- Synthesis and biological evaluation of novel radioiodinated benzimidazole derivatives for imaging α-synuclein aggregates
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α-Synuclein (α-syn) aggregates are commonly found in the brains of patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and some other diseases. Therefore, in vivo imaging of α-syn aggregates would aid in drug development, early diagno
- Watanabe, Hiroyuki,Ariyoshi, Taisuke,Ozaki, Akihiko,Ihara, Masafumi,Ono, Masahiro,Saji, Hideo
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- A structural study of Troger's base scaffold-based dyes for DSSC applications
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Three Troger's base scaffold-based metal-free sensitizers TD1, TD2 and TD3 with triphenylamine donor and rhodanine-3-acetic acid as an acceptor/anchoring group were designed and synthesized for dye-sensitized solar cells. The sensitizer series was designed to investigate the influence of the poly[n]enic (from n?=?0 to 2) backbones and their anchoring effect in DSSCs. Optical, electrochemical and photovoltaic properties were compared with analogues dyes D1-D3 possessing one anchoring group. It has been proven that the extended polymethine chains ensure flexibility of these units and inspire the interaction between two chromophores promoting aggregate formation in these Troger's base-based dyes.
- Urnikaite, Simona,Braukyla, Titas,Magomedov, Artiom,Kamarauskas, Egidijus,Malinauskas, Tadas,Getautis, Vytautas
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- Cis-Enals in N-heterocyclic carbene-catalyzed reactions: Distinct stereoselectivity and reactivity
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The first successful generation of cis-homoenolate equivalents from cis-enals under the catalysis of N-heterocyclic carbenes (NHCs) has been realized. The cis-homoenolate intermediates undergo effective reactions with α,β-unsaturated imines to afford chir
- Chen, Xingkuan,Fang, Xinqiang,Chi, Yonggui Robin
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Read Online
- An efficient Pd@Pro-GO heterogeneous catalyst for the α, β-dehydrogenation of saturated aldehyde and ketones
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An Efficient Pd@Pro-GO heterogeneous catalyst was developed that can promote the α, β-dehydrogenation of saturated aldehyde and ketones in the yield of 73% ? 92% at mild conditions without extra oxidants and additives. Pd@Pro-GO heterogeneous catalyst was synthesized via two steps: firstly, the Pro-GO was obtained by the esterification reaction between graphene oxide (GO) and N-(tert-Butoxycarbonyl)-L-proline (Boc-Pro-OH), followed by removing the protection group tert-Butoxycarbonyl (Boc), which endowed the proline-functionalized GO with both the lewis acid site (COOH) and the bronsted base site (NH), besides, the pyrrolidine of proline also can form imine with aldehydes to activate these substrates; Second, palladium was dispersed on the proline-functionalized GO (Pro-GO) to obtained heterogeneous catalyst Pd@Pro-GO. Mechanistic studies have shown that the Pd@Pro-GO-catalyzed α,β-dehydrogenation of saturated aldehyde and ketones was realized by an improved heterogeneously catalyzed Saegusa oxidation reaction. Based on the obove characteristics, the Pd@Pro-GO will be widely used in the transition metal catalytic field.
- Pan, Gao-Fei,Wang, Zhe,Chang, Yi-Yuan,Hao, Yue,Wang, Yi-Chen,Xing, Rui-Guang
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supporting information
(2021/12/30)
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- Enantioselective Organocatalytic Synthesis of 1,2,3-Trisubstituted Cyclopentanes
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An organocatalytic asymmetric domino Michael/α-alkylation reaction between enals and non-stabilized alkyl halides has been developed. Chiral secondary amine catalyzed cyclization reaction of 1-bromo-3-nitropropane with α,β-unsaturated aldehydes provides 1,2,3-trisubstituted cyclopentane carbaldehydes with high diastereo- (dr up to 8 : 1) and enantioselectivities (ee up to 96 %).
- ?otolová, Martina,Kamlar, Martin,Reme?, Marek,Géant, Pierre-Yves,Císa?ová, Ivana,?tícha, Martin,Vesely, Jan
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p. 5080 - 5089
(2021/09/30)
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- Selective Rhodium-Catalyzed Hydroformylation of Terminal Arylalkynes and Conjugated Enynes to (Poly)enals Enabled by a π-Acceptor Biphosphoramidite Ligand
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The hydroformylation of terminal arylalkynes and enynes offers a straightforward synthetic route to the valuable (poly)enals. However, the hydroformylation of terminal alkynes has remained a long-standing challenge. Herein, an efficient and selective Rh-catalyzed hydroformylation of terminal arylalkynes and conjugated enynes has been achieved by using a new stable biphosphoramidite ligand with strong π-acceptor capacity, which affords various important E-(poly)enals in good yields with excellent chemo- and regioselectivity at low temperatures and low syngas pressures.
