoxazolines by DBU-promoted domino reaction
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NTrifluoromethyl and cyclopropyl substituted 2-isoxazolines were synthesized via a DBU-promoted domino reaction of β-trifluoromethyl-/β-cyclopropyl-substituted enones with hydroxylamine. The domino reaction consists of a Michael addition and the followed cyclization. A wide range of 3-substituted 5-cyclopropyl-5- trifluoromethyl-2-isoxazolines were obtained in good to excellent yields under mild reaction conditions. The method could also apply to other trifluoromethyl-substituted enones.
- Liu, Xiao-Dong,Ma, Hai-Yan,Xing, Chun-Hui,Lu, Long
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supporting information
p. 1780 - 1783
(2017/07/27)
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- Synthesis of Oxatricyclooctanes via Photoinduced Intramolecular Oxa-[4+2] Cycloaddition of Substituted o-Divinylbenzenes
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The photolysis of substituted o-divinylbenzenes promotes a one-step and metal-free conversion to oxatricycles at room temperature. Irradiation o-divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition to form oxacyclic derivatives.
- Liu, Qiang,Wang, Junlei,Li, Dazhi,Gao, Guo-Lin,Yang, Chao,Gao, Yuan,Xia, Wujiong
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p. 7856 - 7868
(2017/08/14)
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- A Direct Synthesis of Highly Substituted π-Rich Aromatic Heterocycles from Oxetanes
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The ubiquitous use of π-rich five-membered heterocycles has driven the development of new methods for their synthesis for more than a century. Here, we disclose a general and reliable reaction manifold for the construction of highly substituted heterocycles through a facile Lewis-acid-catalyzed oxetane rearrangement. Notably, this methodology employs a keto-oxetane motif as a 1,4-dicarbonyl surrogate, which can be synthesized using robust alkylation or alkenylation reactions, and thus obviates the need to access 1,4-dicarbonyl compounds via umpoled starting materials. We harnessed this reactivity to generate a broad range of substituted furans and pyrroles, and extended this methodology to produce benzo-fused versions thereof.
- White, Alexander R.,Kozlowski, Ryan A.,Tsai, Shiou-Chuan,Vanderwal, Christopher D.
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supporting information
p. 10525 - 10529
(2017/08/22)
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- A convenient synthesis of 4-alkyl-3-benzoylpyrroles from α,β-unsaturated ketones and tosylmethyl isocyanide
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A convenient synthesis of 4-alkyl-3-benzoyl pyrrole was achieved from α,β-unsaturated ketones and tosylmethyl isocyanide in the presence of mild base LiOH·H2O. This method is very economical and was successfully utilized for the synthesis of various 4-alkyl-3-benzoylpyrrole derivatives with good to excellent yields.
- Kumar, Kapil,More, Shital S.,Goyal, Sandeep,Gangar, Mukesh,Khatik, Gopal L.,Rawal, Ravindra K.,Nair, Vipin A.
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supporting information
p. 2315 - 2319
(2016/05/10)
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- Transaminase Triggered Aza-Michael Approach for the Enantioselective Synthesis of Piperidine Scaffolds
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The expanding “toolbox” of biocatalysts opens new opportunities to redesign synthetic strategies to target molecules by incorporating a key enzymatic step into the synthesis. Herein, we describe a general biocatalytic approach for the enantioselective preparation of 2,6-disubstituted piperidines starting from easily accessible pro-chiral ketoenones. The strategy represents a new biocatalytic disconnection, which relies on an ω-TA-mediated aza-Michael reaction. Significantly, we show that the reversible enzymatic process can power the shuttling of amine functionality across a molecular framework, providing access to the desired aza-Michael products.
- Ryan, James,?iau?iulis, Mindaugas,Gomm, Andrew,Maciá, Beatriz,O’Reilly, Elaine,Caprio, Vittorio
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supporting information
p. 15798 - 15800
(2016/12/22)
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- Enantioselective Organocatalytic Cascade Approach to Different Classes of Benzofused Acetals
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A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ-keto-α,β-unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5-fused acetals with two stereocenters—the tetrahydrofurobenzofuran scaffolds—proceeds in moderate yields and up to 96 % ee. The other reaction pathway provides 5,6-bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 % ee. The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25 mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.
