- Novel 4,5-dihydrospiro[benzo[c]azepine-1,1′-cyclohexan]-3(2H)-one derivatives as PARP-1 inhibitors: Design, synthesis and biological evaluation
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To further explore the research of novel PARP-1 inhibitors, we designed and synthesized a series of novel amide PARP-1 inhibitors based on our previous research. Most compounds displayed certain antitumor activities against four tumor cell lines (A549, HepG2, HCT-116, and MCF-7). Specifically, the candidate compound R8e possessed strong anti-proliferative potency toward A549 cells with the IC50 value of 2.01 μM. Compound R8e had low toxicity to lung cancer cell line. And the in vitro enzyme inhibitory activity of compound R8e was better than rucaparib. Molecular docking studies provided a rational binding model of compound R8e in complex with rucaparib. The following cell cycle and apoptosis assays revealed that compound R8e could arrest cell cycle in the S phase and induce cell apoptosis. Western blot analysis further showed that compound R8e could effectively inhibit the PAR's biosynthesis and was more effective than rucaparib. Overall, based on the biological activity evaluation, compound R8e could be a potential lead compound for further developing novel amide PARP-1 inhibitors.
- Li, Shuai,Li, Xin-yang,Zhang, Ting-jian,Zhu, Ju,Liu, Kai-li,Wang, De-pu,Meng, Fan-hao
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- Design, synthesis and biological evaluation of homoerythrina alkaloid derivatives bearing a triazole moiety as PARP-1 inhibitors and as potential antitumor drugs
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A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 μM), which was higher than harringtonine (IC50 = 10.55 μM), pemetrexed (IC50 = 3.39 μM), and rucaparib (IC50 = 4.91 μM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.
- Li, Shuai,Li, Xin-yang,Zhang, Ting-jian,Kamara, Mohamed Olounfeh,Liang, Jing-wei,Zhu, Ju,Meng, Fan-hao
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- Conjugated copper(II) porphyrin polymer and N-hydroxyphthalimide as effective catalysts for selective oxidation of cyclohexylbenzene
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A nanomaterial catalyst of azo-bridged Cu(II) porphyrin polymer (CuII-APP) was synthesized and characterized by scanning electron microscopy, transmission electron microscopy and N2adsorption measurement. CuII-APP had a nanoporous structure, with the particle size of about 30?nm. Owing to the special structure, CuII-APP acted as an efficient heterogeneous catalyst for selective oxidation of cyclohexylbenzene into cyclohexylbenzene-1-hydroperoxide. When N-hydroxyphthalimide was used as co-catalyst, this binary catalyst system showed an obvious synergic effect. After being recovered and reused, CuII-APP and NHPI still had high catalytic activities.
- Tan, Zhiwei,Zhu, Junhui,Yang, Weijun
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- Reactions of diaryliodonium trifluoromethanesulfonates with low-valent ytterbium and samarium reagents
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The reduction of diaryliodonium trifluoromethanesulfonates with low-valent ytterbium and samarium reagents has been studied. In the reaction of diphenyliodonium trifluoromethanesulfonate with two equimolar amounts of metallic ytterbium, benzene is formed
- Makioka, Yoshikazu,Fujiwara, Yuzo,Kitamura, Tsugio
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- Polymer supported naphthalene-catalysed sodium reactions
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Arene-catalysed sodium reactions have been utilised in the generation of organosodium complexes, from a variety of organochloride complexes, in high yield. Phenyltrimethylsilane, benzene and 2-methyl-1-phenyl-1-propanol were prepared in yields >80%, using polymer supported naphthalene-catalysed sodium reactions, whereby phenylsodium, prepared from the reaction of chlorobenzene, sodium powder and polymer-supported naphthalene (5-100%), was quenched with chlorotrimethylsilane, water or PriCHO respectively. The Royal Society of Chemistry.
- Van Den Ancker, Tania R.,Love, Cameron J.
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- Enantioselective Nickel-Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution
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The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α-N-chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.
- Liu, En-Chih,Topczewski, Joseph J.
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supporting information
p. 5308 - 5313
(2021/05/04)
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- Hydrogen-Catalyzed Acid Transformation for the Hydration of Alkenes and Epoxy Alkanes over Co-N Frustrated Lewis Pair Surfaces
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Hydrogen (H2) is widely used as a reductant for many hydrogenation reactions; however, it has not been recognized as a catalyst for the acid transformation of active sites on solid surface. Here, we report the H2-promoted hydration of alkenes (such as styrenes and cyclic alkenes) and epoxy alkanes over single-atom Co-dispersed nitrogen-doped carbon (Co-NC) via a transformation mechanism of acid-base sites. Specifically, the specific catalytic activity and selectivity of Co-NC are superior to those of classical solid acids (acidic zeolites and resins) per micromole of acid, whereas the hydration catalysis does not take place under a nitrogen atmosphere. Detailed investigations indicate that H2 can be heterolyzed on the Co-N bond to form Hδ-Co-N-Hδ+ and then be converted into OHδ-Co-N-Hδ+ accompanied by H2 generation via a H2O-mediated path, which significantly reduces the activation energy for hydration reactions. This work not only provides a novel catalytic method for hydration reactions but also removes the conceptual barriers between hydrogenation and acid catalysis.
