- Catalytic Asymmetric Construction of Tertiary Carbon Centers Featuring an α-Difluoromethyl Group with CF2H-CH2-NH2as the "building Block"
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We report here for the first time a novel difluoromethylated ketimine building block condensed by thioisatin and difluoroethylamine, offering efficient access to a broad range of enantioenriched products bearing difluoroethylamine units (27 examples, ≤98% yield, >99% ee) in the presence of quinine-derived squaramide. Further transformation of the intermediate would generate a variety of versatile functional blocks like α-difluoromethyl amines, β-amino acid, and β-diamine with retention of the enantiomeric excess at the difluoromethyl-bound carbon.
- Gao, Fengyun,Guo, Yifei,Sun, Mengmeng,Wang, Yalan,Yang, Changyan,Wang, Yuqiang,Wang, Kairong,Yan, Wenjin
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supporting information
p. 2584 - 2589
(2021/04/13)
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- Dipolar HCP materials as alternatives to DMF solvent for azide-based synthesis
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Hypercrosslinked polymers HCP-DMF and HCP-DMF-SO3H containing abundant and flexible DMF moieties were designed and synthesized. Benefitting from the solvation microenvironment provided by the pseudo-DMF moities, the polar HCPs manifested outstanding performances in the conversions of NaN3 to benzylic azides and 1,2,3-triazoles in EtOH (95%), respectively, avoiding the use of risky DMF and improving the separation processes of the products.
- Bai, Rongxian,Gao, Feng,Gu, Yanlong,Li, Minghao
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supporting information
p. 7499 - 7505
(2021/10/12)
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- Four-Step Domino Reaction Enables Fully Controlled Non-Statistical Synthesis of Hexaarylbenzene with Six Different Aryl Groups**
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Hexaarylbenzene (HAB) derivatives are versatile aromatic systems playing a significant role as chromophores, liquid crystalline materials, molecular receptors, molecular-scale devices, organic light-emitting diodes and candidates for organic electronics. Statistical synthesis of simple symmetrical HABs is known via cyclotrimerization or Diels–Alder reactions. By contrast, the synthesis of more complex, asymmetrical systems, and without involvement of statistical steps, remains an unsolved problem. Here we present a generally applicable synthetic strategy to access asymmetrical HAB via an atom-economical and high-yielding metal-free four-step domino reaction using nitrostyrenes and α,α-dicyanoolefins as easily available starting materials. Resulting domino product—functionalized triarylbenzene (TAB)—can be used as a key starting compound to furnish asymmetrically substituted hexaarylbenzenes in high overall yield and without involvement of statistical steps. This straightforward domino process represents a distinct approach to create diverse and still unexplored HAB scaffolds, containing six different aromatic rings around central benzene core.
- Dill, Maximilian,Grau, Benedikt W.,Hampel, Frank,Jux, Norbert,Kahnt, Axel,Tsogoeva, Svetlana B.
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supporting information
p. 22307 - 22314
(2021/08/25)
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- Exploiting the chiral ligands of bis(Imidazolinyl)-and bis(oxazolinyl)thiophenes—Synthesis and application in Cu-catalyzed friedel–crafts asymmetric alkylation
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Five new C2-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The util-ity of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subse-quently, the optimized tridentate ligand L5 and Cu(OTf)2 catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for the asymmetric induction of the Friedel–Crafts asymmetric alkylation.
- Al-Majid, Abdullah Mohammed,Alammari, Abdullah Saleh,Alshahrani, Saeed,Barakat, Assem,Haukka, Matti,Islam, Mohammad Shahidul
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- PYRROLIDINE COMPOUNDS FOR THE TREATMENT OF MALARIA
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Pyrrolidine derivatives of formula I are used as anti-malaria agents, wherein the variables are as defined herein. Method of employing such agents in the treatment and prevention of malaria are also provided herein.
- -
-
Page/Page column 30; 31
(2020/06/19)
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- Ionic-Liquid Controlled Nitration of Double Bond: Highly Selective Synthesis of Nitrostyrenes and Benzonitriles
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Unprecedented in literature, the conversion of aryl alkenes into β-nitrostyrenes (2) or benzonitriles (3) with sodium nitrite can be governed by an appropriate choice of ionic liquid (IL) medium. A general trend was found for the selectivity of these processes, which depends on the nature of IL, with imidazolium-based ILs, such as [Bmim]Cl, that favor the C–H nitration leading to β-nitrostyrenes, while tetraalkylammonium-based ILs, such as TBAA, privilege the C=C bond cleavage affording benzonitriles. Besides a substrate scope, mechanistic hypotheses were provided on the origin of the different selectivity in the two kinds of ILs, based on their own tunable properties such as polarity, viscosity, and solvent cage effects.