- Zhao, Jiangui,Zheng, Xueli,Tao, Shaokun,Zhu, Yuxin,Yi, Jiwei,Tang, Songbai,Li, Ruixiang,Chen, Hua,Fu, Haiyan,Yuan, Maolin
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supporting information
p. 6067 - 6072
(2021/08/16)
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- One-Pot Preparation of (E)-α,β-Unsaturated Aldehydes by a Julia-Kocienski Reaction of 2,2-Dimethoxyethyl PT Sulfone Followed by Acid Hydrolysis
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(E)-α,β-Unsaturated aldehydes were synthesized by the Julia-Kocienski reaction of 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfone 3 with various aldehydes, followed by acid hydrolysis. The reaction could be carried out in one pot, and various (E)-α,β-unsaturated aldehydes were obtained in a short time and with high yields.
- Ando, Kaori,Watanabe, Haruka,Zhu, Xiaoxian
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p. 6969 - 6973
(2021/05/06)
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- Substrate-Controlled Chemo-/Enantioselective Synthesis of α-Benzylated Enals and Chiral Cyclopropane-Fused 2-Chromanone Derivatives
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Substrate-controlled cascade reactions between α,β-unsaturated aldehydes or their analogues and 2,4-dinitrobenzyl chloride in the presence of a chiral secondary amine as the catalyst and base were developed, to obtain a broad spectrum of α-benzylated enals and enantioenriched cyclopropane-fused chroman-2-one derivatives. The cyclopropane-tethered iminium ion clearly served as a key intermediate in these reactions to trigger stereochemical outcomes, one of which was supported by a control experiment. (Figure presented.).
- Byeon, Huimyoung,Ryu, Sunghyeon,Yoo, Eun Jeong,Yang, Jung Woon
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supporting information
p. 5085 - 5091
(2021/09/20)
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- Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
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Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
- Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Gutiérrez-De-Terán, Hugo,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui
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p. 12938 - 12963
(2021/09/11)
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- Asymmetric Synthesis of Functionalized 9-Methyldecalins Using a Diphenylprolinol-Silyl-Ether-Mediated Domino Michael/Aldol Reaction
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Substituted 9-methyldecalin derivatives containing an all carbon quaternary chiral center were synthesized with excellent enantioselectivity via an organocatalyst-mediated domino reaction. The first reaction is a diphenylprolinol silyl ether-mediated Michael reaction, and the second reaction is an intramolecular aldol reaction. The enantiomerically pure catalyst is involved in both reactions.
- Hayashi, Yujiro,Salazar, Hugo A.,Koshino, Seitaro
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supporting information
p. 6654 - 6658
(2021/09/11)
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- Iron-Catalyzed ?±,?-Dehydrogenation of Carbonyl Compounds
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An iron-catalyzed α,β-dehydrogenation of carbonyl compounds was developed. A broad spectrum of carbonyls or analogues, such as aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to their α,β-unsaturated counterparts in a simple one-step reaction with high yields.
- Zhang, Xiao-Wei,Jiang, Guo-Qing,Lei, Shu-Hui,Shan, Xiang-Huan,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 1611 - 1615
(2021/03/03)
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- Method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and diphosphine ligand used in method
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The invention discloses a method for preparing olefine aldehyde by catalyzing terminal alkyne or terminal conjugated eneyne and a diphosphine ligand used in the method. According to the invention, indole-substituted phosphoramidite diphosphine ligand which is stable in air and insensitive to light is synthesized by utilizing a continuous one-pot method, and the indole-substituted phosphoramidite diphosphine ligand and a rhodium catalyst are used for jointly catalyzing to successfully achieve a hydroformylation reaction of aromatic terminal alkyne and terminal conjugated eneyne under the condition of synthesis gas for the first time, so that an olefine aldehyde structure compound can be rapidly and massively prepared, and particularly, a polyolefine aldehyde structure compound which is more difficult to synthesize in the prior art can be easily prepared and synthesized, and a novel method is provided for synthesis and modification of drug molecules, intermediates and chemical products.
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Paragraph 0133-0136
(2021/05/29)
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- Palladium-Catalyzed [5 + 2] Annulation of Vinylethylene Carbonates with Barbiturate-Derived Alkenes
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A palladium/XantPhos-catalyzed [5 + 2] annulation of VECs with electron-deficient alkenes having an isolated carbon-carbon double bond has been developed to afford spirobarbiturate-tetrahydrooxepines. This study provides an expedient assembly of biologically interesting spirobarbiturate-tetrahydrooxepines. The easy scalability and versatile transformability of the reaction products were also exhibited.
- Chen, Yuehua,Deng, Hao,Gao, Xing,Guo, Hongchao,Jiang, Feng,Wang, Wei,Wu, Yongjun,Zhu, Dongyu
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supporting information
p. 7158 - 7163
(2020/10/02)
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- Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
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We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
- Aleku, Godwin A.,Leys, David,Roberts, George W.
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p. 3927 - 3939
(2020/07/09)
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- Formation of Functional Cyclooctadiene Derivatives by Supramolecularly- Controlled Topochemical Reactions and Their Use as Highly Selective Fluorescent Biomolecule Probes?