- Deng, Qiang,Deng, Shuguang,Gao, Ruijie,Li, Xiang,Tsang, Shik Chi Edman,Wang, Jun,Zeng, Zheling,Zou, Ji-Jun
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p. 21294 - 21301
(2021/12/17)
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- Palladium-Aminopyridine Catalyzed C?H Oxygenation: Probing the Nature of Metal Based Oxidant
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A mechanistic study of direct selective oxidation of benzylic C(sp3)?H groups with peracetic acid, catalyzed by palladium complexes with tripodal amino-tris(pyriylmethyl) ligands, is presented. The oxidation of arylalkanes having secondary and tertiary benzylic C?H groups, predominantly yields, depending on the substrate and conditions, either the corresponding ketones or alcohols. One of the three 2-pyriylmethyl moieties, which is pending in the starting catalyst, apparently, facilitates the active species formation and takes part in stabilization of the high-valent Pd center in the active species, occupying the axial coordination site of palladium. The catalytic, as well as isotopic labeling experiments, in combination with ESI-MS data and DFT calculations, point out palladium oxyl species as possible catalytically active sites, operating essentially via C?H abstraction/oxygen rebound pathway. For the ketones formation, O?H abstraction/в-scission mechanism has been proposed.
- Lubov, Dmitry P.,Bryliakova, Anna A.,Samsonenko, Denis G.,Sheven, Dmitriy G.,Talsi, Evgenii P.,Bryliakov, Konstantin P.
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p. 5109 - 5120
(2021/11/10)
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- Deciphering Reactivity and Selectivity Patterns in Aliphatic C-H Bond Oxygenation of Cyclopentane and Cyclohexane Derivatives
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A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and tert-butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs. With cyclohexanes, the relative importance of HAT from C-1 decreases on going from methyl- and phenylcyclohexane to ethyl-, isopropyl-, and tert-butylcyclohexane. Deactivation is also observed at C-2 with site-selectivity that progressively shifts to C-3 and C-4 with increasing substituent steric bulk. The site-selectivities observed in the corresponding oxidations promoted by ethyl(trifluoromethyl)dioxirane support this mechanistic picture. Comparison of these results with those obtained previously for C-H bond azidation and functionalizations promoted by the PINO radical of phenyl and tert-butylcyclohexane, together with new calculations, provides a mechanistic framework for understanding C-H bond functionalization of cycloalkanes. The nature of the HAT reagent, C-H bond strengths, and torsional effects are important determinants of site-selectivity, with the latter effects that play a major role in the reactions of oxygen-centered HAT reagents with monosubstituted cyclohexanes.
- Martin, Teo,Galeotti, Marco,Salamone, Michela,Liu, Fengjiao,Yu, Yanmin,Duan, Meng,Houk,Bietti, Massimo
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supporting information
p. 9925 - 9937
(2021/06/30)
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- Spiro [benzo [c] aza-1, 1 '-cyclohexyl]-3-ketone compound
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The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and particularly relates to a 4, 5-dihydrospiro [benzo [c] aza-1, 1 '-cyclohexyl]-3 (2H)-ketone compound as well as a preparation method and application of the 4, 5-dihydrospiro [benzo [c] aza-1, 1'-cyclohexyl]-3 (2H)-ketone compound. The structural general formula of the compound is shown in the specification, wherein an R group on an a benzene ring is substituted by a 2-position, 3-position or 4-position monosubstituted fluorine atom, methyl, chlorine atom, methoxyl, bromine atom or hydrogen atom. Pharmacological studies show that the compound provided by the invention has certain inhibitory activity on human colon cancer HCT-116 cells, can be used for preparing antitumor drugs, and opens up a new way for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.
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Paragraph 0050-0052
(2021/06/12)
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- Copper-Catalyzed Enantioselective Hydroalkoxylation of Alkenols for the Synthesis of Cyclic Ethers
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The copper-catalyzed enantioselective intramolecular hydroalkoxylation of unactivated alkenes for the synthesis of tetrahydrofurans, phthalans, isochromans, and morpholines from 4- and 5-alkenols is reported. The substrate scope is complementary to existing enantioselective alkene hydroalkoxylations and is broad with respect to substrate backbone and alkene substitution. The asymmetric induction and isotopic labeling studies support a polar/radical mechanism involving enantioselective oxycupration followed by C-[Cu] homolysis and hydrogen atom transfer. Synthesis of the antifungal insecticide furametpyr was accomplished.
- Chen, Dake,Berhane, Ilyas A.,Chemler, Sherry R.
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supporting information
p. 7409 - 7414
(2020/06/29)
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- Iodobenzene-catalyzed oxidative cleavage of olefins to carbonyl compounds
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A metal-free approach for the oxidative cleavage of carbon–carbon double bonds of olefins to carbonyl compounds was established by using oxidant m-CPBA and non-metallic organocatalyst PhI in toluene/H2O. A broad scope of aromatic olefins was used. All the reactions proceeded smoothly at 35 °C in short reaction time to furnish the respective mono- and double carbonyl compounds selectively in moderate to good yields.