- Casiello, Michele,Caputo, Daniela,Fusco, Caterina,Cotugno, Pietro,Rizzi, Vito,Dell'Anna, Maria Michela,D'Accolti, Lucia,Nacci, Angelo
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supporting information
p. 6012 - 6018
(2020/08/24)
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- Geometrically Selective Denitrative Trifluoromethylthiolation of β-Nitrostyrenes with AgSCF3for (E)-Vinyl Trifluoromethyl Thioethers
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An efficient copper(II)-promoted denitrative trifluoromethylthiolation under mild reaction conditions has been developed for vinyl trifluoromethyl thioethers to construct Cvinyl-SCF3 bonds with stable AgSCF3 as a source of the trifluoromethylthio. This reaction system tolerates a broad range of functional groups to commendably achieve a high product yield and excellent stereoselectivity of E/Z.
- Fang, Ge,Hong, Jianquan,Huang, Shuai,Jiang, Chao,Liu, Yang,Zhang, Wei,Zheng, Changge
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supporting information
(2020/07/03)
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- Biological evaluation and SAR analysis of novel covalent inhibitors against fructose-1,6-bisphosphatase
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Fructose-1,6-bisphosphatase (FBPase) is an attractive target for affecting the GNG pathway. In our previous study, the C128 site of FBPase has been identified as a new allosteric site, where several nitrovinyl compounds can bind to inhibit FBPase activity. Herein, a series of nitrostyrene derivatives were further synthesized, and their inhibitory activities against FBPase were investigated in vitro. Most of the prepared nitrostyrene compounds exhibit potent FBPase inhibition (IC50 3, CF3, OH, COOH, or 2-nitrovinyl were installed at the R2 (meta-) position of the benzene ring, the FBPase inhibitory activities of the resulting compounds increased 4.5–55 folds compared to those compounds with the same groups at the R1 (para-) position. In addition, the preferred substituents at the R3 position were Cl or Br, thus compound HS36 exhibited the most potent inhibitory activity (IC50 = 0.15 μM). The molecular docking and site-directed mutation suggest that C128 and N125 are essential for the binding of HS36 and FBPase, which is consistent with the C128-N125-S123 allosteric inhibition mechanism. The reaction enthalpy calculations show that the order of the reactions of compounds with thiol groups at the R3 position is Cl > H > CH3. CoMSIA analysis is consistent with our proposed binding mode. The effect of compounds HS12 and HS36 on glucose production in primary mouse hepatocytes were further evaluated, showing that the inhibition was 71% and 41% at 100 μM, respectively.
- Chen, Haifeng,Guo, Yanrong,Han, Xinya,Hu, Wei,Huang, Yunyuan,Ren, Yanliang,Tang, Zilong,Wang, Qi,Wei, Lin,Xia, Qinfei,Yan, Jufen
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supporting information
(2020/07/23)
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- Molecular Engineering of β-Substituted Oxoporphyrinogens for Hydrogen-Bond Donor Catalysis
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A new class of bifunctional hydrogen-bond donor organocatalyst using oxoporphyrinogens having increased intramolecular hydrogen-bond donor distances is reported. Oxoporphyrinogens are highly non-planar rigid macrocycles containing a multiple hydrogen bond-forming binding site. In this work, we describe the first example of non-planar OxPs as hydrogen-bond donor catalysts prepared using a molecular engineering approach of the binding site for dual activation of substrates. The introduction of β-substituents is key to the catalytic activity and the catalysts are able to catalyze 1,4-conjugate additions and sulfa-Michael additions, as well as, Henry and aza-Henry reactions at low catalyst loadings (≤ 1 mol-%) under mild conditions. Preliminary mechanistic studies have been carried out and a possible reaction mechanism has been proposed based on the bi-functional activation of both substrates through hydrogen-bonding interactions.
- Chahal, Mandeep K.,Payne, Daniel T.,Matsushita, Yoshitaka,Labuta, Jan,Ariga, Katsuhiko,Hill, Jonathan P.
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supporting information
p. 82 - 90
(2020/01/02)
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- A photocatalyst-free photo-induced denitroalkylation of β-nitrostyrenes with 4-alkyl substituted Hantzsch esters at room temperature
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A photocatalyst-free stereoselectively photo-induced strategy for the denitroalkylation of β-nitrostyrenes using 4-alkyl substituted Hantzsch esters as the alkyl source under xenon lamp irradiation is developed. The reaction proceeds at room temperature and affords the corresponding products in moderate to excellent yields. The oxidant di-t-butyl peroxide serves as an efficient radical initiator under irradiation of a Xenon lamp, initiating alkyl radicals from the 4-alkyl substituted Hantzsch esters.
- Duan, Chunying,Hao, Xinyu,Jin, Kun,Li, Yaming,Wang, Jiaao,Zhang, Rong,Zhang, Siyu
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supporting information
(2020/02/18)
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- Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling
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Nitroalkanes react specifically with aldehydes, providing rapid, stable, and chemoselective protein bioconjugation. These nitroalkylated proteins mimic key post-translational modifications (PTMs) of proteins and can be used to understand the role of these
- Adebomi, Victor,Mahesh, Sriram,Muneeswaran, Zilma P.,Raj, Monika
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supporting information
p. 2793 - 2801
(2020/01/25)
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- One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes
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β-Nitrostyrenes underwent a Diels-Alder reaction with Danishefsky's diene to afford cyclohexenes together with the corresponding hydrolyzed products, 3-arylated-5-methoxy-4-nitrocyclohexanones. When the reaction was conducted in the presence of water, the cyclohexenes were efficiently hydrolyzed into cyclohexanones. Subsequent aromatization by heating the cyclohexanone with a catalytic amount of iodine in dimethyl sulfoxide gave 3-arylated-4-nitrophenols. The reaction of nitrostyrenes with Danishefsky's diene could be conducted in one pot to directly afford the corresponding nitrophenols. Moreover, a heteroaryl group, e.g., a thienyl group could be introduced into the nitrophenol framework.
