- Iron-Catalyzed Borrowing Hydrogen C-Alkylation of Oxindoles with Alcohols
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A general and efficient iron-catalyzed C-alkylation of oxindoles has been developed. This borrowing hydrogen approach employing a (cyclopentadienone)iron carbonyl complex (2 mol %) exhibited a broad reaction scope, allowing benzylic and simple primary and secondary aliphatic alcohols to be employed as alkylating agents. A variety of oxindoles underwent selective mono-C3-alkylation in good-to-excellent isolated yields (28 examples, 50–92 % yield, 79 % average yield).
- Dambatta, Mubarak B.,Polidano, Kurt,Northey, Alexander D.,Williams, Jonathan M. J.,Morrill, Louis C.
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p. 2345 - 2349
(2019/05/16)
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- Enabling CO Insertion into o-Nitrostyrenes beyond Reduction for Selective Access to Indolin-2-one and Dihydroquinolin-2-one Derivatives
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The transition metal-catalyzed reductive cyclization of o-nitrostyrene in the presence of carbon monoxide (CO) has been developed to be a general synthetic route to an indole skeleton, wherein CO was used as a reductant to deoxidize nitroarene into nitrosoarene and/or nitrene with CO2 release, but the selective insertion of CO into the heterocyclic product with higher atom economy has not yet been realized. Herein, the Pd-catalyzed reduction of o-nitrostyrene by CO and its regioselective insertion were efficiently achieved to produce synthetically useful five- and six-membered benzo-fused lactams. Detailed investigations revealed that the chemoselectivity to indole or lactam was sensitive to the nature of the counteranions of Pd2+ precursors, whereas ligands significantly decided the carbonylative regioselectivity by different reaction pathways. Using PdCl2/PPh3/B(OH)3 (condition A), an olefin hydrocarboxylation was primarily initiated followed by partial reduction of the NO2 moiety and cyclization reaction to give N-hydroxyl indolin-2-one, which was further catalytically reduced by CO to afford the indolin-2-one as the final product with up to 95% yield. When the reaction was conducted under the Pd(TFA)2/BINAP/TsOH·H2O system (condition B), complete deoxygenation and carbonylation of the NO2 group occurred initially to yield the corresponding isocyanate followed by internal hydrocyclization to generate 3,4-dihydroquinolin-2-one with up to 98% yield. Importantly, the methodology could be efficiently applied in the synthesis of marketed drug Aripiprazole.
- Yang, Li,Shi, Lijun,Xing, Qi,Huang, Kuo-Wei,Xia, Chungu,Li, Fuwei
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p. 10340 - 10348
(2018/10/20)
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- Biocatalysed olefin reduction of 3-alkylidene oxindoles by baker's yeast
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3-Substituted oxindoles are very interesting molecules both for their potential biological activity and for their role as starting materials toward more complex oxindole-based structures. These molecules can be prepared by the reduction of a 3-ylidene oxi
- Rossetti, Arianna,Sacchetti, Alessandro,Bonfanti, Marta,Roda, Gabriella,Rainoldi, Giulia,Silvani, Alessandra
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p. 4584 - 4590
(2017/07/11)
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- Magnesium-Catalyzed Electrophilic Trifluoromethylation: Facile Access to All-Carbon Quaternary Centers in Oxindoles
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The first example of a magnesium-catalyzed direct trifluoromethylation of 3-substituted oxindoles using an electrophilic hypervalent iodine reagent is reported. The reaction proceeds under unprecedented mild conditions leading to the formation of an all-carbon quaternary center in oxindoles in high chemical yield and demonstrates excellent functional group tolerance. In addition to trifluoromethyl, other perfluoroalkyl groups can be introduced with similar level of efficacy. Mechanistic investigations are consistent with the involvement of a radical pathway. The chemical versatility of the obtained products is further illustrated through their conversion in situ into valuable organofluorine building blocks, making the protocol more widely applicable.
- Katayev, Dmitry,Kajita, Harutake,Togni, Antonio
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supporting information
p. 8353 - 8357
(2017/06/28)
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- Evaluation of 3-ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET ligands for the serotonin 5-HT7 receptor: Synthesis, pharmacology, radiolabeling, and in vivo brain imaging in pigs
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We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are de
- Herth, Matthias M.,Andersen, Valdemar L.,Hansen, Hanne D.,Stroth, Nikolas,Volk, Balázs,Lehel, Szabolcs,Dyssegaard, Agnete,Ettrup, Anders,Svenningsson, Per,Knudsen, Gitte M.,Kristensen, Jesper L.