- Du, Lele,Wang, Zechao,Wu, Junliang
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supporting information
(2020/07/20)
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- Visible-light-promoted site-specific and diverse functionalization of a c(sp3)-c(sp3) bond adjacent to an arene
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We report here a strategy for inert C-C bond functionalization. Site-specific cleavage and functionalization of a saturated C(sp3)-C(sp3) bond via a visible-light-induced radical process have been achieved. The general features of this reaction are as follows. (1) Both linear and cyclic C(sp3)-C(sp3) bonds with a vicinal arene can be specifically functionalized. (2) One carbon is converted into a ketone, and another can be tunably converted into nitrile, peroxide, or halide. (3) The typical conditions include 1.0 mol % of Ru(bpy)3Cl2, 1.0 or 5.0 equiv of Zhdankin reagent, white CFL (24 W), open flask, and room temperature. These reactions offer powerful tools to modify carbon skeletons that are intractable by conventional methods. Good selectivity and functional group tolerance, together with mild and open air conditions, make these transformations valuable and attractive.
- Fang, Fang,Liu, Zhong-Quan,Sun, Minzhi,Wang, Nengyong,Wang, Yaxin,You, Huichao,Zhao, Jianyou
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p. 6603 - 6612
(2020/07/27)
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- A General Method for Photocatalytic Decarboxylative Hydroxylation of Carboxylic Acids
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A general and practical method for decarboxylative hydroxylation of carboxylic acids was developed through visible light-induced photocatalysis using molecular oxygen as the green oxidant. The addition of NaBH4 to in situ reduce the unstable peroxyl radical intermediate much broadened the substrate scope. Different sp3 carbon-bearing carboxylic acids were successfully employed as substrates, including phenylacetic acid-type substrates, as well as aliphatic carboxylic acids. This transformation worked smoothly on primary, secondary, and tertiary carboxylic acids.
- Khan, Shah Nawaz,Zaman, Muhammad Kashif,Li, Ruining,Sun, Zhankui
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p. 5019 - 5026
(2020/05/01)
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- Design, synthesis and biological evaluation of erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors
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Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.
- Li, Shuai,Li, Xin-yang,Meng, Fan-hao,Qian, Xin-hua,Xue, Wen-han,Zhang, Ting-jian,Zhu, Ju
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supporting information
(2020/01/21)
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- 1-azaspiro[5.5]undecyl-3-one and 1-azaspiro[5.5]undecyl-3-alcohol compounds
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The invention belongs to the technical field of medicines, and particularly relates to 1-azaspiro[5.5]undecyl-3-one and 1-azaspiro[5.5]undecyl-3-alcohol compounds and a preparation method and application thereof. The general formulas of the 1-azaspiro[5.5]undecyl-3-one compound and the 1-azaspiro[5.5]undecyl-3-alcohol compounds are shown in a formula I and a formula II in the specification. A six-membered spiro structure is synthesized for the first time, a brand-new compound with a better anti-tumor effect is obtained, and pharmacological research shows that the compound has certain inhibitory activity on human colon cancer HCT-116 cells. The preparation method of the 1-azaspiro[5.5]undecyl-3-one compound and the 1-azaspiro[5.5]undecyl-3-alcohol compound is simple and feasible, the yieldis relatively good, and the method is suitable for industrial production.
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Paragraph 0078-0080
(2020/05/30)
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- Photochemical Flow Oximation of Alkanes
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The nitrosation of several alkanes using tert-butyl nitrite has been performed in flow showing a remarkable reduction in the reaction time compared with batch processing. Due to the necessity for large excesses of the alkane component a continuous recycling process was devised for the preparation of larger quantities of material.
- Griffiths, Oliver M.,Ruggeri, Michele,Baxendale, Ian R.
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supporting information
p. 1907 - 1912
(2020/10/06)
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- Triphosgene and DMAP as Mild Reagents for Chemoselective Dehydration of Tertiary Alcohols
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The utility of triphosgene and DMAP as mild reagents for chemoselective dehydration of tertiary alcohols is reported. Performed in dichloromethane at room temperature, this reaction is readily tolerated by a broad scope of substrates, yielding alkenes preferentially with the (E)-geometry. While formation of the Hofmann products is generally favored, a dramatic change in alkene selectivity toward the Zaitzev products is observed when the reaction is carried out in dichloroethane at reflux.
- Ganiu, Moshood O.,Cleveland, Alexander H.,Paul, Jarrod L.,Kartika, Rendy
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supporting information
p. 5611 - 5615
(2019/08/01)
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- Direct Oxidation of Csp3?H bonds using in Situ Generated Trifluoromethylated Dioxirane in Flow
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A fast, scalable, and safer Csp3?H oxidation of activated and un-activated aliphatic chains can be enabled by methyl(trifluoromethyl)dioxirane (TFDO). The continuous flow platform allows the in situ generation of TFDO gas and its rapid reactivity toward tertiary and benzylic Csp3?H bonds. The process exhibits a broad scope and good functional group compatibility (28 examples, 8–99 %). The scalability of this methodology is demonstrated on 2.5 g scale oxidation of adamantane.