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Controlling the regio- and stereochemistry of the photoproducts in solution is far more challenging for polyenes than for monoalkenes. Herein, a supramolecularly-controlled topochemical reaction of conjugated dienes in homogeneous system is developed, ultimately providing two cyclooctadiene-cored tetraimidazolium molecular receptors exclusively. These cyclooctadiene derivatives exhibited highly sensitive and selective fluorescence sensing for thymine relative to other biologically relevant species in aqueous solution at physiological pH. Both the cyclooctadiene moieties and imidazolium units play important roles in the selective recognition observed. The presented supramolecularly-controlled method allows the simple yet rare selective photoconversion of flexible cyclooctadiene derivatives in solution. This study offers a new synthetic strategy for the preparation of functional molecules with potential for use in biological applications.
- Gan, Ming-Ming,Han, Ying-Feng
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supporting information
p. 1040 - 1044
(2020/06/23)
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- Boosting multiple photo-assisted and temperature controlled reactions with a single redox-switchable catalyst: Solvents as internal substrates and reducing agent
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An alternative and economically viable process for the synthesis of β-aryl enals, enones and the aryl amines has been developed by partial oxidation of ethanol, isopropanol and N, N-dimethyl formamide (DMF). The formation of β-aryl enals, enones and the aryl amines was catalyzed by a mixed metal oxides layer of cobalt and chromium supported on halloysite nanotubes, designated as CoCr2O4-HNT. The C[sbnd]C and C[sbnd]N bond formation reactions were found to be influenced by temperature and the nature of base. The condensation of aldehyde with in situ generated acetaldehyde by ethanol oxidation forming β-aryl enals occurred selectively at 120 °C. The partial oxidation of isopropanol to acetone and its condensation with aldehydes forming β-aryl enones occurred at room temperature. Increase in temperature caused the liberation of hydrogen gas from isopropanol and allowed the reversible reduction of aldehydes to alcohols. Increase in temperature in isopropanol and increase in base concentration in ethanol causes the selective reduction of aldehydes to alcohols. Besides being active for the Claisen-Schmidt type of reactions and the aryl halides amination process, the synthesized catalyst was also found to be highly active for the photocatalytic oxidation of benzyl alcohols in absence of any external oxidizing agent. The positive holes (h+) generated at the Co(II) site as evident from EPR analysis was considered to be responsible for high photocatalytic activity of the material reducing the recombination rate of holes and electrons (e?). Density Functional Theory calculations were performed to understand the mechanism of ethanol oxidation to acetaldehyde.
- Bania, Kusum K.,Baruah, Manash J.,Bhattacharyya, Pradip K.,Das, Biraj,Karunakar, Galla V.,Roy, Subhasish,Saikia, Lakshi,Saikia, Pinku,Sharma, Mukesh
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p. 104 - 121
(2020/06/01)
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- Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells
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Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 μm) and PC3 (0.3 μm) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50=0.8 μm), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines.
- Meirelles, Matheus A.,Braga, Carolyne B.,Ornelas, Catia,Pilli, Ronaldo A.
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p. 1403 - 1417
(2019/08/01)
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- Phosphorous acid promoted isomerization of propargyl alcohols to α,β-unsaturated carbonyl compounds
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A metal-free and two-phase protocol for the Meyer-Schuster isomerization of propargyl alcohols to the corresponding α,β-unsaturated carbonyl compounds has been achieved in the presence of stoichiometric phosphorous acid aqueous solution, which produces the desired products in high yields with excellent stereoselectivity. Compared with the traditional methods, the procedure features broad scope of the substrates, mild conditions, and easy separation, providing an appealing alternative to the Meyer-Schuster reaction.
- Gan, Xiaotang,Fu, Zuqi,Liu,Yan, Yani,Chen, Chao,Zhou, Yongbo,Dong, Jianyu
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- Evolution of physical and photocatalytic properties of new Zn(II) and Ru(II) complexes
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Synthesis of Zn(II) and Ru(II) complexes were reported by using N4-macrocyclic Schiff base ligands under solvothermal conditions. The newly synthesized Zn(II) and Ru(II) complexes have been characterized by various physico-chemical techniques such as elemental analysis, molar conductance, HRMS, TGA, FESEM, UV–Vis, FT-IR, 1H NMR, and cyclic voltammetry. By using molar conductance studies, the complexes are formulated as [Zn(TPTTP)]Cl2 and [Ru(TPTTP)Cl2]. C–H bond activation of an sp3 group of methylstyrenes (converted into cinnamaldehydes) and C–H bond activation of the sp2 bond of polycyclic aromatic hydrocarbons through photooxidation was examined in the presence of Zn(II) and Ru(II) complexes. Reusable activity studies and photostability of catalyst are investigated by using UV–Vis spectra. Based on the results, higher catalytic activity of [Ru(TPTTP)Cl2] complex than [Zn(TPTTP)]Cl2 complex in both C–H bond activation and photooxidation of aromatic hydrocarbons has been reported.