- Asahara, Haruyasu,Hiraishi, Minami,Nishiwaki, Nagatoshi
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p. 1830 - 1836
(2020/09/15)
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- Metal-free, room temperature, acid-K2S2O8 mediated method for the nitration of olefins: An easy approach for the synthesis of nitroolefins
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Here, we have developed a simple, room temperature method for the nitration of olefins by using inexpensive sodium nitrite as a source of nitro groups in the presence of trifluoroacetic acid (TFA) and potassium persulfate (K2S2O8) under an open atmosphere. Styrenes and mono-substituted olefins give stereo-selective corresponding E-nitroolefins under optimized conditions, however, 1,1-bisubstituted olefins give a mixture of E- and Z-nitroolefins. The optimized conditions work well with electron-donating, electron-withdrawing, un-substituted and heterocyclic styrenes and mono-substituted olefins and give corresponding nitroolefins with good to excellent yields.
- Ambala, Srinivas,Singh, Rohit,Singh, Maninder,Cham, Pankaj Singh,Gupta, Ria,Munagala, Gurunadham,Yempalla, Kushalava Reddy,Vishwakarma, Ram A.,Singh, Parvinder Pal
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p. 30428 - 30431
(2019/10/04)
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- 4-Aryl Pyrrolidines as Novel Orally Efficacious Antimalarial Agents. Part 2: 2-Aryl- N-(4-arylpyrrolidin-3-yl)acetamides
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Malaria is caused by infection from the Plasmodium parasite and kills hundreds of thousands of people every year. Emergence of new drug resistant strains of Plasmodium demands identification of new drugs with novel chemotypes and mechanisms of action. As
- Meyers, Marvin J.,Liu, Jianguang,Liu, Zhijun,Ma, Hongwei,Dai, Linglin,Adah, Dickson,Zhao, Siting,Li, Xiaofen,Liu, Xiaorong,Lu, Yongzhi,Huang, Yanhui,Tu, Zhengchao,Chen, Xiaoping,Tortorella, Micky D.
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supporting information
p. 966 - 971
(2019/06/17)
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- Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design
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A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, A12, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure-activity relationship of compound A12, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Akt1 and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.
- Dong, Xiaowu,Zhan, Wenhu,Zhao, Mengting,Che, Jinxin,Dai, Xiaoyang,Wu, Yizhe,Xu, Lei,Zhou, Yubo,Zhao, Yanmei,Tian, Tian,Cheng, Gang,Jin, Zegao,Li, Jia,Shao, Yanfei,He, Qiaojun,Yang, Bo,Weng, Qinjie,Hu, Yongzhou
-
supporting information
p. 7264 - 7288
(2019/08/20)
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- NHC-Catalyzed Dual Stetter Reaction: A Mild Cascade Annulation for the Syntheses of Naphthoquinones, Isoflavanones, and Sugar-Based Chiral Analogues
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The N-heterocycle carbene (NHC)-catalyzed dual Stetter cascade reaction is discovered through coupling of β-nitrostyrene with phthalaldehyde under mild conditions to furnish valuable aryl-naphthoquinones. The generality of the new reaction is validated through the development of a C-C and O-C bond forming Stetter cascade reaction using salicylaldehydes to obtain functionalized dihydroisoflavanones. The mild NHC organocatalysis is successfully employed for the construction of optically pure sugar-based naphthoquinones and dihydroisoflavanones. Herein, NHC is found as a unique and powerful organocatalyst to construct homoatomic C-C cross-coupling, heteroatomic O-C bond formation, and cascade cyclization utilizing NO2 as a leaving group at ambient temperature. A mechanistic pathway of the new metal-free catalysis is predicted on the basis of our ESI-MS study of the ongoing reaction and literature.
- Mitra, Rajendra N.,Show, Krishanu,Barman, Debabrata,Sarkar, Satinath,Maiti, Dilip K.
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- Comprehensive evaluation of antioxidant effects of Japanese Kampo medicines led to identification of Tsudosan formulation as a potent antioxidant agent
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Oxidative stress due to the overproduction of reactive oxygen species plays an important role in the pathogenesis of various diseases. In the present study, we comprehensively evaluated the antioxidant activities of 147 oral formulations of Japanese traditional herbal medicines (Kampo medicines), representing the entire panel of oral Kampo medicines listed in the Japanese National Health Insurance Drug List, using in vitro radical scavenging assays, including the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity assay, the superoxide anion scavenging activity assay, and the oxygen radical absorption capacity assay. Three of the formulations tested, namely, Tsudosan, Daisaikoto, and Masiningan, showed the most potent in vitro antioxidant activities and were selected for further investigation of their intracellular and in vivo antioxidant effects. The results of the 2′,7′-dichlorodihydrofluorescin diacetate assay demonstrated that all three Kampo medicines significantly inhibited hydrogen peroxide-induced oxidative stress in human hepatocellular liver carcinoma HepG2 cells. In addition, Tsudosan significantly increased the serum biological antioxidant potential values when orally administrated to mice, indicating that it also had in vivo antioxidant activity. The potent antioxidant activity of Tsudosan may be one of the mechanisms closely correlated to its clinical usage against blood stasis.