- Lesieur, Mathieu,Battilocchio, Claudio,Labes, Ricardo,Jacq, Jér?me,Genicot, Christophe,Ley, Steven V.,Pasau, Patrick
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supporting information
p. 1203 - 1207
(2019/01/04)
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- Controllable Intramolecular Unactivated C(sp3)-H Amination and Oxygenation of Carbamates
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Dual catalyst-controlled intramolecular unactivated C(sp3)-H amination and oxygenation of carbamates merging visible-light photocatalysis and earth-abundant transition metal catalysis have been reported. Useful amino alcohol and diol derivatives could be selectively obtained from readily available tertiary alcohol derivatives. The possible mechanisms have been proposed via a 1,5-HAT process followed by Lewis acid-controlled cyclization. The nickel and zinc catalysts inhibit the formation of oxygenation and amination products, respectively. An interesting phenomenon of chirality transfer is also observed.
- Guo, Qihang,Ren, Xiang,Lu, Zhan
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supporting information
p. 880 - 884
(2019/05/16)
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- 7-azaspiro[5.6]dodecane-10-ketone compound as well as preparation method and application thereof
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The invention belongs to the field of medicine, and specifically relates to 7-azaspiro[5.6]dodecane-10-ketone compound as well as a preparation method and application thereof. According to the invention, a seven-membered ring structure is synthesized for the first time to obtain a novel compound with a better anti-tumor effect; reports of related structures have not been found; pharmacological studies show that the compound provided by the invention has certain inhibitory activity for human lung cancer A549 cells and human ovarian cancer OVCAR-3 cells, and provides a basis for subsequent preparation of anti-tumor drugs.
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Paragraph 0057-0060
(2019/09/05)
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- Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres
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3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C?OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.
- Croft, Rosemary A.,Mousseau, James J.,Choi, Chulho,Bull, James A.
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supporting information
p. 818 - 821
(2017/12/26)
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- Exploration of the diastereoselectivity in an unusual Grignard reaction and its application towards the synthesis of styryl lactones 7-: Epi -(+)-goniodiol and 8- epi -(-)-goniodiol
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An unusual diastereoselective Grignard reaction is explored, where the Grignard reagents are derived from 1,n-dihaloalkanes. A steric bias due to the presence of a quaternary centre adjacent to the acetonide ester at the benzylic position is responsible for the formation of an intramolecularly reduced product in almost quantitative yield. This steric hindrance is responsible for the diastereoselectivity observed with a variety of aromatic as well as aliphatic esters. The unusual Grignard reaction furnishes long chain secondary alcohols possessing a terminal olefin, which are synthetically important intermediates. As an application of this method, the diastereoselective synthesis of styryl lactones viz. 7-epi-(+)-goniodiol (29) and 8-epi-(-)-goniodiol (30) has been achieved.
- Chavan, Subhash P.,Khatod, Harshali S.,Das, Tamal,Vanka, Kumar
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p. 50721 - 50725
(2016/06/09)
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- The Barbier-Grignard-Type Arylation of Ketones and Unexpected Cross-Coupling of Phenolic Ketones using Unactivated Aryl Bromides
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A novel, highly versatile and efficient method has been developed for the Barbier-Grignard-type arylation of ketones and an unexpected cross-coupling of phenolic ketones was observed using unactivated bromides and magnesium in tetrahydrofuran/toluene at 96°C promoted by multicatalysts of cupric bromide (15 mol%), bismuth chloride (5 mol%) and silver bromide (10 mol%). The substituent and electronic effects on the reaction have been discussed. High yields of arylation and cross-coupling have been attained under mild conditions. A novel reasonable mechanism involving a quinone intermediate is proposed. The high chemical selectivity in the cross-coupling to the hydroxy group of phenolic ketones should help ketones find new applications.
- Wen, Yunming,Chen, Guifang,Huang, Shiqiang,Tang, Yu,Yang, Jun,Zhang, Yuanming
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p. 947 - 957
(2016/04/05)
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- Electron-deficient olefin ligands enable generation of quaternary carbons by Ni-catalyzed cross-coupling
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A Ni-catalyzed Negishi cross-coupling with 1,1-disubstituted styrenyl aziridines has been developed. This method delivers valuable β-substituted phenethylamines via a challenging reductive elimination that affords a quaternary carbon. A novel electron-deficient olefin ligand, Fro-DO, proved crucial for achieving high rates and chemoselectivity for C-C bond formation over β-H elimination. This ligand is easy to access, is stable, and presents a modular framework for reaction discovery and optimization. We expect that these attributes, combined with the fact that the ligands impart distinct electronic properties to a metal, will support the invention of new transformations not previously possible using established ligands.
- Huang, Chung-Yang,Doyle, Abigail G.