- Gugulothu, Venkanna,Ahemed, Jakeer,Subburu, Mahesh,Yadagiri, Bhongiri,Mittal, Ritu,Prabhakar, Chetti,Pola, Someshwar
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p. 412 - 423
(2019/06/27)
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- Enantioselective Organocatalytic Enamine C?H Oxidation/Diels- Alder Reaction
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α,β-unsaturated aldehydes have been traditionally used in LUMO lowering asymmetric aminocatalysis (iminium catalysis), while the use of saturated aldehydes as substrates in this type of catalysis has been elusive, until recently. Herein, we demonstrate that organic, single-electron oxidants in the presence of diarylprolinol silylether type catalysts serve as effective tools for the transformation of electron rich enamines to iminium ions which partake in a subsequent Diels-Alder reaction. This enantioselective one-pot transformation represents the first example of saturated aldehydes being used in domino Diels-Alder reaction processes and demonstrates the power of this protocol for construction of stereo-defined chiral compounds and building blocks. (Figure presented.).
- D?ambaski, Zdravko,Tzaras, Dimitrios-Ioannis,Lee, Sunggi,Kokotos, Christoforos G.,Bondzic, Bojan P.
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supporting information
p. 1792 - 1797
(2019/02/25)
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- Highly γ-Regioselective 1,2-Addition of α,β-Unsaturated Oxime Ethers with Allylzinc Bromides: A Straightforward Approach for the Synthesis of Homoallylic Amines
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A highly regioselective reaction between allylzinc bromide reagents and α,β-unsaturated oxime ethers for the one-step synthesis of the homoallylic amines is reported. This process is a regioselective 1,2-addition reaction providing a new γ-position with carbon-carbon bond formation. Furthermore, the reaction substrates are widely applicable and can be produced in a high yield.
- Yang, Bo,Zhang, Songlin
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supporting information
p. 3736 - 3746
(2019/09/30)
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- Synthesis of Substituted β-Functionalised Styrenes by Microwave-Assisted Olefin Cross-Metathesis and Scalable Synthesis of Apremilast
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Preparation of diversely substituted β-functionalised styrenes by microwave-assisted olefin cross-metathesis (CM) is described. This method can be also employed in the synthesis of β-deuterated α,β-unsaturated sulfones from inexpensive allylbenzenes, though unprecedented one-pot isomerisation/deuteration/cross-metathesis sequence. One of such obtained CM products has been utilised in a new scalable synthesis of Apremilast (6), a potent and orally active phosphodiesterase 4 and tumour necrosis factor-α inhibitor. The same strategy was used in synthesis of an optical antipode of 6, ent-Apremilast.
- Jana, Anupam,Zieliński, Grzegorz Krzysztof,Czarnocka-?niada?a, Sylwia,Grudzień, Krzysztof,Podwysocka, Dominika,Szulc, Marcin,Kajetanowicz, Anna,Grela, Karol
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p. 5808 - 5813
(2019/11/03)
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- Pd-Au-Y as Efficient Catalyst for C-C Coupling Reactions, Benzylic C-H Bond Activation, and Oxidation of Ethanol for Synthesis of Cinnamaldehydes
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Pd-Au nanoalloy supported on zeolite-Y (Pd-Au-Y) matrix was found to be an effective catalyst for C-Cl bond activation and oxidative coupling of 2-naphthol, leading to the formation of various biaryl products and 1,1′-bi-2-naphthol, BINOL. The same catalyst was also highly efficient for selective oxidation of benzylic alcohols to benzaldehydes. Cinnamaldehydes were obtained directly from benzaldehydes by aldol condensation with acetaldehyde generated in situ by partial oxidation of ethanol in the presence of Pd-Au-Y catalyst at 120 °C under basic condition. The biaryl products were also obtained directly from benzylic alcohols in a one-pot system by reacting with phenylboronic acid. The formation of biaryls from benzylic alcohols was believed to occur via one-pot benzylic C-H and C-Cl bond activation. A high % yield of biaryls, BINOL, aldehydes, and cinnamaldehydes was obtained by performing different reactions using the single Pd-Au-Y catalyst. The strong interaction of chloro-benzylic alcohol was predominantly located at active gold species. X-ray photoelectron and diffuse reflectance spectroscopic studies revealed the strong interaction between Pd and Au particles. Electrochemical studies provided proper evidence for the individual role of the nanoparticles (NPs) in one-pot synthesis of biaryls from benzylic alcohols.
- Sharma, Mukesh,Das, Biraj,Baruah, Manash J.,Biswas, Subir,Roy, Subhasish,Hazarika, Anil,Bhargava, Suresh K.,Bania, Kusum K.
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p. 5860 - 5875
(2019/06/17)
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- Copper-catalyzed formylation of alkenyl C-H bonds using BrCHCl2 as a stoichiometric formylating reagent
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The first example of copper-catalyzed direct formylation of alkenyl C-H bonds for the facile synthesis of α,β-unsaturated aldehydes has been developed. This transformation has demonstrated high reactivity, mild reaction conditions and a broad substrate scope. BrCHCl2 is expected to be developed as an efficient stoichiometric C1 building block in organic synthesis.
- Bao, Yan,Wang, Gao-Yin,Zhang, Ya-Xuan,Bian, Kang-Jie,Wang, Xi-Sheng
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p. 2986 - 2990
(2018/03/23)
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- Palladium-catalyzed hydroformylation of terminal arylacetylenes with glyoxylic acid
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A simple, practical and governable palladium-catalyzed hydroformylation of terminal arylacetylenes has been disclosed. The reaction proceeds under syngas-free conditions, using readily available glyoxylic acid as the formyl source, under mild conditions, giving rise to a broad range of α,β-unsaturated aldehydes.