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supporting information
p. 3631 - 3636
(2015/05/05)
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- Regiodivergent access to five- and six-membered benzo-fused lactams: Ru-catalyzed olefin hydrocarbamoylation
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We report herein a new strategy of the Ru-catalyzed intramolecular olefin hydrocarbamoylation for the regiodivergent synthesis of five- and six-membered benzo-fused lactams starting from N-(2-alkenylphenyl)formamides. Using a combined catalyst of Ru3
- Li, Bin,Park, Yoonsu,Chang, Sukbok
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p. 1125 - 1131
(2014/02/14)
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- Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT7 receptor antagonist activity
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A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT 7 receptor antagonists has been studied for their selectivity toward the 5-HT1A receptor and α1-adrenoceptor. Several derivatives exhibited high 5-HT7
- Volk, Balázs,Gacsályi, István,Pallagi, Katalin,Poszávácz, László,Gy?n?s, Ildikó,Szabó, éva,Bakó, Tibor,Spedding, Michael,Simig, Gyula,Szénási, Gábor
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scheme or table
p. 6657 - 6669
(2011/12/02)
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- C-3 alkylation of oxindole with alcohols catalyzed by an indene-functionalized mesoporous iridium catalyst
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A heterogeneous indene-based iridium catalyst with a highly ordered dimensional-hexagonal mesostructure was prepared through complexation of IrCl3 with the indene-functionalized SBA-15 silica materials. During C-3 alkylation of oxindole with va
- Liu, Guohua,Huang, Tianzeng,Zhang, Yuli,Liang, Xiaohui,Li, Yunsheng,Li, Hexing
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experimental part
p. 655 - 659
(2012/01/12)
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- Direct N-carbamoylation of 3-monosubstituted oxindoles with alkyl imidazole carboxylates
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(Chemical Equation Presented) Regioselective N-carbamoylation of oxindoles was achieved through the use of imidazole carboxylate reagents. This reaction provides ready access to N-carbamoyl-3-monosubstituted oxindoles.
- Trost, Barry M.,Zhang, Yong,Zhang, Ting
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supporting information; experimental part
p. 5115 - 5117
(2009/10/24)
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- Iridium catalysed C-3 alkylation of oxindole with alcohols under solvent free thermal or microwave conditions
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Ir-catalysed alkylation of oxindole and N-methyl oxindole with a range of substituted benzyl and heteroaryl alcohols under solvent free thermal or microwave conditions afforded the corresponding C-3-monoalkylated products in high to excellent yield.
- Grigg, Ronald,Whitney, Simon,Sridharan, Visuvanathar,Keep, Ann,Derrick, Andrew
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experimental part
p. 4375 - 4383
(2009/10/17)
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- Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)- 1-methyl-1H-pyrrole-2-carbonitrile (WAY-255348)
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We have continued to explore the 3,3-dialkyl-5-aryloxindole series of progesterone receptor (PR) modulators looking for new agents to be used in female healthcare: contraception, fibroids, endometriosis, and certain breast cancers. Previously we reported
- Fensome, Andrew,Adams, William R.,Adams, Andrea L.,Berrodin, Tom J.,Cohen, Jeff,Huselton, Christine,Illenberger, Arthur,Kern, Jeffrey C.,Hudak, Valerie A.,Marella, Michael A.,Melenski, Edward G.,McComas, Casey C.,Mugford, Cheryl A.,Slayden, Ov D.,Yudt, Matthew,Zhang, Zhiming,Zhang, Puwen,Zhu, Yuan,Winneker, Richard C.,Wrobel, Jay E.
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p. 1861 - 1873
(2008/12/20)
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- (Phenylpiperazinyl-butyl)oxindoles as selective 5-HT7 receptor antagonists
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A series of potent 5-hydroxytryptamine7 (5-HT7) ligands has been synthesized that contain a 1,3-dihydro2H-indol-2-one (oxindole) skeleton. The binding of these compounds to the 5-HT7 and 5-HT 1A receptors was measured. Despite the structural similarity of these two serotonin receptor subtypes, several derivatives exhibited a high selectivity to the 5-HT7 receptor. According to the structure-activity relationship observations, compounds unsubstituted at the oxindole nitrogen atom and containing a tetramethylene spacer between the oxindole skeleton and the basic nitrogen atom are the most potent ligands. Concerning the basic group, besides the moieties of the 4-phenylpiperazine type, halophenyl-1,2,3,6-tetrahydropyridines also proved to be 5-HT7 receptor-ligands. Because of halogen substitution on the aromatic rings, good metabolic stability could be achieved. A representative of the family, 3-{4-[4-(4-chlorophenyl)-piperazin-1-yl]-butyl}-3-ethyl-6-fluoro-1, 3-dihydro-2H-indol-2-one (9e′) exhibited selective 5-HT7 antagonist activity (K: = 0.79 nM). The in vivo pharmacological potencies of these 5-HT7 receptor-ligands were estimated by the conflict drinking (Vogel) and the light-dark anxiolytic tests.