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supporting information
p. 5638 - 5641
(2015/05/20)
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- Iodine-Promoted Metal-Free Aromatization: Synthesis of Biaryls, Oligo p-Phenylenes and A-Ring Modified Steroids
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We describe efficient procedures based on the use of iodine for the synthesis of biaryls from arylcyclohexenols or arylcyclohexanols using sub-stoichiometric/catalytic iodine and dimethyl sulfoxide (DMSO) as oxidant. Heteroarylcyclohexanols also produced the corresponding biaryl products. It was proven that biphenyl can also be efficiently obtained when the quantity of iodine was reduced to 0.05 equiv. The method is compatible with different functional groups in the aromatic ring (either electron-donating or electron-withdrawing groups). For substrate scope, apart from cyclohexanone and cyclohexenone, some substituted cyclohexanones were also used to synthesize the starting arylcyclohexanols. The process was applied to the synthesis of oligo p-phenylenes and A-ring aromatized steroids, where the combined use of I2/DMSO not only provoked the necessary migration of the methyl group at C-10, but also further extended the conjugation.
- Domingo, Victoriano,Prieto, Consuelo,Castillo, Alexis,Silva, Lucia,Quílez Del Moral, José F.,Barrero, Alejandro F.
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supporting information
p. 3359 - 3364
(2015/11/03)
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- Copper-catalyzed allylation of a,a-difluoro-substituted organozinc reagents
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A method for the coupling of organozinc reagents, difluorocarbene, and allylic electrophiles is described. The reaction involves insertion of difluorocarbene into the carbon-zinc bond followed by copper-catalyzed allylic substitution.
- Zemtsov, Artem A.,Kondratyev, Nikolay S.,Levin, Vitalij V.,Struchkova, Marina I.,Dilman, Alexander D.
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p. 818 - 822
(2014/04/03)
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- A simple and efficient copper oxide-catalyzed Barbier-Grignard reaction of unactivated aryl or alkyl bromides with ester
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An efficient one-pot route to synthesize tertiary alcohol compounds using Barbier-Grignard reaction of unactivated alkyl or aryl bromides with ester in THF at 65 C catalyzed by CuO has been developed and systematically investigated. A wide range of substituted tertiary alcohol compounds were obtained in good to high yields. The reaction is highly chemoselective. The mechanism involving the leaving group of R2O-group is discussed.
- Gao, Fei,Deng, Xiang-Jun,Tang, Yu,Tang, Jin-Peng,Yang, Jun,Zhang, Yuan-Ming
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supporting information
p. 880 - 883
(2014/02/14)
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- Sequential one-pot addition of excess aryl-grignard reagents and electrophiles to O-alkyl thioformates
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The sequential addition of aromatic Grignard reagents to O-alkyl thioformates proceeded to completion within 30s to give aryl benzylic sulfanes in good yields. This reaction may begin with the nucleophilic attack of the Grignard reagent onto the carbon atom of the O-alkyl thioformates, followed by the elimination of ROMgBr to generate aromatic thioaldehydes, which then react with a second molecule of the Grignard reagent at the sulfur atom to form arylsulfanyl benzylic Grignard reagents. To confirm the generation of aromatic thioaldehydes, the reaction between O-alkyl thioformates and phenyl Grignard reagent was carried out in the presence of cyclopentadiene. As a result, hetero-Diels-Alder adducts of the thioaldehyde and the diene were formed. The treatment of a mixture of the thioformate and phenyl Grignard reagent with iodine gave 1,2-bis(phenylsulfanyl)-1,2-diphenyl ethane as a product, which indicated the formation of arylsulfanyl benzylic Grignard reagents in the reaction mixture. When electrophiles were added to the Grignard reagents that were generated insitu, four-component coupling products, that is, O-alkyl thioformates, two molecules of Grignard reagents, and electrophiles, were obtained in moderate-to-good yields. The use of silyl chloride or allylic bromides gave the adducts within 5min, whereas the reaction with benzylic halides required more than 30min. The addition to carbonyl compounds was complete within 1min and the use of lithium bromide as an additive enhanced the yields of the four-component coupling products. Finally, oxiranes and imines also participated in the coupling reaction. Into the melting pot: The addition of excess aryl Grignard reagents and electrophiles to O-alkyl thioformates gives aryl sulfanes through four-component coupling reactions (see scheme). These reactions may involve the formation of aromatic thioaldehydes and aryl-benzylic Grignard reagents as intermediates. For addition to carbonyl compounds, the use of lithium halides as an additive enhanced the efficiency of the reaction. Copyright
- Murai, Toshiaki,Morikawa, Kenta,Maruyama, Toshifumi
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p. 13112 - 13119
(2013/10/01)
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- Synthesis and antinociceptive behaviors of new methyl and hydroxyl derivatives of phencyclidine
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Phencyclidine (I) and its derivatives show such pharmacological behaviors as analgesic, anticonsulvant, anti-anxiety and antidepressant, while interacting with central nervous system. In this study, new methyl and hydroxyl derivatives of PCP were synthesized and their antinociceptive behaviors in animals were examined by measuring the number of writhing in a writhing test of visceral pain and the pain scores in Formalin test. Compared to control and PCP groups, findings in experimental groups indicated the new synthesized analogues (compounds II, III and V, 10 mg/kg) of PCP were able to produce more analgesic effects in formalin and writhing tests, especially for compound V. It was concluded that the new synthesized derivatives of PCP could substantially and respectively diminish acute and chronic pains.
