- Iron-Catalyzed Vinylzincation of Terminal Alkynes
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Organozinc reagents are among the most commonly used organometallic reagents in modern synthetic chemistry, and multifunctionalized organozinc reagents can be synthesized from structurally simple, readily available ones by means of alkyne carbozincation. However, this method suffers from poor tolerance for terminal alkynes, and transformation of the newly introduced organic groups is difficult, which limits its applications. Herein, we report a method for vinylzincation of terminal alkynes catalyzed by newly developed iron catalysts bearing 1,10-phenanthroline-imine ligands. This method provides efficient access to novel organozinc reagents with a diverse array of structures and functional groups from readily available vinylzinc reagents and terminal alkynes. The method features excellent functional group tolerance (tolerated functional groups include amino, amide, cyano, ester, hydroxyl, sulfonyl, acetal, phosphono, pyridyl), a good substrate scope (suitable terminal alkynes include aryl, alkenyl, and alkyl acetylenes bearing various functional groups), and high chemoselectivity, regioselectivity, and stereoselectivity. The method could significantly improve the synthetic efficiency of various important bioactive molecules, including vitamin A. Mechanistic studies indicate that the new iron-1,10-phenanthroline-imine catalysts developed in this study have an extremely crowded reaction pocket, which promotes efficient transfer of the vinyl group to the alkynes, disfavors substitution reactions between the zinc reagent and the terminal C–H bond of the alkynes, and prevents the further reactions of the products. Our findings show that iron catalysts can be superior to other metal catalysts in terms of activity, chemoselectivity, regioselectivity, and stereoselectivity when suitable ligands are used.
- Huang, Qiang,Su, Yu-Xuan,Sun, Wei,Hu, Meng-Yang,Wang, Wei-Na,Zhu, Shou-Fei
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p. 515 - 526
(2022/01/08)
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- Compound of dipyrrolopyridine structure Preparation method and medical application
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The invention discloses a compound with a dipyrrolo-pyridine structure as well as a preparation method and medical application thereof. The compound provided by the invention has obvious inhibitory activity on JAK family proteins, is an effective JAK inhibitor, and has the prospect of being developed into drugs for inhibiting JAK and further treating diseases.
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Paragraph 0147; 0151-0153
(2021/08/25)
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- Ruthenium-Catalyzed Propargylic Reduction of Propargylic Alcohols with Hantzsch Ester
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Ruthenium-catalyzed propargylic reduction of propargylic alcohols bearing a terminal alkyne moiety is accomplished by using Hantzsch ester as a nucleophilic hydride source. A variety of secondary and tertiary propargylic alcohols are reduced to the corresponding propargylic reduced products such as 1-alkynes in excellent yields. Some mechanistic studies indicate that ruthenium-allenylidene complexes may work as key reactive intermediates.
- Ding, Haowei,Sakata, Ken,Kuriyama, Shogo,Nishibayashi, Yoshiaki
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supporting information
p. 2130 - 2134
(2020/06/08)
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- Novel multitarget inhibitors with antiangiogenic and immunomodulator properties
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By means of docking studies, seventeen compounds T.1-T17 have been designed and evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins in order to overcome resistance phenomena offered by cancer. All these designed molecules display a urea moie
- Conesa-Milián, Laura,Falomir, Eva,Murga, Juan,Carda, Miguel,Marco, J. Alberto
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- HISTONE DEMENTHYLASE INHIBITORS
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The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrrolopyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject com
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Paragraph 00175
(2014/10/18)
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- Highly regioselective nickel-catalyzed cross-coupling of N -tosylaziridines and alkylzinc reagents
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Herein, we report the first ligand-controlled, nickel-catalyzed cross-coupling of aliphatic N-tosylaziridines with aliphatic organozinc reagents. The reaction protocol displays complete regioselectivity for reaction at the less hindered C-N bond, and the products are furnished in good to excellent yield for a broad selection of substrates. Moreover, we have developed an air-stable nickel(II) chloride/ligand precatalyst that can be handled and stored outside a glovebox. In addition to increasing the activity of this catalyst system, this also greatly improves the practicality of this reaction, as the use of the very air-sensitive Ni(cod)2 is avoided. Finally, mechanistic investigations, including deuterium-labeling studies, show that the reaction proceeds with overall inversion of configuration at the terminal position of the aziridine by way of aziridine ring opening by Ni (inversion), transmetalation (retention), and reductive elimination (retention).