- Volk, Balázs,Barkóczy, József,Hegedus, Endre,Udvari, Szaboles,Gacsályi, István,Mezei, Tibor,Pallagi, Katalin,Kompagne, Hajnalka,Lévay, Gy?rgy,Egyed, András,Hársing Jr., Lásló G.,Spedding, Michael,Simig, Gyula
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p. 2522 - 2532
(2008/12/23)
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- Reduction of 3-acyl derivatives of oxindoles, benzo[b]furan-2-ones, and benzo[b]thiophen-2-ones to the corresponding alkyl derivatives by sodium borohydride-acetic acid
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It was found that 3-acyl derivatives of oxindoles, benzo[b]furan-2-ones, and benzo[b]thiophen-2-ones could be efficiently and conveniently reduced to the corresponding alkyl derivatives by pelletized sodium borohydride in acetic acid. A typical procedure
- Smith, Francis X.,Williams, Brian D.,Gelsleichter, Eric,Podcasy, Judy A.,Sisko, John T.,Hrubowchak, David M.
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p. 765 - 769
(2007/10/03)
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- Progesterone receptor modulators comprising pyrrole-oxindole derivatives and uses thereof
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Pyrrole-oxindole derivatives useful as progesterone receptor antagonists are provided. Pharmaceutical compositions containing these derivatives are described, as is the use thereof in contraception and hormone-related conditions.
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-
Page/Page column 8-9
(2010/02/15)
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- Recyclable selective palladium-catalyzed synthesis of five-, six- or seven-membered ring lactones and lactams by cyclocarbonylation in ionic liquids
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The ionic liquids, BMIM PF6 or BMIM NTf2, are used successfully for the palladium-catalyzed cyclocarbonylation of 2-allylphenols and anilines, 2-vinylphenols, and 2-aminostyrenes. The reaction proceeds cleanly and efficiently to afford high yields of lactones or lactams with good or excellent selectivity for one isomer. The ionic liquid containing the palladium catalyst, and ligand, is recyclable in all cases.
- Ye, Fangguo,Alper, Howard
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p. 1855 - 1861
(2007/10/03)
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- Horseradish peroxidase-mediated aerobic and anaerobic oxidations of 3-alkylindoles
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Little is known about the HRP-mediated oxidations of 3-alkylindoles. Whereas 3-methylindole and 3-ethylindole were found to be turned over smoothly by HRP, reactions of tryptophol and N-acetyltryptamine were inefficient. Oxidations of the former two indoles by HRP under aerobic conditions led to the corresponding ring-opened o-acylformanilides and oxindoles, whereas anaerobic oxidations resulted in oxidative dimerization. The major products of anaerobic oxidation of 3-methylindole were shown to be two hydrated dimers, while anhydrodimers were obtained in the 3-ethyl case. The proposed mechanism involves HRP-mediated one-electron oxidation to give an indole radical that either dimerizes (anaerobic conditions) or reacts with O2 (aerobic conditions). Measured kinetics of indole oxidation by HRP compounds I and II mirrored their relative reactivities under turnover conditions. The observed comparable binding affinities for all four indole substrates investigated suggest that the low reactivity of tryptophol and N-acetyltryptamine reflect binding to HRP in an orientation that is disadvantageous to electron transfer oxidation of the indole ring.
- Ling, Ke-Qing,Sayre, Lawrence M.