- Paz, Bruno Matos,Klier, Lydia,N?sborg, Line,Lauridsen, Vibeke Henriette,Jensen, Frank,J?rgensen, Karl Anker
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supporting information
p. 16810 - 16818
(2016/11/16)
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- Organocatalytic Redox Isomerization of Electron-Deficient Allylic Alcohols: Synthesis of 1,4-Ketoaldehydes
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An organocatalytic redox isomerization strategy has been developed for the synthesis of 1,4-ketoaldehydes. DABCO was found to be the best catalyst for the isomerization of -hydroxy enones. With 20 mol % of DABCO as catalyst and DMSO as the solvent high yi
- Mondal, Keshab,Mondal, Buddhadeb,Pan, Subhas Chandra
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p. 4835 - 4840
(2016/07/06)
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- Enantioselective Stereodivergent Nucleophile-Dependent Isothiourea-Catalysed Domino Reactions
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α,β-Unsaturated acyl ammoniums generated from the reaction of α,β-unsaturated 2,4,6-trichlorophenol (TCP) esters bearing a pendent enone with an isothiourea organocatalyst are versatile intermediates in a range of enantioselective nucleophile-dependent domino processes to form complex products of diverse topology with excellent stereoselectivity. Use of either 1,3-dicarbonyls, acyl benzothiazoles, or acyl benzimidazoles as nucleophiles allows three distinct, diastereodivergent domino reaction pathways to be accessed to form various fused polycyclic cores containing multiple contiguous stereocentres.
- Matviitsuk, Anastassia,Taylor, James E.,Cordes, David B.,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 17748 - 17757
(2016/11/29)
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- Enantioselective synthesis of 2,3-disubstituted: Trans -2,3-dihydrobenzofurans using a Br?nsted base/thiourea bifunctional catalyst
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The diastereo- and enantioselective synthesis of 2,3-disubstituted trans-2,3-dihydrobenzofuran derivatives (15 examples, up to 96 : 4 dr, 95 : 5 er) via intramolecular Michael addition has been developed using keto-enone substrates and a bifunctional tertiary amine-thiourea catalyst. This methodology was extended to include non-activated ketone pro-nucleophiles for the synthesis of 2,3-disubstituted indane and 3,4-disubstituted tetrahydrofuran derivatives.
- Barrios Antúnez, Diego-Javier,Greenhalgh, Mark D.,Fallan, Charlene,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 7268 - 7274
(2016/08/05)
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- Tailoring flavins for visible light photocatalysis: organocatalytic [2+2] cycloadditions mediated by a flavin derivative and visible light
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A new application of flavin derivatives in visible light photocatalysis was found. 1-Butyl-7,8-dimethoxy-3-methylalloxazine, when irradiated by visible light, was shown to allow an efficient cyclobutane ring formation via an intramolecular [2+2] cycloaddition of both styrene dienes, considered as electron-rich substrates, and electron-poor bis(arylenones), presumably proceeding via an energy transfer mechanism.
- Mojr, Viktor,Svobodová, Eva,Straková, Karolína,Nevesely, Tomá?,Chudoba, Josef,Dvo?áková, Hana,Cibulka, Radek
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supporting information
p. 12036 - 12039
(2015/07/28)
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- Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
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An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.
- Wei, Hongbo,Li, Yun,Xiao, Ke,Cheng, Bin,Wang, Huifei,Hu, Lin,Zhai, Hongbin
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supporting information
p. 5974 - 5977
(2016/01/09)
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- Asymmetric 1,4-Conjugate Addition of Diarylphosphines to α,β,γ,δ-Unsaturated Ketones Catalyzed by Transition-Metal Pincer Complexes
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An enantioselective asymmetric 1,4-addition of diarylphosphines to linear α,β,γ,δ-unsaturated dienones was developed. A series of chiral PCP- and PCN-transition-metal (Pd, Pt and Ni) pincers, themselves prepared catalytically via asymmetric hydrophosphination, were sequentially screened to reveal the roles of backbone architecture and metal ion in catalyst design. The selected ester-functionalized PCP-palladium pincer afforded the chiral 1,4-phosphine adducts in excellent yields with up to >99% ee. The same catalyst when utilized for the hydrophosphination of an α,β,γ,δ-unsaturated malonate ester also revealed the critical role played by the ester functionality on the ligand backbone in dictating the enantioselectivity of the 1,6-adduct.