- Sato, Naoko,Li, Wei,Takemoto, Hiroaki,Takeuchi, Mio,Nakamura, Ai,Tokura, Emi,Akahane, Chie,Ueno, Kanako,Komatsu, Kana,Kuriyama, Noriko,Onoda, Toshihisa,Higai, Koji,Koike, Kazuo
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p. 163 - 172
(2018/11/06)
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- Facile Synthesis of 1,3,5-Triarylbenzenes and 4-Aryl-NH-1,2,3-Triazoles Using Mesoporous Pd-MCM-41 as Reusable Catalyst
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We report mesoporous nano-Pd-MCM-41 catalyzed rapid and efficient synthesis of 1,3,5-triarylbenzenes via de-nitrative cyclotrimerization of β-nitrostyrenes. All the reactions were very fast and high yielding. The Pd-MCM-41 was also very effective in catalyzing de-nitrative [3+2] cycloaddition of β-nitrostyrenes with TMSN3 to synthesize 4-aryl-NH-1,2,3-triazoles. The catalyst was reused at least up to eight times with minimum loss of catalytic activity.
- Saha, Arijit,Wu, Chia-Ming,Peng, Rui,Koodali, Ranjit,Banerjee, Subhash
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p. 104 - 111
(2019/01/04)
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- Access to C5-Alkylated Indolines/Indoles via Michael-Type Friedel-Crafts Alkylation Using Aryl-Nitroolefins
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A straightforward synthetic route toward C5-alkylated indolines/indoles has been developed. The strategy is composed of Zn(OTf)2-catalyzed Friedel-Crafts alkylation of N-benzylindolines with nitroolefins, and a series of diverse indolines was first obtained in up to 99% yield. This reaction provides a direct and practical route to a variety of the C5-alkylated indolines which were also utilized for accessing corresponding indoles. Indoline derivatives with free NH groups could be obtained through an N-deprotection reaction. Moreover, the primary alkyl nitro groups in both indolines and indoles are amenable to further synthetic elaborations, thereby broadening the diversity of the products.
- Ertugrul, Berrak,Kilic, Haydar,Lafzi, Farrokh,Saracoglu, Nurullah
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p. 9018 - 9038
(2018/06/27)
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- Base-catalyzed reactions enhanced by solid acids: Amine-catalyzed nitroaldol (Henry) reactions enhanced by silica gel or mesoporous silica SBA-15
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The reactions of various aldehydes with CH3NO2 catalyzed by Et3N, n-C6H13NH2, and Me2N(CH2)2NH2 were accelerated by the addition of silica gel to give aromatic (aliphatic) β-nitroalcohols, aromatic nitroalkenes, and aromatic 1,3-dinitroalkanes, respectively. Mesoporous silica SBA-15 showed higher activity than silica gel for the synthesis of aromatic nitroalkenes by the reactions of the corresponding aldehydes with CH3NO2 catalyzed by n-C6H13NH2.
- Tanemura, Kiyoshi,Suzuki, Tsuneo
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supporting information
p. 392 - 396
(2017/12/28)
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- One-Step, Effective, and Cascade Syntheses of Highly Functionalized Cyclopentenes with High Diastereoselectivity
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Tetrabutylammonium fluoride works as an effective organocatalyst for the cycloaddition between phenacylmalononitriles and electron-deficient olefins (having substituent groups of NO2, CHO, and COR), providing a facile synthetic route to versatile multifunctionalized cyclopentenes having an allylic quaternary carbon center bearing both cyano and carboxamide groups with high yields and high diastereoselectivity. Preliminary studies reveal that these functionalized cyclopentenes are convenient precursors for making α-cyano-functionalized cyclopentadienone oximes.