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p. 3543 - 3551
(2007/10/03)
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- New routes to oxindole derivatives
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A new, practical synthesis of the antirheumatic oxindole derivative, tenidap, has been elaborated. The new approach has initiated studies on the mechanism of the acylation reactions of oxindoles. Methods have been developed for the synthesis of 1-[alkoxy(or aryloxy)carbonyl]- and 1,3-di[alkoxy(or aryloxy)carbonyl]oxindoles starting from oxindoles. The route designed for tenidap has provided a facile access to several analogues, too. On another front, new reaction conditions are described, which turn Wenkert's synthesis of 3-alkyloxindoles (by Raney nickel induced alkylation of oxindoles with alcohols) into a highly efficient synthetic tool. The method has been extended to the synthesis of 3-alkyloxindoles from isatins and to the preparation of 3-(ω-hydroxyalkyl)oxindoles from oxindoles and isatins. Springer-Verlag 2004.
- Porcs-Makkay, Marta,Volk, Balazs,Kapiller-Dezsoefi, Rita,Mezei, Tibor,Simig, Gyula
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p. 697 - 711
(2007/10/03)
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- New One-Pot Synthesis of 3-Alkyl- and 3-(ω-Hydroxyalkyl)oxindoles from Isatins
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A new and efficient one-pot procedure has been developed for the synthesis of 3-alkyl- and 3-(ω-hydroxyalkyl)oxindoles from isatins by treatment with alcohols and diols in the presence of Raney nickel, under hydrogen atmosphere. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Volk, Balazs,Simig, Gyula
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p. 3991 - 3996
(2007/10/03)
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- Thio-oxindole derivatives
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This invention relates to compounds which are agonists of the progesterone receptor which have the general structures: wherein: R1and R2are H, alkyl, substituted alkyl; OH; O(alkyl); O(substituted alkyl); OAc; aryl; substituted aryl; heteroaryl; substituted heteroaryl; alkylaryl; alkylheteroaryl;1-propynyl; or3-propynyl; or R1and R2are joined to form an alkyl, alkenyl or heterocyclic ring; or R1and R2together comprise a double bond to CMe2; C(cycloalkyl), O, or C(cycloether); R3is H, OH, NH2, C1to C6alkyl, substituted C1to C6alkyl, C3to C6alkenyl, alkynyl, substituted alkynyl, or CORA; RAis H, C1to C3alkyl, substituted C1to C3alkyl, C1to C3alkoxy, substituted C1to C3alkoxy, C1to C3aminoalkyl, or substituted C1to C3aminoalkyl; R4is H, halogen, CN, NH2, NO2, C1to C6alkyl, or substituted C1to C6alkyl, C1to C6alkoxy, substituted C1to C6alkoxy, C1to C6aminoalkyl, or substituted C1to C6aminoalkyl; R5is optionally substituted and selected from a benzene ring, a five or six membered heterocyclic ring with 1, 2, or 3 heteroatoms selected from O, S, SO, SO2or NR6; or an indol-4-yl, indol-7-yl or benzo-2-thiophene moiety; Q1is S, NR7, CR8R9; or a pharmaceutically acceptable salt thereof, as well as methods of using these compounds to induce contraception or treat progesterone-related carcinomas and adenocarcinomas.
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-
Page column 56-57
(2010/11/30)
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- New progesterone receptor antagonists: 3,3-disubstituted-5-aryloxindoles.
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A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this comm
- Fensome, Andrew,Bender, Reinhold,Cohen, Jeffrey,Collins, Mark A,Mackner, Valerie A,Miller, Lori L,Ullrich, John W,Winneker, Richard,Wrobel, Jay,Zhang, Puwen,Zhang, Zhiming,Zhu, Yuan
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p. 3487 - 3490
(2007/10/03)
-
- Raney nickel-induced 3-alkylation of oxindole with alcohols and diols
-
New reaction conditions are described, which turn Wenkert's synthesis of 3-alkyloxindoles (Raney nickel-induced alkylation of oxindole with alcohols) into a reproducible and highly efficient synthetic tool. The method is also extended to the preparation o
- Volk, Balázs,Mezei, Tibor,Simig, Gyula
-
p. 595 - 597
(2007/10/03)
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- Regioselective palladium(II)-catalyzed synthesis of five- or seven-membered ring lactones and five-, six- or seven-membered ring lactams by cyclocarbonylation methodology
-
2-Allylphenols react with carbon monoxide and hydrogen in the presence of catalytic quantities of a cationic palladium(II) complex [(PCy3)2Pd(H)(H2O)]+BF4- or palladium acetate and 1,4-bis(diphenylpho
- El Ali, Bassam,Okuro, Kazumi,Vasapollo, Giuseppe,Alper, Howard
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p. 4264 - 4270
(2007/10/03)
-