- Yang, Xiang-Yuan,Tay, Wee Shan,Li, Yongxin,Pullarkat, Sumod A.,Leung, Pak-Hing
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supporting information
p. 5196 - 5201
(2015/11/09)
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- Successively recycle waste as catalyst: A one-pot wittig/1,4-reduction/paal-knorr sequence for modular synthesis of substituted furans
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A one-pot tandem Wittig/conjugate reduction/Paal-Knorr reaction is reported for the synthesis of di- or trisubstituted furans. This novel sequence first demonstrates the possibility of successively recycling waste from upstream steps to catalyze downstream reactions.
- Chen, Long,Du, Yi,Zeng, Xing-Ping,Shi, Tao-Da,Zhou, Feng,Zhou, Jian
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supporting information
p. 1557 - 1560
(2015/03/30)
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- Domino reaction sequences leading to the formation of 2:2 adducts between acenaphthenequinone and acetophenone
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A Michael-aldol domino reaction sequence of acenaphthenequinone with acetophenone in the presence of KOH in methanol solvent leading to the formation of three different 2:2 adducts arising through three distinct reaction sequences is described. Similar sequences leading to a highly substituted furan derivative were observed in the reaction between phenanthrenequinone and acetophenone.
- Jacob, Jomon P.,Kunjachan, Christy,Sajitha,Thumpakara, Roshini K.,Rakesh,Nidhisha,Unnikrishnan, Perupparampil A.,Prathapan, Sreedharan
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p. 127 - 138
(2015/02/19)
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- Identification of novel chromenone derivatives as interleukin-5 inhibitors
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A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity. Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor. However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor. Meanwhile the potent activity profile of compounds 5 was discovered. This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure. The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety.
- Venkateswararao, Eeda,Kim, Min-Seok,Sharma, Vinay K.,Lee, Ki-Cheul,Subramanian, Santhosh,Roh, Eunmiri,Kim, Youngsoo,Jung, Sang-Hun
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- Inner workings of a cinchona alkaloid catalyzed oxa-Michael cyclization: Evidence for a concerted hydrogen-bond-network mechanism
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Cinchona alkaloids catalyze the oxa-Michael cyclization of 4-(2-hydroxyphenyl)-2-butenoates to benzo-2,3-dihydrofuran-2-yl acetates and related substrates in up to 99 % yield and 91 % ee (ee=enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen-bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra-Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C-2 of the substrate shows that addition of RO-H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism-based specificity. A concerted hydrogen-bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α-carbanionic center of the product enolate. The importance of concerted hydrogen-bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4-additions. Secret of cyclization: The cinchona alkaloid catalyzed asymmetric oxa-Michael cyclization of 2′-hydroxyphenyl-2-butenoates to benzodihydrofurans proceeds by a highly enantio- and diastereoselective syn-specific addition mode (see scheme). Transition-state activation of the carbonyl group by hydrogen bonding to the catalyst is excluded. This represents a clear-cut demonstration of the importance of concerted hydrogen-bond network mechanisms in cinchona-based asymmetric organocatalysis. Copyright
- Hintermann, Lukas,Ackerstaff, Jens,Boeck, Florian
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p. 2311 - 2321
(2013/04/10)
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- Isothiourea-mediated one-pot synthesis of functionalized pyridines
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Acids to bases: The synthesis of 2,4,6-trisubstituted pyridines from (phenylthio)acetic acid and a range of α,β-unsaturated ketimines is reported. This process proceeds by intermolecular Michael addition/ lactamization, thiophenol elimination, and N- to O
- Stark, Daniel G.,Morrill, Louis C.,Yeh, Pei-Pei,Slawin, Alexandra M. Z.,O'Riordan, Timothy J. C.,Smith, Andrew D.