- Alishetty, Suman,Shih, Hong-Pin,Han, Chien-Chung
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p. 2513 - 2516
(2018/05/17)
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- Highly Enantioselective Michael Addition of Dithiomalonates to Nitroolefins Catalyzed by New Bifunctional Chiral Thioureas
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We report a highly efficient asymmetric Michael addition of dithiomalonates to trans -β-nitroole?ns catalyzed by versatile cinchona-based bifunctional thioureas, which provides the corresponding adducts in high yields (up to 92%) and with excellent enanti
- Yuan, Jia-Ni,Liu, Hui-Xia,Tian, Qin-Qin,Ji, Nan,Shen, Kuo,He, Wei
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supporting information
p. 2577 - 2586
(2018/05/03)
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- Identification of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamate-nitrostyrene hybrid as potent antiproliferative and apoptotic inducing agent against cervical cancer cell lines
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The present study seeks to describe the design and synthesis of six new Michael adducts of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamate with nitrostyrenes and their in vitro antiproliferative activity against human cervical cancer cell lines [HeLa (HPV 18 positive), CaSki (HPV 16 positive) and ViBo (HPV negative) cervical cancer cell lines]. Virtual screening of the physicochemical properties of all compounds have also been presented. All the compounds exploited significant antiproliferative activity on the three cervical cancer cell lines. Compound 8a was found to be most potent, displaying in vitro antiproliferative activity against HeLa, CaSki and ViBo cervical cancer cell lines superior to Cisplatin and Paclitaxel with IC50 values 0.99 ± 0.007, 2.36 ± 0.016 and 0.73 ± 0.002 μM respectively. In addition, compound 8a did not trigger the necrosis cell death to the test cancer cell lines. Further mechanistic study revealed that compound 8a could inhibit the cancer cell proliferation by inducing apoptosis through caspase-3 activation. Moreover, cell cycle analysis indicated that compound 8a could arrest the cell cycle at the G1 phase for HeLa and CaSki cancer cells. At the predetermined IC50 values on cancer cells, compound 8a did not induce any necrotic (cytotoxic) death to the normal human lymphocytes. In the present design, (1S,4S)-2,5-diazabicyclo[2.2.1]heptane system was found to be superior than the piperazine counterpart 11.
- Laskar, Sujay,Sánchez-Sánchez, Luis,Flores, Sebastián M.,López-Mu?oz, Hugo,Escobar-Sánchez, María L.,López-Ortiz, Manuel,Hernández-Rodríguez, Marcos,Regla, Ignacio
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p. 621 - 635
(2018/02/09)
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- Fe(III)/Pyridine-Mediated Decarboxylative Nitration of α,β-Unsaturated Acids with Iron Nitrate
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A novel and efficient method for the synthesis of (E)-nitroolefins in moderate to excellent yields is developed by Fe(III)/pyridine-mediated decarboxylative nitration of α,β-unsaturated acids with iron nitrate. A series of α,β-unsaturated acids are well tolerated in this procedure.
- Yang, Zan,Li, Jiao,Hua, Jie,Yang, Tao,Yi, Jianmin,Zhou, Congshan
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supporting information
p. 1079 - 1082
(2017/05/19)
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- Chloro/bromotrimethylsilane-Cu(NO3)2·3H2O: Safe and efficient reagent system for the decarboxylative ipso-nitration and dibromination of cinnamic acids
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Further synthetic potential of halotrimethylsilane-nitrate salt mixture is revealed. A mixture of TMSX-Cu(NO3)2·3H2O system is found to be an efficient reagent system for both the decarboxylative nitration (ipso-nitration) when X?=?Cl, and dibromination of cinnamic acids, with X?=?Br, under mild conditions. The reactions are safe and simple, affording the corresponding products (E)-β-nitrostyrenes, and anti-2,3-dibromo-3-phenylpropanoic acids in high yields with high selectivity in a relatively short time. Use of hazardous and toxic nitrating systems such as acetyl nitrate and brominating agents such as molecular bromine can be avoided.
- Roshandel, Sahar,Gurung, Laxman,Mathew, Thomas,Prakash, G.K. Surya
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supporting information
p. 2842 - 2845
(2017/06/27)
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- Catalyst-free sulfa-Michael addition of pyrimidine-2-thiol to nitroolefins
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Catalyst-free sulfa-Michael addition of pyrimidine-2-thiol to nitroolefins is described. A series of 2-((2-nitro-1-arylethyl)thio)pyrimidines were efficiently synthesized. The protocol has advantages of wide range of substituents tolerance, no catalyst, additives and bases, mild condition, and high yield. The method can also extend to gram scale.
- Li, Zheng,Song, Geyang,He, Jiaojiao,Du, Yan,Yang, Jingya
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p. 686 - 698
(2017/09/06)
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- Continuous-flow synthesis using a column reactor packed with heterogeneous catalysts: A convenient production of nitroolefins by using amino-functionalized silicagel
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A continuous-flow synthesis of β-nitroolefins by using heterogeneous base catalysts has been developed. Although the use of an excess amount of nitro-donor such as nitromethane is required in conventional methods, nearly equimolar amounts of nitro-donors and carbonyl compounds are sufficient for high-yielding production of nitroolefins. Catalysts for this flow protocol are inexpensive and abundant, and high durability and high productivity were also realized by using an appropriate second support.
- Ishitani, Haruro,Furiya, Yuichi,Kobayashi, Shū
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supporting information
p. 6229 - 6232
(2017/09/30)
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- Cu(NO3)2-catalyzed nitrodecarboxylation of α,β-unsaturated acids: facile synthesis of (E)-nitroolefins under additive-free conditions
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Abstract: An additive-free, facile, efficient, and ecofriendly protocol for synthesis of (E)-nitroolefins via nitrodecarboxylation of α,β-unsaturated acids has been developed. Cu(NO3)2 was used as both nitrating agent and catalyst. Furthermore, the presented methodology offers several advantages such as easily accessible and stable substrates, inexpensive catalyst, high to excellent yield, short reaction time, and simple posttreatment procedure. Graphical Abstract: [Figure not available: see fulltext.]