- Ahmadi,Kermani,Naderi,Hajikhani,Rezaee,Javadi,Niknafs
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scheme or table
p. 763 - 769
(2012/06/30)
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- Rhodium(I)/diene-catalyzed addition reactions of arylborons with ketones
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Rh(I)/diene-catalyzed addition reactions of arylboroxines/arylboronic acids with unactivated ketones to form tertiary alcohols in good to excellent yields are described. By using C2-symmetric (3aR,6aR)-3,6-diaryl-1,3a,4,6a- tetrahydropentalenes as ligands, the asymmetric version of such an addition reaction, with up to 68% ee, was also realized.
- Liao, Yuan-Xi,Xing, Chun-Hui,Hu, Qiao-Sheng
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supporting information; experimental part
p. 1544 - 1547
(2012/06/05)
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- Ni-catalysed, domino synthesis of tertiary alcohols from secondary alcohols
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The use of in situ generated (NHC)-Ni catalytic species (NHC = N-heterocyclic carbene) allows for the synthesis, in short reaction times, of a variety of tertiary alcohols from secondary alcohols through a domino oxidation-addition protocol.
- Berini, Christophe,Navarro, Oscar
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p. 1538 - 1540
(2012/02/16)
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- Synthesis and application of 2,6-bis(trifluoromethyl)-4-pyridyl phosphanes: The most electron-poor aryl phosphanes with moderate bulkiness
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The poor will be rich: BFPy phosphanes (see scheme) mimic the electronic and steric characters of P(C6F5)3 and PPh 3, respectively. These novel ligands showed a large ligand acceleration effect on Stille coupling, the Rh-catalyzed 1,2-addition of aryl boronic acid to unactivated ketones and the asymmetric arylation of N-tosylimine using phenylboronic acid. Copyright
- Korenaga, Toshinobu,Ko, Aram,Uotani, Kotaro,Tanaka, Yuki,Sakai, Takashi
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supporting information; experimental part
p. 10703 - 10707
(2012/01/04)
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- Controlled alcohol-carbonyl interconversion by nickel catalysis
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All in one pot: A general synthetic platform allows the interconversion of alcohols and carbonyl compounds in a predictable and controlled fashion in one pot. Under the action of a Ni catalyst, PhCl, CsF, and arylboronates, several multistep alcohol-carbonyl interconversions have been achieved with good overall efficiency (see scheme). A one-pot nickel-catalyzed synthesis of flumecinol (a hepatic microsomal enzyme inducer) has also been demonstrated. Copyright
- Maekawa, Takehisa,Sekizawa, Hiromi,Itami, Kenichiro
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p. 7022 - 7026
(2011/09/30)
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- Structure-guided design and synthesis of P1′ position 1-phenylcycloalkylamine-derived pentapeptidic BACE1 inhibitors
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Previously, we reported potent pentapeptidic BACE1 inhibitors with the hydroxymethylcarbonyl isostere as a substrate transition-state mimic. To improve the in vitro potency, we further reported pentapeptidic inhibitors with carboxylic acid bioisosteres at the P4 and P1′ positions. In the current study, we screened new P1′ position 1-phenylcycloalkylamine analogs to find non-acidic inhibitors that possess double-digit nanomolar range IC50 values. An extensive structure-activity relationship study was performed with various amine derivatives at the P1′ position. The most potent inhibitor of this pentapeptide series, KMI-1830, possessing 1-phenylcyclopentylamine at the P 1′ position had an IC50 value of 11.6 nM against BACE1 in vitro enzymatic assay.
- Tagad, Harichandra D.,Hamada, Yoshio,Nguyen, Jeffrey-Tri,Hidaka, Koushi,Hamada, Takashi,Sohma, Youhei,Kimura, Tooru,Kiso, Yoshiaki
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experimental part
p. 5238 - 5246
(2011/10/08)
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- Enantioselective nitroaldol reaction catalyzed by sterically modified salen-chromium complexes
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A group of modified (salen)Cr(III)Cl complexes with bulky benzylic substituents in the 3,3'-position of the salicylidene moiety have been successfully applied for the asymmetric nitroaldol reaction. The readily accessible complex bearing 3-phenylpent-3-yl groups (2 mol %) leads to β-nitro alcohols in up to 92% yield and 94% ee.
- Kowalczyk, Rafal,Kwiatkowski, Piotr,Skarzewski, Jacek,Jurczak, Janusz
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supporting information; experimental part
p. 753 - 756
(2009/06/28)
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- Cobalt-Catalyzed Oxidations in Volumetrically Expanded Liquids by Compressed Gases
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Oxidations of hydrocarbons, cycloalkanes and alkenes, arylalkanes, and a variety of other organic substrates are accomplished by cobalt-N-hydroxysuccinimide co-catalyzed reactions with dioxygen under unusually mild, near ambient conditions of temperature and pressure. The improved safety of the oxidation method and the high yields of product obtained make use of a unique combination of cobalt (II) complexes with N-hydroxysuccinimide. These autoxidation reactions do not have prolonged initiation times. Many of these reactions can be safely performed under normal chemical laboratory conditions and do not require specialized equipment or reagents.