- Liu, Yang,Cai, Liangzhen,Xu, Sheng,Pu, Weiwen,Tao, Xiaochun
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supporting information
p. 2166 - 2168
(2018/03/06)
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- Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections
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Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.
- Wei, Hanwen,Mao, Fei,Ni, Shuaishuai,Chen, Feifei,Li, Baoli,Qiu, Xiaoxia,Hu, Linghao,Wang, Manjiong,Zheng, Xinyu,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 235 - 251
(2018/01/17)
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- Gold catalyzed Heck-coupling of arenediazonium o-benzenedisulfonimides
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Diazonium salts, and precisely arenediazonium o-benzenedisulfonimides, have been used for the first time as efficient electrophilic partners in gold catalyzed Heck-coupling reactions. The synthetic protocol was general, easy and gave the target products in satisfactory yields. Mechanistic insights revealed the fundamental roles of the o-benzenedisulfonimide anion as an electron transfer agent thath promotes a radical pathway that does not require the presence of photocatalysts or external oxidants.
- Barbero, Margherita,Dughera, Stefano
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p. 295 - 301
(2018/01/12)
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- Hendrickson reagent induced rearrangement of aryl propargyl alcohols to α,β-unsaturated aldehydes
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The Hendrickson reagent (triphenylphosphonium anhydride trifluoromethanesulfonate), prepared from the reaction of triphenylphosphine oxide (Ph3PO) and triflic anhydride (Tf2O) (2:1 stoichiometry), promotes dehydrations and various coupling reactions. The reagent has been used to transform oximes to nitriles and to prepare esters, amides and many other functional groups through the intermediacy of an alkoxyphosphonium salt. The reagent proved useful in heterocycle synthesis of thiazolines, imidazolines, quinoline precursors, isoquinolines, β-carbolines, phenanthridines, 11H-indolo[3,2-c]quinolines, quinoline-lactones, furoquinolinones, and indolizino[1,2-b]quinolin-9(11H)-ones. Moreover, the reagent has been key to the successful total synthesis of several natural products. Aryl propargyl alcohols with a terminal α-acetylenic group undergo rapid conversion to the corresponding α,β-unsaturated aldehydes at room temperature in dichloromethane in the presence of one equivalent of triphenylphosphonium anhydride trifluoromethanesulfonate. The reaction involved adding freshly distilled Tf2O (1.0 mmol) to a solution of Ph3PO (2.0 mmol) in CH2Cl2 (10 mL) at 0oC under N2 atmosphere. After stirring for 10 min, the propargyl alcohol (1.0 mmol) was added as a CH2Cl2 solution (2 mL), followed by the addition of water and Et3N (2.0 mmol) and further stirring at room temperature for 1h. Subsequent workup with 5% NaHCO3 (20 mL) and purification afforded α,β-unsaturated aldehydes. Eighteen aryl propargyl alcohol substrates with a terminal α-acetylenic group were transformed in good to excellent yields (71-85%) to enals. The methodology proved successful with secondary and tertiary alcohols with stereoselectivity favouring exclusively the E isomer. All the synthesized compounds are known and were characterized (1H,13C, and M.P) and compared to literature values. The method offers several advantages such as exclusive stereoselectivity, short reaction time, good yield, mild reaction conditions, and simple operational procedure.
- Moussa, Ziad,Aljuhani, Ateyatallah
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p. 845 - 853
(2018/11/06)
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- Highly Enantioselective Synthesis of Alkylpyridine Derivatives through a Michael/Michael/Aldol Cascade Reaction
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A method for the synthesis of pyridine derivatives based on a triple cascade reaction catalyzed by chiral secondary amines was developed. The resulting cyclohexenes (three C–C bonds were formed) were obtained in good yields with good diastereoselectivities and excellent enantioselectivities.
- Meazza, Marta,Potter, Michael,Pitak, Mateusz B.,Coles, Simon J.,Mazzanti, Andrea,Rios, Ramon
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supporting information
p. 719 - 725
(2017/02/05)
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- Synthesis of Aldehydes by Organocatalytic Formylation Reactions of Boronic Acids with Glyoxylic Acid
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Reported herein is a conceptually novel organocatalytic strategy for the formylation of boronic acids. New reactivity is engineered into the α-amino-acid-forming Petasis reaction occurring between aryl boronic acids, amines, and glyoxylic acids to prepare aldehydes. The operational simplicity of the process and its ability to generate structurally diverse and valued aryl, heteroaryl, and α,β-unsaturated aldehydes containing a wide array of functional groups, demonstrates the practical utility of the new synthetic strategy.