- Jensen, Kim L.,Standley, Eric A.,Jamison, Timothy F.
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supporting information
p. 11145 - 11152
(2014/08/18)
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- Enantioselective Synthesis of the Tricyclic Core of FR901483 Featuring a Rhodium-Catalyzed [2+2+2] Cycloaddition
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An efficient approach to the tricyclic framework of FR901483 is described. The sequence features a [3,3]-sigmatropic rearrangement of a cyanate to an isocyanate, followed by its subsequent asymmetric rhodium-catalyzed [2+2+2] cycloaddition with a terminal
- Perreault, Stéphane,Rovis, Tomislav
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p. 719 - 728
(2013/04/23)
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- Polycyanurate networks from dehydroanethole cyclotrimers: Synthesis and characterization
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Novel biobased trisphenols were obtained by palladium- and cobalt-catalyzed [2 + 2 + 2] cycloaddition of dehydroanethole isomers which were readily prepared from the natural product trans-anethole. The trisphenols were transformed into their corresponding
- Davis, Matthew C.,Guenthner, Andrew J.,Sahagun, Christopher M.,Lamison, Kevin R.,Reams, Josiah T.,Mabry, Joseph M.
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p. 6902 - 6909
(2014/01/06)
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- Biarylphosphonite gold(I) complexes as superior catalysts for oxidative cyclization of propynyl arenes into indan-2-ones
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Striking gold: A series of variously functionalized propynyl arenes was smoothly converted into indan-2-ones by a new gold(I)-catalyzed oxidative cyclization process. [LAu]NTf2 (Tf=trifluoromethanesulfonyl) is a superior catalyst both in terms of yield and kinetics for the present transformation. Copyright
- Henrion, Guilhem,Chavas, Thomas E. J.,Le Goff, Xavier,Gagosz, Fabien
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supporting information
p. 6277 - 6282
(2013/07/11)
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- Synthesis of allenes via Nickel-catalyzed cross-coupling reaction of propargylic bromides with grignard reagents
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We describe a convenient method for the synthesis of terminal allenes from cross-coupling of propargylic bromide with Grignard reagent. The reaction of propargylic bromide with 1.2 equivalents of Grignard reagent mediated by Ni(acac)2 (2 mol%) and Ph3P (4 mol%) in THF may produce terminal allenes in good yields and high regioselectivities at room temperature. Georg Thieme Verlag Stuttgart · New York.
- Li, Qinghan,Gau, Hanmou
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experimental part
p. 747 - 750
(2012/06/29)
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- Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis
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Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, w
- Jie, Jack Li,Nahra, Joe,Johnson, Adam R.,Bunker, Amy,O'Brien, Patrick,Yue, Wen-Song,Ortwine, Daniel F.,Man, Chiu-Fai,Baragi, Vijay,Kilgore, Kenneth,Dyer, Richard D.,Han, Hyo-Kyung
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p. 835 - 841
(2008/09/20)
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- Matrix metalloproteinase inhibitors
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Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1' channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.
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- 3-[5-substituted benzyl)amino]-2-phenylpiperidines as substance P antagonists
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This invention provides a compound of the formula: STR1 and its pharmaceutically acceptable salts, wherein R 1 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, halo C 1 -C 6 alkyl or terahydropyranyl, having one or more substituents selected from cyano, 1,3-thiazolanyl, COOR 2, COR 2, OCOR 2, CONR 3 R 4, NR 3 R 4, NR 5 COR 3 and C.ident.CR 6, wherein R 2 is hydrogen or C 1 -C 4 alkyl, R 3 and R 4 are independently hydrogen, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl, R 5 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl and R 6 is hydrogen, halo, cyano, C 1 -C 6 alkyl, COOH, COO(C 1 -C 4 alkyl) or phenyl; X is C 1 -C 6 alkoxy or halo C 1 -C 6 alkoxy; and Ar is phenyl optionally substituted with halo.These compounds are useful in the treatment of allergic disorders, angiogenesis, gastrointestinal disorders, central nervous system disorders, inflammatory diseases, emesis, urinary incontinence, pain, migraine, sunburn, and diseases, disorders and adverse conditions caused by Helicobacter pylori, in a mammalian subject.