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Page/Page column 7
(2008/12/06)
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- Synthesis of hexahydrocyclopenta[c]furans by an intramolecular iron-catalyzed ring expansion reaction
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The intramolecular iron-catalyzed ring expansion reaction of epoxyalkenes was investigated with a preformed iron(salen) [Fe(Salen)] complex. The formal insertion of the alkene into the epoxide generated hexahydrocyclopenta[c]furan derivatives in moderate to good yields and diastereoselectivities depending on other functional groups present in the starting materials. In addition, oxygen-tethered epoxyalkenes were used for the synthesis of lignan isomers. The scope and limitations of the Fe (Salen)-catalyzed process of the reaction are discussed.
- Hilt, Gerhard,Bolze, Patrick,Heitbaum, Maja,Hasse, Katrin,Harms, Klaus,Massa, Werner
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p. 2018 - 2026
(2008/09/17)
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- Rhodium-catalyzed addition of arylboron compounds to nitriles, ketones, and imines
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The rhodium-catalyzed addition reactions of sodium tetraphenylborate and arylboronic acids to nitriles, ketones, and imines were examined. The reaction of nitriles could be carried out efficiently in the presence of a catalyst system of [RhCl(cod)]2-dppp and H2O to give the corresponding monoarylated products selectively. Although unactivated ketones and imines are known to be poor electrophiles for rhodium-catalyzed arylation, the phenylation of them with use of sodium tetraphenylborate proceeded smoothly in the presence of [RhCl(cod)]2 and Rh(acac)(cod) as catalysts, respectively. The addition of NH4Cl was found to be crucial to effectively conduct the reaction of ketones and imines.
- Ueura, Kenji,Miyamura, Sawako,Satoh, Tetsuya,Miura, Masahiro
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p. 2821 - 2826
(2007/10/03)
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- Modern Friedel-Crafts chemistry. Part-271. Alkylation of benzene with 1-benzyl- and 1-phenylcyclohexanols in the presence of H 2SO4 and AlCl3/CH3NO2 catalysts
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The alkylation of benzyene with 1-benzylcyclohexanol (3) gave a mixture of 2,3-benzobicyclo[3.3.1]nona-2-ene (8, 79%) and cyclohexyldiphenylmethane (10, 21%) with AlCl3/CH3NO2 catalyst and a mixture of 1-benzylcyclohexene 5 (47.5%), 8 (8%), 10 (21.5%), 1-cyclopentyl-1,2- diphenylethane (12, 18%) and 1-benzyl-1-phenylcyclohexene (13, 4%) with H 2SO4 catalyst. Treatment of 3 with AlCl 3/CH3NO2 in petroleum ether gave a mixture of 5 (26%) and 8 (62%). Attempted alkylation of benzene with 1-phenylcyclohexanol (4) in the presence of either AlCl3/CH3NO2 or H2SO4 catalyst gave 1-(1-phenylcyclohexyl)-2- phenylcyclohexene (17) as sole product. Mechanistic interpretation of the results in terms of carbocation behaviour is offered.
- Khalaf, Ali A.,Awad, Ibrahim M.,El-Emary, Talaat I.,Abd El-Aal, Hassan A. K.
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p. 1018 - 1022
(2007/10/03)
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- Synthesis with improved yield and study on the analgesic effect of 2-methoxyphencyclidine
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Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of Its derivatives have been synthesized and their biological properties were studied. Since a methoxy group has been added to the position 2 of the cyclohexane ring of PCP, the resulting compound is more polar than PCP. This compound was synthesized using an improved method with a higher yield. Its analgesic effect was studied using the tail-flick test on rats and was compared with that of ketamine (CAS 1867-66-9). The results showed that 2-methoxyphencyclidine increased tail-flick latencies as compared to the control group. The maximum analgesic effect of the compound occurred 5-10 min after its injection, while the effect of ketamine was observed 10-25 min after injection. ECV · Editio Cantor Verlag.
- Ahmadi, Abbas,Mahmoudi, Ali
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p. 346 - 350
(2007/10/03)
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- Cyclopentyl sulfonamide derivatives
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The present invention provides compounds of formula (I): useful for potentiating glutamate receptor function in a mammal and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.
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- Photolysis of 1-alkylcycloalkanols in the presence of (diacetoxyiodo) benzene and I2. Intramolecular selectivity in the β-scission reactions of the intermediate 1-alkylcycloalkoxyl radicals
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The C-C β-scission reactions of 1-alkylcycloalkoxyl radicals, generated photochemically by visible light irradiation of CH2Cl 2 solutions containing the parent 1-alkylcycloalkanols, (diacetoxy)-iodobenzene (DIB), and I2, have been investigated through the analysis of the reaction products. The 1-alkylcycloalkoxyl radicals undergo competition between ring opening and C-alkyl bond cleavage as a function of ring size and of the nature of the alkyl substituent. With the 1-propylcycloheptoxyl, 1-propylcyclooctoxyl, and 1-phenylcyclooctoxyl radicals, formation of products deriving from an intramolecular 1,5-hydrogen atom abstraction reaction from the cycloalkane ring has also been observed. The results are discussed in terms of release of ring strain associated to ring opening, stability of the alkyl radical formed by C-alkyl cleavage, and with cycloheptoxyl and cyclooctoxyl radicals, also in terms of the possibility of achieving a favorable geometry for intramolecular hydrogen atom abstraction.