- Huang, He,Yu, Chenguang,Li, Xiangmin,Zhang, Yongqiang,Zhang, Yueteng,Chen, Xiaobei,Mariano, Patrick S.,Xie, Hexin,Wang, Wei
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supporting information
p. 8201 - 8205
(2017/06/30)
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- New Class of Anion-Accelerated Amino-Cope Rearrangements as Gateway to Diverse Chiral Structures
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We report useful new lithium-assisted asymmetric anion-accelerated amino-Cope rearrangement cascades. A strategic nitrogen atom chiral auxiliary serves three critical roles, by (1) enabling in situ assembly of the chiral 3-amino-1,5-diene precursor, (2) facilitating the rearrangement via a lithium enolate chelate, and (3) imparting its influence on consecutive inter- or intramolecular C-C or C-X bond-forming events via resulting chiral enamide intermediates or imine products. The mechanism of the amino-Cope rearrangement was explored with density functional theory. A stepwise dissociation-recombination mechanism was found to be favored. The stereochemistry of the chiral auxiliary determines the stereochemistry of the Cope product by influencing the orientation of the lithium dienolate and sulfinylimine fragments in the recombination step. These robust asymmetric anion-accelerated amino-Cope enabled cascades open the door for rapid and predictable assembly of complex chiral acyclic and cyclic nitrogen-containing motifs in one pot.
- Chogii, Isaac,Das, Pradipta,Fell, Jason S.,Scott, Kevin A.,Crawford, Mark N.,Houk,Njardarson, Jon T.
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p. 13141 - 13146
(2017/09/26)
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- One-Pot l-Proline-Mediated Stereoselective α-C(sp2)–H Fluorination of α,β-Unsaturated Aldehydes through Methoxyfluorination–Elimination
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A one-pot, two-step l-proline-mediated stereoselective α-C(sp2)–H fluorination of α,β-unsaturated aldehydes towards their corresponding (Z)-α-fluoro-α,β-unsaturated aldehydes has been developed. The first step utilises Selectfluor as a fluorinating agent in CH3NO2/MeOH forming (Z)-α-fluoro-α,β-unsaturated aldehydes and their corresponding dimethyl acetals through methoxyfluorination-elimination. In the second step, water is added to promote the hydrolytic cleavage of the dimethyl acetals. The obtained (Z)-α-fluoro-α,β-unsaturated aldehydes were smoothly reduced to the corresponding alcohols by using NaBH4.
- Zhou, Jiadi,Jiang, Xinpeng,Jin, Can,Guo, Zhicheng,Su, Bin,Su, Weike
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supporting information
p. 3631 - 3634
(2017/07/22)
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- Metal- and Acid-Free Methyl Triflate Catalyzed Meyer-Schuster Rearrangement
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A novel metal- and acid-free preparation of synthetically useful α,β-unsaturated carbonyl compounds from propargyl alcohols has been realized. This Meyer-Schuster rearrangement process is effectively catalyzed by methyl triflate (20 mol%) to prepare a broad scope of conjugated E -enals and E -enones generally in good to excellent yields (up to 90%). This reaction procedure operates under mild conditions (70 °C), in air, with short reaction times (1 h). Moreover, a carbocation intermediate trapped by the solvent 2,2,2-trifluoroethanol was isolated during this transformation.
- Yang, Lu,Zeng, Qingle
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p. 3149 - 3156
(2017/07/12)
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- Isomerization of 3-unsubstituted 4,5-dihydroisoxazoles over alumina. A new synthesis of β-hydroxy nitriles
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3-Unsubstituted 4,5-dihydroisoxazoles obtained by nitrosation of arylcyclopropanes are capable of undergoing efficient isomerization into 3-aryl-3-hydroxypropanenitriles during chromatography on alumina.
- Mochalov,Fedotov,Trofimova,Gazzaeva,Zefirov
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p. 397 - 403
(2016/06/13)
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- One-Pot Synthesis of (S)-Baclofen via Aldol Condensation of Acetaldehyde with Diphenylprolinol Silyl Ether Mediated Asymmetric Michael Reaction as a Key Step
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An efficient asymmetric total synthesis of (S)-baclofen was accomplished via a one-pot operation from commercially available materials using sequential reactions, such as aldol condensation of acetaldehyde, diphenylprolinol silyl ether mediated asymmetric Michael reaction of nitromethane, Kraus-Pinnick oxidation, and Raney Ni reduction. Highly enantioenriched baclofen was obtained in one pot with a good yield over four reactions.
- Hayashi, Yujiro,Sakamoto, Daisuke,Okamura, Daichi
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supporting information
p. 4 - 7
(2016/01/15)
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- Oxygenative and Dehydrogenative [3 + 3] Benzannulation Reactions of α,β-Unsaturated Aldehydes and γ-Phosphonyl Crotonates Mediated by Air: Regioselective Synthesis of 4-Hydroxybiaryl-2-carboxylates
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Regioselective synthesis of 4-hydroxybiphenyl-2-carboxylates via the base-mediated oxygenative [3 + 3] benzannulation reaction of α,β-unsaturated aldehydes and γ-phosphonyl crotonates is reported. A hydroxyl group is installed in the final product on the originally phosphorus-bound carbon via a novel oxygenative and dehydrogenative transformation. The reaction proceeds rapidly in an open flask, uses atmospheric oxygen as an oxidant, and affords good yields of substituted biaryl phenols. (Chemical Equation Presented).
- Joshi, Prabhakar Ramchandra,Nanubolu, Jagadeesh Babu,Menon, Rajeev S.