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supporting information
p. 11642 - 11646
(2013/11/06)
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- Methylene-bridged bis(imidazoline)-derived 2-oxopyrimidinium salts as catalysts for asymmetric Michael reactions
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In nothing flat: The title salts, having planar nitrogen centers, were utilized successfully as phase-transfer catalysts for asymmetric Michael reactions of tert-butyl glycinate benzophenone Schiff base with vinyl ketone and chalcone derivatives, thus providing excellent levels of diastereo- and enantiocontrol (see scheme). Copyright
- Sheshenev, Andrey E.,Boltukhina, Ekaterina V.,White, Andrew J. P.,Hii, King Kuok
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supporting information
p. 6988 - 6991
(2013/07/25)
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- Synthesis, structure, and ethylene polymerization behavior of nickel complexes based on benzoylmethylenetri(2-alkoxylphenyl)phosphorane
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Several new nickel complexes are prepared by the treatment of the stabilized ylide benzoylmethylenetri(2-alkoxylphenyl)phosphorane with Ni(cod)2 in the presence of PPh3. X-Ray diffraction studies reveal that a distorted square planar geometry around Ni(ii) is adopted. Upon treatment with Ni(cod)2, the nickel complexes are sufficiently robust for ethylene polymerization. The existence of 2-alkoxyl-aryl substituents on phosphorus improves the catalytic activities. The highest activity (2.1 × 106 g mol-1 h-1) is achieved when tri(2-isopropoxy-phenyl)phosphorane is employed (5e), which is one order higher than the corresponding SHOP catalyst. NMR analysis shows that the polyethylene mainly contains terminal double bonds and is highly linear.
- Wan, Da-Wei,Gao, Yan-Shan,Li, Jun-Fang,Shen, Qi,Sun, Xiu-Li,Tang, Yong
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p. 4552 - 4557
(2012/07/02)
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- Kinetics and mechanism of gas-phase pyrolysis of ylides. Part 3. 1 Thermal reactivity of α-carbonyl- and thiocarbonyl-stabilized methylenetriphenylphosphoranes
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Fourteen ketone/thione-stabilized triphenylphosphonium methylides were subjected to conventional gas-phase and flash vacuum pyrolysis (FVP). The kinetics of the first-order thermal gas-phase reactions of all these compounds were investigated over 360-653K temperature range. The values of the Arrhenius logA and energy of activation of these ylides averaged 11.52±0.34s -1 and 133.20±3.14kJmol-1, respectively. The products of sealed-tube (static) and FVP were analyzed and compared. A mechanism is proposed to account for the products of reaction. The rate constants [k (s-1)] of the substrates at 500K were calculated and used to substantiate the proposed mechanism of pyrolysis, and to rationalize the thermal gas-phase reactivities of the ylides under study.
- Al-Bashir, Rasha F.,Al-Awadi, Nouria A.,El-Dusouqui, Osman M. E.
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experimental part
p. 311 - 319
(2012/04/17)
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- Stereoselective olefination of N-sulfonyl imines with stabilized phosphonium ylides for the synthesis of electron-deficient alkenes
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An unprecedented protocol has been developed for thestereoselective synthesis of structurally diverse electron-deficient alkenes in moderate to excellent yields from readily accessible N-sulfonyl imines and stabilized phosphonium ylides. Significantly, the olefination reaction of N-sulfonylimines with nitrile-stabilized phosphonium ylides affords an array of α,β-unsaturated nitriles with high Z selectivity, and the reactions with ester-, amide-, and ketone-stabilized phosphonium ylides afford α,β-unsaturated esters, amides, and ketones with high E selectivity, respectively. Spectroscopic analysis of the reaction mixtures and trapping of the intermediates allow plausible mechanisms to be proposed. Initialimine/ylide addition leads to the formation of betaines that cyclize to form 1,2-azaphosphetanes that subsequently eliminate iminophosphoranes to yield alkenes. For the synthesis of electron-deficient 1,2-disubstituted alkenes, the presence of an electron-withdrawing group in the betaine allows rapid interconversion between its two diastereomers through proton transfer. The Z/E selectivity for alkene synthesis is determined by the different rates at which the two betaine diastereomers form the corresponding 1,2-azaphosphetane diastereomers. In contrast, the Z/E selectivity for the synthesis of electron-deficient trisubstituted alkenes originates from the diastereoselective addition of stabilized phosphonium ylides to N-sulfonyl imines.
- Fang, Fan,Li, Yuan,Tian, Shi-Kai
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supporting information; experimental part
p. 1084 - 1091
(2011/04/15)
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