- Antunes, Carla S. Aureliano,Bietti, Massimo,Lanzalunga, Osvaldo,Salamone, Michela
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p. 5281 - 5289
(2007/10/03)
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- Rhodium-catalyzed addition of arylstannanes to carbon-heteroatom double bond
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The addition of arylstannanes to the carbon-heteroatom double bond in the presence of a catalytic amount of a cationic rhodium complex ([Rh(cod)(MeCN)2]BF4) was examined. The reactions of aldehydes, α-dicarbonyl compounds, and N-substituted aldimines with the arylstannanes gave corresponding alcohols, α-hydroxy carbonyl compounds, and amines, respectively. An arylrhodium complex generated by the transmetalation with the arylstannane was probably the active catalytic species.
- Oi, Shuichi,Moro, Mitsutoshi,Fukuhara, Hiroe,Kawanishi, Takanori,Inoue, Yoshio
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p. 4351 - 4361
(2007/10/03)
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- Reductive defluorination of fluoroalkanes
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The reaction of an excess of lithium powder and a catalytic amount of DTBB with primary, secondary and tertiary fluoroalkanes in the presence of a substoichiometric amount of 1,2-bis(trimethylsilyl)benzene 1 afforded the corresponding alkanes resulting from a fluorine-hydrogen exchange. The method could be extended to non-geminal difluorides. The effect of the disilylated compound in the naphthalene-catalysed lithiation of fluorobenzene and benzyl fluoride was also studied.
- Guijarro, David,Martínez, Pedro,Yus, Miguel
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p. 1237 - 1244
(2007/10/03)
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- Oxidative fragmentation of 1-aryl-1-cycloalkenes using cerium(IV) ammonium nitrate (CAN): Some novel observations
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1-Phenyl-1-cycloalkenes undergo oxidative fragmentation in presence of CAN in methanol, affording 1,n-dicarbonyl compounds as the major products along with 1,2-dimethoxycycloalkanes. The reaction under deoxygenated conditions afforded the latter in good yields. In the presence of azide ion, fragmentation leading to the corresponding cyanoketones was observed whereas with sulfinate only the 1-methoxy-2-sulfonyl cycloalkanes were formed.
- Nair, Vijay,Panicker, Sreeletha B,Thomas, Siji,Santhi,Mathai, Sindhu
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p. 3229 - 3234
(2007/10/03)
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- Acetonyltriphenylphosphonium bromide and its polymer-supported analogues as catalysts in protection and deprotection of alcohols as alkyl vinyl ethers
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Both acetonyltriphenylphosphonium bromide (ATPB, 1) and poly-p-styryldiphenylacetonylphosphonium bromide (A) were effective catalysts in the protection of alcohols as THP, THF, and EE ethers as well as the cleavage of THP, THF, and EE ethers to the corresponding alcohols. They could be applied to 1°, 2° and 3° alcohols, phenol and acid-labile alcohols. Both ATPB and catalyst A are excellent catalysts in the present study. It needed only 1×10-2-1.25×10-2 mol equiv. of the polymer-supported catalyst A in the reactions.
- Hon, Yung-Son,Lee, Chia-Fu,Chen, Rong-Jiunn,Szu, Ping-Hui
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p. 5991 - 6001
(2007/10/03)
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- Arene-catalysed lithiation of fluoroarenes
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The reaction of different fluoroarenes 1 with lithium and a catalytic amount (7%) of naphthalene in THF at -30°C affords the corresponding aryllithium intermediates which, by reaction with several electrophiles at temperatures ranging between -30 and 0°C, lead to the expected products 2, after hydrolysis. (C) 2000 Elsevier Science Ltd.
- Guijarro, David,Yus, Miguel
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p. 1135 - 1138
(2007/10/03)
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- NiCl2/CrCl2-mediated coupling reaction of ketones with alkenyl(or alkynyl, aryl) halides accomplished in the presence of a bipyridyl-type ligand
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In this work, alkenyl halides (or triflates) and alkynyl (or aryl) halides are readily coupled with ketones in tetrahydrofuran in the presence of ligand 1, NiCl2 and CrCl2 at room temperature subsequently yielding the corresponding allylic alcohols, propargylic alcohols and benzylic alcohols.
- Chen, Chinpiao
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p. 1311 - 1312
(2007/10/03)
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- Rhodium-catalysed arylation of aldehydes with arylstannanes
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Aryltrimethylstannanes react with aldehydes in the presence of a catalytic amount of a cationic rhodium complex, [Rh(cod)(MeCN)2]BF4, affording the corresponding arylated secondary alcohols in good yields.
- Oi, Shuichi,Moro, Mitsutoshi,Inoue, Yoshio
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p. 1621 - 1622
(2007/10/03)
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