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supporting information
p. 752 - 755
(2016/03/01)
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- Highly efficient Au hollow nanosphere catalyzed chemo-selective oxidation of alcohols
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Micelles of poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) (PS-PVP-PEO) with core-shell-corona structures have been used as a scaffold for the fabrication of gold (Au) hollow nanospheres of particle size 26 ± 2 nm using HAuCl4 and NaBH4 as metal precursor and reducing agent, respectively. The PS core acts as a template for hollow void, the PVP shell serves as reaction sites for inorganic precursors, and PEO corona stabilizes the composite particles. Under acidic conditions, the PVP shell domain becomes positively charged pyridinum-species that electrostatically interacts with negatively charged AuCl4- ions. On reduction of these composite particles and subsequent solvent extraction leads to the formation of Au hollow nanospheres. Various analytical tools such as powder X-ray diffraction (XRD), transmission electron microscope (TEM), thermogravimetric analyses (TG/DTA), dynamic light scattering of (DLS) have been employed to characterize the polymeric micelles and hollow nanoparticles. The TEM and XRD studies confirmed the formation of highly crystalline Au hollow nanospheres. The Au hollow nanosphere/H2O2 system efficiently catalyzes the chemoselective oxidation of allylic-type unsaturated alcohols into aldehydes and ketones under mild liquid-phase conditions. The versatility of present catalytic system for the oxidation of other substrates like aliphatic-, acylic-, aromatic-, and heteroaromatic alcohols to their respective keto compounds has also been reported.
- Sasidharan, Manickam,Anandhakumar, Sundaramurthy,Bhanja, Piyali,Bhaumik, Asim
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- Stereoselective organocatalytic oxidation of alcohols to enals: A homologation method to prepare polyenes
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A novel method for organocatalytic oxidation through oxidative enamine catalysis was developed with excellent compatibility for the direct syntheses of enals from simple saturated alcohols. By using this amine-catalyzed IBX-oxidation, a wide range of aromatic and aliphatic substituted enals were successfully generated in high yields and exclusively stereoselective E-geometry. Moreover, varying the solvents and/or the loading amounts of IBX allowed for the selective oxidation of alcohols and aldehydes. Importantly, the homologous application of this method provided a selective and efficient way of preparing various highly sensitive conjugated polyene frameworks, which are enriched in natural products.
- Chen, Xiaobei,Zhang, Yinan,Wan, Huixin,Wang, Wei,Zhang, Shilei
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p. 3532 - 3535
(2016/03/04)
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- Traceless Rhodium-Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of β-Aryl Ketones
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A one-pot three-step sequence involving Rh-catalyzed alkene hydroacylation, sulfide elimination and Rh-catalyzed aryl boronic acid conjugate addition gave products of traceless chelation-controlled hydroacylation employing alkyl aldehydes. The stereodefined β-aryl ketones were obtained in good yields with excellent control of enantioselectivity. Good variation of all three reaction components is possible.
- Bouisseau, Ana?s,Gao, Ming,Willis, Michael C.
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supporting information
p. 15624 - 15628
(2016/10/25)
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- An enantioselective three-component reaction of diazoacetates with indoles and enals by iridium/iminium co-catalysis
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The first example of chiral secondary amine and iridium(i) co-catalyzed enantioselective three-component reaction of aryldiazoacetates, indoles and enals was rationally designed and developed to afford 3-substituted indole derivatives in good yields and with moderate diastereoselectivity as well as excellent enantioselectivity. This reaction is proposed to proceed through the enantioselective trapping of iridium(i)-associated zwitterionic intermediates via selective 1,4-addtition to the chiral amine activated enals.
- Li, Mingfeng,Guo, Xin,Jin, Weifeng,Zheng, Qing,Liu, Shunying,Hu, Wenhao
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supporting information
p. 2736 - 2739
(2016/02/19)
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- RADIOACTIVE IODINE LABELED STYRYL SUBSTITUTED AROMATIC HETEROCYCLIC COMPOUND
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PROBLEM TO BE SOLVED: To provide a novel tau protein imaging agent that allows imaging of biological tau protein by a noninvasive, nuclear medical method. SOLUTION: The present invention provides a radioactive iodine labeled styryl substituted aromatic heterocyclic compound represented by a predetermined general formula or a salt thereof, or a radioactive medicine comprising the same. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0039
(2016/11/21)
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- Oxidative cleavage of allyl ethers by an oxoammonium salt
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A method to oxidatively cleave allyl ethers to their corresponding aldehydes mediated by an oxoammonium salt is described. Using a biphasic solvent system and mild heating, cleavage proceeds readily, furnishing a variety of α,β-unsaturated aldehydes and ketones.
- Kelly, Christopher B.,Ovian, John M.,Cywar, Robin M.,Gosselin, Taylor R.,Wiles, Rebecca J.,Leadbeater, Nicholas E.