- Luo, Zai-Gang,Xu, Feng,Fang, Yu-Yu,Liu, Peng,Xu, Xue-Mei,Feng, Cheng-Tao,Li, Zhong,He, Jie
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p. 6079 - 6087
(2016/06/01)
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- Synthesis and biological evaluation of novel inhibitors against 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea
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1,3,8-Trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of β-nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (50 = 0.29 μM). In particular, some of these compounds had moderate fungicidal activity against Magnaporthe grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50 = 9.5 ppm). Furthermore, compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that β-nitrostyrene derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast.
- Chen, Haifeng,Han, Xinya,Qin, Nian,Wei, Lin,Yang, Yue,Rao, Li,Chi, Bo,Feng, Lingling,Ren, Yanliang,Wan, Jian
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p. 1225 - 1230
(2016/03/01)
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- Iron-Mediated One-Pot Synthesis of 3,5-Diarylpyridines from β-Nitrostyrenes
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An operationally simple and mild one-pot protocol for the synthesis of a variety of 3,5-diarylpyridines from β-nitrostyrenes was achieved by using elemental iron. This reaction proceeds via reduction of the nitro group, resulting in in situ imine formation followed by trimolecular condensation with concomitant debenzylative aromatization. By employing this method, a series of symmetrical and unsymmetrical 3,5-diarylpyridines were synthesized with good to excellent yields. In addition, this method was also utilized for the synthesis of Sch-21418, an anti-inflammatory agent on gram scale.
- Sathish, Manda,Chetna, Jadala,Hari Krishna, Namballa,Shankaraiah, Nagula,Alarifi, Abdullah,Kamal, Ahmed
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p. 2159 - 2165
(2016/03/15)
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- Organocatalytic Enantioselective Transfer Hydrogenation of β-Amino Nitroolefins
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The asymmetric organocatalytic transfer hydrogenation of β-acylamino and β-tert-butyloxycarbonylamino nitroolefins has been successfully realised in excellent enantioselectivities and yields (up to >99% ee, 97% yield) with a simple thiourea catalyst and a Hantzsch ester as hydrogen source, giving a direct access to enantiomerically pure β-amino nitroalkanes. (Figure presented.).
- Ferraro, Antonino,Bernardi, Luca,Fochi, Mariafrancesca
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supporting information
p. 1561 - 1565
(2016/10/13)
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- Yolk-shell-structured mesoporous silica: A bifunctional catalyst for nitroaldol-Michael one-pot cascade reaction
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Great interest in heterogeneous asymmetric catalysis has focused on obtaining an enantioselective cascade reaction through a controllable active site-isolated heterogeneous catalyst. Herein, we utilize a yolk-shell-structured mesoporous silica and assemble an active site-isolated bifunctional heterogeneous catalyst, where chiral cinchonine-based squaramide molecules are anchored within a silicate channel as an outer shell while amine-functionalities are entrapped onto a silicate yolk as an inner core. Structural analyses and characterizations of the heterogeneous catalyst reveal its well-defined single-site chiral active species within its silicate network. Electron microscopy confirms the yolk-shell-structured mesoporous material. As presented in this study, as a bifunctional heterogeneous catalyst, it enables an efficiently nitroaldol-Michael cascade reaction to conduct the three-component coupling of nitromethane, aldehyde and acetylacetone into various chiral diones with high yields and up to 99% enantioselectivities in a one-pot process. As expected, this active site-isolated catalyst not only enhances the catalytic selectivity of the first-step nitroaldol condensation, but also keeps the enantioselectivity of the second-step Michael addition. Moreover, the heterogeneous catalyst can be also recovered easily and recycled repeatedly, making it an interesting feature in a three-component organic transformation.
- An, Juzeng,Cheng, Tanyu,Xiong, Xi,Wu, Liang,Han, Bin,Liu, Guohua
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p. 5714 - 5720
(2016/07/21)
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- Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies
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This paper describes a facile protocol, efficient, and environmentally benign for the synthesis a series of barbiturate acid substituted at C5 position 3a–o. The desired compounds subjected in vitro for different set of bioassays including against anti-oxidant (DPPH and super oxide scavenger assays), anti-cancer, α-glucosidase and β-glucuronidase inhibitions. Compound 3m (IC50?=?22.9?±?0.5?μM) found to be potent α-glucosidase enzyme inhibitors and showed more activity than standard acarbose (IC50?=?841?±?1.73?μM). Compound 3f (IC50?=?86.9?±?4.33?μM) found to be moderate β-Glucuronidase enzyme inhibitors and showed activity comparatively less than the standard D-saccharic acid 1,4-lactone (IC50?=?45.75?±?2.16?μM). Furthermore, in sillico investigation was carried out to investigate bonding mode of barbiturate acid derivatives.