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- Conversion of alkyl- and arylallenes into 1-alkynes through metallated intermediates
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A number of acetylenes RCH2C≡CH have been obtained by metallation of the allenes RCH=C=CH2 or mixtures of acetylenes and allenes with n-BuLi in THF-hexane and hydrolysis after allowing the metallated allenes to rearrange at roam temperature or by heating under reflux.
- Taherirastgar,Brandsma
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p. 4035 - 4040
(2007/10/03)
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- Ipso Selectivity in the Reductive Iodonio-Claisen Rearrangement of Allenyl(p-methoxyaryl)iodinanes
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Allenyl(aryl)iodinanes, generated from p-methoxy(diacetoxyiodo)arenes by the reaction with propyn-2-yl(trimethyl)silanes in the presence of BF3-Et2O in dichloromethane, undergo reductive ipso iodonio-Claisen rearrangement selectively at -20 deg C yielding
- Ochiai, Masahito,Ito, Takao,Masaki, Yukio
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- A NOVEL AND EFFICIENT METHOD TO PREPARE 3-(HETERO)ARYL-1-PROPYNES AND ITS APPLICATION TO THE STEREOSELECTIVE SYNTHESIS OF (2E,4E)-N-(2-METHYLPROPYL)-6-(2-METHYLPROPYL)-6-(2-THIENYL)-2,4-HEXADIENAMIDE, PIPEROVATINE AND (E)-N-(2-METHYLPROPYL)-6-(4-METHOXYPHENYL)-4-HEXYN-2-ENAMIDE
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Chemically pure 3-(hetero)aryl-1-propynes, 13, have been prepared in high overall yields by a novel method which involves: (a) a copper(I)-mediated cross-coupling between a halomethyl(hetero)arene, 16, and trimethylsilylethylmagnesium bromide, 17, to give a trimethylsilyl-3-(hetero)aryl-1-propyne, 18; (b) removal of the trimethylsilyl group from 18 by treatment with potassium fluoride dihydrate in DMF.One of these 1-alkynes, i.e. 3-(2-thienyl)-1-propyne, 13a, has been employed in the key step of a highly stereoselective synthesis of naturally-occurring (2E,4E)-N-(2-methylpropyl)-6-(2-thienyl)-2,4-hexadienamide, 6.On the other hand, 3-(4-methoxyphenyl)-1-propyne, 13b, has been used either in two stereoselective syntheses of another natural N-(2-methylpropyl) amide, i.e. piperovatine, 7, or in the preparation of a structural analogue of 7, i.e. (E)-N-(2-methylpropyl)-6-(4-methoxyphenyl)-4-hexyn-2-enamide, 15.
- Rossi, Renzo,Carpita, Adriano,Lippolis, Vito,Benetti, Massimo
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p. 783 - 791
(2007/10/02)
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- MEDICINAL PLANTS OF SOUTHERN AFRICA. PART 2. SYNTHESIS OF 1,3-BIS-(4-METHOXYPHENYL)PENTA-1,4-DIENE, A STEREOISOMER OF DIMETHYLHINOKIRESINOL, AND ITS 4-MONOMETHOXY ANALOGUE
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A six-step synthesis of the title compounds (6) and (7) from prop-2-yn-1-ol, and proceeding via 3-(4-methoxyphenyl)prop-1-yne, is described.Detailed 1H n.m.r. spectral analysis (500 MHz) suggests that the synthetic compounds have a 1,2-E stereochemistry in contrast to the Z-configuration present in the naturally occurring hinokiresinol (3).By utilizing a different, and much less efficient route, a small quantity of (Z)-3-(4-methoxyphenyl)-1-phenylpenta-1,4-diene (5) was obtained.
- Ameer, Farouk,Drewes, Siegfried E.,Drewes, Mark W.,Roos, Gregory H. P.,Watson, Martin C.
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p. 1425 - 1430
(2007/10/02)
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- SYNTHETIC APPROACHES TO ISOBUTYLAMIDES OF INSECTICIDAL INTEREST
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Syntheses of 10,11-dehydro- and 10,11-(Z)-pipercide, piperovatin, and an ene-yne, and a perfluoro-isobutylamide, illustrate the utility of hydrozirconation methodology in this area.
- Crombie, Leslie,Horsham, Mark A.,Blade, Robert J.
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p. 4879 - 4882
(2007/10/02)
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