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supporting information
p. 4255 - 4259
(2015/04/14)
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- Wittig Reactions of Trialkylphosphine-derived Ylides: New Directions and Applications in Organic Synthesis
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The development of semi-stabilized, stabilized, and functionalized ylides derived from short-chain trialkylphosphines in the Wittig-type olefination reactions toward the synthesis of alkenes, including stilbenes, styrenes, and 1,3-dienes, as well as reagents for homologation reactions, are described. The methods allow easy access to alkenes with high (E)-stereoselectivity in good yield. These reactions are conducted with weak bases in aqueous media, which allows easy separation of water-soluble phosphine oxides. The development of a mild organocatalytic process for the Wittig reaction and extension toward the preparation of reporter stilbenes under biological conditions are also described. Applications toward the preparation of biologically active natural products and derivatives are discussed.
- McNulty, James,McLeod, David,Das, Priyabrata,Zepeda-Velázquez, Carlos
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p. 619 - 632
(2016/01/15)
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- Highly regio- And enantioselective synthesis of g,d-unsaturated amido esters by catalytic hydrogenation of conjugated enamides
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An efficient and highly regio- and enantioselective catalytic asymmetric hydrogenation of a,γ-dienamido esters to g,d-unsaturated amido esters has been achieved using Rh/ TangPhos as the catalyst. A series of γ,δ-unsaturated amido acids were furnished in excellent yields with up to 99%ee. This effective methodology was applied in the asymmetric synthesis of key intermediate of Ramipril, an ACE inhibitor.
- Min, Gao,Jing-jing, Meng,Hui, Lv,Xumu, Zhang
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supporting information
p. 1885 - 1887
(2015/02/19)
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- A metal-free one-pot cascade synthesis of highly functionalized biaryl-2-carbaldehydes
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A metal-free one-pot cascade annulation of acyclic substrates dienaminodioate, cinnamaldehydes and allyl amine was achieved for the synthesis of polyfunctional biaryl-2-carbaldehydes. The reaction proceeds at room temperature by a trifluoroacetic acid mediated Diels-Alder pathway. Synthetic applications of the resulting biaryl-2-carbaldehyde have been demonstrated by conversion into an array of diverse molecules with biological and materials chemistry relevance. The present work offers a complementary route to the existing metal mediated cross-coupling methods for the preparation of biaryls.
- Challa, Chandrasekhar,Vellekkatt, Jamsheena,Ravindran, Jaice,Lankalapalli, Ravi S.
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supporting information
p. 8588 - 8592
(2014/12/11)
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- Proline-catalyzed asymmetric Diels-Alder reactions of an o-quinodimethane
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Catalytic asymmetric Diels-Alder reaction of α-amino-o-quinodimethane with α,β-unsaturated aldehydes was achieved with high diastereo- and enantioselectivities in the presence of l-proline, which acts as a promoter to generate the quinodimethane from the corresponding precursor as well as a chiral catalyst for the enantioselective Diels-Alder reaction.
- Shirakawa, Hidenori,Sano, Hiroshi
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p. 4095 - 4097
(2014/07/22)
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- An efficient partial reduction of α,β-unsaturated esters using DIBAL-H in flow
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The partial reduction of α,β-unsaturated esters and benzoate derivatives to form the corresponding aldehydes was achieved using a flow reactor system within 1 s at a high flow rate (18 mL min-1) under cryogenic conditions (-97°C). Commercially available diisobutylaluminium hydride (DIBAL-H) was used as the reductant. The desired enals and benzaldehyde derivatives, except for 4-methoxycinnamate and 4-methoxybenzoate, were formed selectively and redox economically in moderate to high yields.
- Yoshida, Masahito,Otaka, Hiroyuki,Doi, Takayuki
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p. 6010 - 6016
(2015/03/30)
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- Synergistic catalysis: Enantioselective addition of Alkylbenzoxazoles to Enals
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A novel catalytic enantioselective methodology based on synergistic catalysis is reported. The strategy involves: 1) the metal-Lewis-acid activation of alkylazaarenes, and 2) the secondary-amine activation of enals. Consequently, highly functionalized chiral alkylazaarenes were obtained in good yields and with reasonable stereoselectivity.
- Meazza, Marta,Ceban, Victor,Pitak, Mateusz B.,Coles, Simon J.,Rios, Ramon
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supporting information
p. 16853 - 16857
(2015/01/09)
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- A mononuclear copper(ii) complex immobilized in mesoporous silica: An efficient heterogeneous catalyst for the aerobic oxidation of benzylic alcohols
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The diamide ligand 2,6-bis[(N-phenyl)amido]-4-methylphenol (HL) has been used to synthesize a mononuclear copper(ii) complex, [CuL2(DMF) 2] (1). The X-ray crystal structure of this complex reveals that the copper(ii) center is coordi
- Samanta, Suvendu,Das, Sudipto,Samanta, Partha Kumar,Dutta, Supriya,Biswas, Papu
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p. 19455 - 19466
(2013/10/22)
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- Development of a robust reagent for the two-carbon homologation of aldehydes to (E)-α,β-unsaturated aldehydes in water
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Synthesis of a new pinacolacetal-phosphonium salt and its reaction with aldehydes to give homologated acetals and two-carbon homologated unsaturated aldehydes is presented. The chemistry takes place in water under mild conditions and the sequence can be performed in one-flask operation.
- Mcnulty, James,Zepeda-Velazquez, Carlos,McLeod, David
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supporting information
p. 3146 - 3149
(2013/11/06)
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