- Barakat, Assem,Islam, Mohammad Shahidul,Al-Majid, Abdullah Mohammed,Ghabbour, Hazem A.,Yousuf, Sammer,Ashraf, Mahwish,Shaikh, Nimra Naveed,Iqbal Choudhary,Khalil, Ruqaiya,Ul-Haq, Zaheer
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supporting information
p. 72 - 79
(2016/07/26)
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- Straightforward synthesis of 1,2-dicyanoalkanes from nitroalkenes and silyl cyanide mediated by tetrabutylammonium fluoride
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A straightforward synthesis of 1,2-dicyanoalkanes by reacting nitroalkenes with trimethylsilyl cyanide in the presence of tetrabutylammonium fluoride is described. The reaction proceeds through a tandem double Michael addition under mild conditions. Employing the hypervalent silicate generated from trimethylsilyl cyanide and tetrabutylammonium fluoride is essential for achieving this transformation. Mechanistic studies suggest that a small amount of water included in the reaction media plays a key role. This protocol is applicable to various types of substrates including electron-rich and electron-deficient aromatic nitroalkenes, and aliphatic nitroalkenes. Moreover, vinyl sulfones were found to be good alternatives, particularly for electron-deficient nitroalkenes. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 1,2-dicyanoalkanes.
- Kiyokawa, Kensuke,Nagata, Takaya,Hayakawa, Junpei,Minakata, Satoshi
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supporting information
p. 1280 - 1285
(2015/02/19)
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- Diastereoselective synthesis of polysubstituted cyclopentanols and cyclopentenes containing stereogenic centers via domino Michael/cyclization reaction
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A highly efficient domino Michael/cyclization reaction was developed for the synthesis of cyclopentanols and cyclopentenes with four and three stereogenic centers that were generated in one-pot reaction conditions with high diastereoselectivity. The reactions proceeded through a one-pot three-component reaction of β-nitrostyrenes, malononitrile and phenacyl bromide derivatives in basic media at room temperature.
- Ahadi,Naghdiani,Balalaie,Rominger
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p. 6860 - 6866
(2015/08/24)
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- Stereoselective reaction of 2-carboxythioesters-1,3-dithiane with nitroalkenes: An organocatalytic strategy for the asymmetric addition of a glyoxylate anion equivalent
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An efficient organocatalytic methodology has been developed to perform the stereoselective addition of 2-carboxythioesters-1,3-dithiane to nitroalkenes. Under mild reaction conditions γ-nitro-β-aryl-α-keto esters with up to 92% ee were obtained, realizing a formal catalytic stereoselective conjugate addition of the glyoxylate anion synthon. The reaction products are versatile starting materials for further synthetic transformations; for example, the simultaneous reduction of the nitro group and removal of the dithiane ring was accomplished, allowing the preparation of a GABAB receptor agonist baclofen.
- Massolo, Elisabetta,Benaglia, Maurizio,Genoni, Andrea,Annunziata, Rita,Celentano, Giuseppe,Gaggero, Nicoletta
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p. 5591 - 5596
(2015/05/27)
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- Asymmetric Michael addition of α-fluoro-α-nitroalkanes to nitroolefins: Facile preparation of fluorinated amines and tetrahydropyrimidines
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An asymmetric Michael addition of α-fluoro-α-nitroalkanes to nitroolefins was developed, and the products were obtained in good chemical yields and with high stereoselectivities. Highly functionalized adducts provided ready access to fluorinated amines and tetrahydropyrimidines in an optically enriched form.
- Kwiatkowski, Jacek,Lu, Yixin
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supporting information
p. 9313 - 9316
(2014/08/05)
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- Highly efficient iridium-catalyzed asymmetric hydrogenation of β-acylamino nitroolefins
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The first highly efficient Ir-catalyzed enantioselective hydrogenation of β-acylamino nitroolefins is reported. This reaction provides straightforward access to chiral β-amino nitroalkanes in high yields and excellent enantioselectivities (up to >99.9% ee) catalyzed by an Ir-(R,R)-f-spiroPhos complex. This journal is
- Yan, Qiaozhi,Liu, Man,Kong, Duanyang,Zi, Guofu,Hou, Guohua
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supporting information
p. 12870 - 12872
(2014/12/11)
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- 17a-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Paragraph 0213
(2014/03/21)
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- Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
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A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
- Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
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p. 6713 - 6716
(2013/10/01)
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- Enantioselective nickel-catalyzed michael additions of 2-acetylazaarenes to nitroalkenes
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2-Acetylazaarenes undergo catalytic enantioselective Michael additions to nitroalkenes in the presence of a chiral Ni(II)-bis(oxazoline) complex. The process is tolerant of a range of azines or azoles in the pronucleophilic component, resulting in Michael products in moderate to high enantioselectivities.
- Simpson, Alain J.,Lam, Hon Wai
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supporting information
p. 2586 - 2589
(2013/07/26)
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- What controls regiochemistry in 1,3-dipolar cycloadditions of Muenchnones with nitrostyrenes?
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The distinct experimentally observed regiochemistries of the reactions between mesoionic muenchnones and β-nitrostyrenes or phenylacetylene are shown by DFT/BDA/ETS-NOCV analyses of the transition states to be dominated by steric and reactant reorganization factors, rather than the orbital overlap considerations predicted by Frontier Molecular Orbital (FMO) Theory.
- Lopchuk, Justin M.,Hughes, Russell P.,Gribble, Gordon W.
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supporting information
p. 5218 - 5221
(2013/11/06)
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- A novel route to organonitrites by Pd-catalyzed cross-coupling of sodium nitrite and potassium organotrifluoroborates
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Microwave irradiated palladium-catalyzed cross-coupling reaction of potassium styryltrifluoroborates and sodium nitrite gives the corresponding styryl nitrites in high yields. Potassium aryltrifluoroborates also furnish aryl nitrites under same reaction condition. This unprecedented cross-coupling is an interesting development and has the potential to lead to new nitration protocols.
- Al-Masum, Mohammad,Saleh, Nabil,Islam, Tasfia
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supporting information
p. 1141 - 1144
(2013/03/28)
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- Urea postmodified in a metal-organic framework as a catalytically active hydrogen-bond-donating heterogeneous catalyst
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New functionally diverse urea-derived MOF hydrogen-bond-donating heterogeneous catalysts were achieved via postsynthetic modification, which exhibit excellent catalytic activity and very broad substrate scopes for the Friedel-Crafts alkylation reactions.
- Dong, Xiao-Wu,Liu, Tao,Hu, Yong-Zhou,Liu, Xin-Yuan,Che, Chi-Ming
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supporting information
p. 7681 - 7683
(2013/09/02)
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- Catalyst-free and solvent-free Michael addition of 1,3-dicarbonyl compounds to nitroalkenes by a grinding method
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An environmentally benign, fast and convenient protocol has been developed for the Michael addition of 1,3-dicarbonyl compounds to β-nitroalkenes in good to excellent yields by a grinding method under catalyst- and solvent-free conditions.
- Xie, Zong-Bo,Wang, Na,Wu, Ming-Yu,He, Ting,Le, Zhang-Gao,Yu, Xiao-Qi
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supporting information; experimental part
p. 534 - 538
(2012/06/29)
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- 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Page/Page column 40-41
(2012/04/04)
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- Cascade formation of isoxazoles: Facile base-mediated rearrangement of substituted oxetanes
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Give me five! Nitro compounds and oxetan-3-one react through an intriguing cascade sequence to give isoxazole-4-carbaldehydes using inexpensive reagents in a one-pot procedure (see scheme; Ms=methanesulfonyl). A variety of 3-substituted isoxazole-4-carbaldehydes were obtained in high overall yields.
- Burkhard, Johannes A.,Tchitchanov, Boris H.,Carreira, Erick M.
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supporting information; experimental part
p. 5379 - 5382
(2011/07/08)
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- Straightforward synthesis of nitroolefins by microwave- or ultrasound-assisted Henry reaction
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β-Nitroalcohol or nitroethylene derivatives can be obtained from aryl aldehydes and nitromethane under Henry condensation conditions. We present a new modification using microwave irradiation or ultrasound as the energy source. Microwave irradiation allowed a novel one-pot synthesis of nitroolefins from aryl aldehydes using ammonium acetate as a catalyst without solvent. Different reaction conditions, such as base, solvent, and reaction time were studied. Only small amounts of β-hydroxyl nitro compounds were isolated, using microwave irradiation for less than 25 min. In contrast, the use of ultrasound increased the yield of the nitroalcohols.
- Rodríguez, Jose M.,Dolors Pujol
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experimental part
p. 2629 - 2632
(2011/06/10)
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- An efficient, transition-metal-free process for the synthesis of substituted dihydrofurans via a Michael/cyclization tandem reaction
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An efficient green route for the synthesis of substituted dihydrofurans was developed through a simple base-catalyzed, tandem reaction of nitrostyrene with 1,3-dicarbonyl compounds. The desired products were prepared with a large substrate scope and in excellent yields (up to 95%).
- Wu, Ming-Yu,Wang, Ming-Qi,Li, Kun,Feng, Xing-Wen,He, Ting,Wang, Na,Yu, Xiao-Qi
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supporting information; experimental part
p. 679 - 683
(2011/03/21)
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- A novel enzymatic tandem process: Utilization of biocatalytic promiscuity for high stereoselective synthesis of 5-hydroxyimino-4,5-dihydrofurans
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A lipase-catalyzed protocol for the synthesis of 5-hydroxyimino-4,5- dihydrofurans via tandem coupling between β-nitrostyrenes and 1,3-dicarbonyl compounds was developed in a 'one-pot' strategy. A series of β-nitrostyrenes were employed to expand the scope of this new biocatalytic promiscuity with high stereoselectivity (Z/E up to 99:1) and moderate to good yields. The reaction activity of 1,3-cyclohexanedione was found to be better than linear 2,4-pentanedione, while ethyl acetoacetate and diethylmalonate were not suitable for this reaction under the same conditions. Single-crystal X-ray diffraction analysis indicated that the reaction was stereoselective and Z-stereomer was found to be the major product. A reaction mechanism was supposed to elucidate the biocatalytic process.
- Wu, Ming-Yu,Li, Kun,He, Ting,Feng, Xing-Wen,Wang, Na,Wang, Xiao-Yan,Yu, Xiao-Qi
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experimental part
p. 2681 - 2688
(2011/04/23)
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