- Potent 1,2,4-Triazino[5,6 b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis
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A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase that multiacetylates KAN and other aminoglycosides, rendering them unable to bind the bacterial ribosome. By high-throughput screening, a series of substituted 1,2,4-triazino[5,6b]indole-3-thioether molecules were identified as effective Eis inhibitors. Herein, we purchased 17 and synthesized 22 new compounds, evaluated their potency, and characterized their steady-state kinetics. Four inhibitors were found not only to inhibit Eis in vitro, but also to act as adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal structure of Eis in complex with a potent inhibitor and CoA shows that the inhibitors bind in the aminoglycoside binding site snugly inserted into a hydrophobic cavity. These inhibitors will undergo preclinical development as novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.
- Ngo, Huy X.,Green, Keith D.,Gajadeera, Chathurada S.,Willby, Melisa J.,Holbrook, Selina Y. L.,Hou, Caixia,Garzan, Atefeh,Mayhoub, Abdelrahman S.,Posey, James E.,Tsodikov, Oleg. V.,Garneau-Tsodikova, Sylvie
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- Organocatalytic Asymmetric Synthesis of Cyclic Acetals with Spirooxindole Skeleton
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An organocatalytic asymmetric synthesis of cyclic acetal with spirooxindole skeleton has been developed via a domino reaction between isatin and γ-hydroxy enones. Bifunctional squaramide catalyst with adamantyl motif was found to be the most effective for the cascade reaction. With 10 mol% of the catalyst, the desired products were obtained in 1.8:1 to 9:1 diastereo- and 86% to >99% enantioselectivities from a range of substituted isatins and γ-hydroxy enones. (Figure presented.).
- Shikari, Amit,Mandal, Koushik,Chopra, Deepak,Pan, Subhas Chandra
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supporting information
p. 58 - 63
(2021/11/09)
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- Decarboxylative Organocatalyzed Addition Reactions of Fluoroacetate Surrogates for the Synthesis of Fluorinated Oxindoles
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Fluorinated malonic acid half thioesters (F-MAHTs) were used as thioester enolate equivalents in organocatalyzed addition reactions to isatins. The products from a range of different N-protected and nonprotected isatins were obtained under mild reaction conditions in high yields and enantioselectivities. The unique reactivity of the thioester moiety enabled diverse derivatization and allowed for the straightforward access to a fluorinated analogue of the anticancer agent (S)-YK-4-279, a therapeutically active compound against Ewing's sarcoma.
- Zetschok, Dominik,Heieck, Lukas,Wennemers, Helma
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supporting information
p. 1753 - 1757
(2021/03/08)
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- Direct catalytic synthesis of β-(C3)-substituted pyrroles: A complementary addition to the Paal-Knorr reaction
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The synthesis of β-(C3)-functionalized pyrroles is a challenging task and requires a multistep protocol. An operationally simple direct catalytic synthesis of β-substituted pyrroles has been developed. This one-pot multicomponent method combined aqueous succinaldehyde as 1,4-dicarbonyl, primary amines, and isatins to access hydroxyl-oxindole β-tethered pyrroles. Direct synthesis of the β-substituted free NH-pyrrole is the central intensity of this work. DFT-calculations and preliminary mechanism investigation support the possible reaction pathway. This journal is
- Pawar, Amol Prakash,Yadav, Jyothi,Mir, Nisar Ahmad,Iype, Eldhose,Rangan, Krishnan,Anthal, Sumati,Kant, Rajni,Kumar, Indresh
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supporting information
p. 251 - 254
(2021/01/13)
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- A new asymmetric activation strategy for hydrazones as acyl anion equivalents in the bimetallic catalyzed carbonyl-ene reaction
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A new asymmetric activation strategy for hydrazones as acyl anion equivalents is developed in the bimetallic catalyzed carbonyl-ene reaction of isatins and hydrazones. Under mild conditions, optically active functionalized 3-hydroxy-2-oxindoles were furnished in up to 98% yield with up to 97% enantioselectivity. In this process, formaldehydetert-butylhydrazone which is seldom employed in asymmetric carbonyl-ene reactions accelerated by a metallic catalyst can be activated well by a Br?nsted base. A possible catalytic cycle is proposed.
- Hu, Wen-Bo,Song, Xixi,Wang, Min-Can
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p. 2055 - 2062
(2021/03/16)
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- Construction of 2-alkynyl aza-spiro[4,5]indole scaffolds: Via sequential C-H activations for modular click chemistry libraries
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Herein, we have developed a strategy of sequential C-H activations of indole to construct novel 2-alkynyl aza-spiro[4,5]indole scaffolds, which incorporated both alkyne and spiro-units into indole. Gram-scale synthesis and a one-pot, three-step synthesis demonstrated the utility of this protocol. Hybrid conjugates with an oseltamivir derivative further offered a powerful tool for the construction of a versatile spiroindole-containing library via click chemistry. This journal is
- Zhang, Jun,Wang, Mengmeng,Wang, Huiying,Xu, Hui,Chen, Junjie,Guo, Ziqiong,Ma, Biao,Ban, Shu-Rong,Dai, Hui-Xiong
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supporting information
p. 8656 - 8659
(2021/09/04)
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- Synthesis, characterization and anticancer activity of (5,1-substituted)-3-(indoline-4-(thiophene- 2-yl-methylene)-2-(p-tolyl)-2-methylene)-4,3-dihydro-1h-imidazole-5-one derivatives
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The synthesis of novel imidazole-5-one derivatives (5a-j) was allowed in a conventional method by way of Erlenmeyer and Schiff base mechanism. Compound 2a was synthesized by Erlenmeyer reaction of N-(4-methoxy benzoyl)glycine with 2-thiophene-carboxaldehyde in the presence of acetic anhydride and anhydrous sodium acetate. Finally, it undergoes dehydration reaction with Schiff bases of isatin derivatives (4a-j) to yield final compounds 5a-j. The organic potentials of the newly synthesized imidazole-5-one derivatives have been evaluated for their in vitro anticancer activity by MTT assay method. It against MCF-7 cells as comparison with doxorubicin popular drug. The synthesized compounds 5e, 5f and 5j exhibited excellent anticancer activity against MCF-7 cell lines.
- BAYYA, CHANDRAPRAKASH,MANDA, SARANGAPANI
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p. 2027 - 2032
(2021/08/24)
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- Copper-Catalyzed Asymmetric Propargylic Alkylation with Oxindoles: Diastereo- A nd Enantioselective Construction of Vicinal Tertiary and All-Carbon Quaternary Stereocenters
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A copper-catalyzed asymmetric propargylic alkylation of propargylic acetates with 3-substituted oxindoles for the stereoselective construction of vicinal tertiary and all-carbon quaternary stereocenters in a 3,3-disubstituted oxindole skeleton has been realized. The reaction proceeded smoothly under the catalysis of Cu(MeCN)4PF6combined with a chiral tridentate ferrocenyl P,N,N ligand, leading to a broad range of optically active 3,3-disubstituted oxindoles in high yields and with excellent diastereo- A nd enantioselectivities.
- Xia, Jin-Tao,Hu, Xiang-Ping
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supporting information
p. 1102 - 1107
(2020/02/15)
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- Annulation reaction of cyclic pyridinium ylides with: In situ generated azoalkenes for the construction of spirocyclic skeletons
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Two new types of cyclic pyridinium ylides were designed and further used in reactions with azoalkenes to access structurally diverse spirocyclic compounds. A range of spiropyrazoline oxindoles could be smoothly obtained in up to 99% yield via a [4 + 1] annulation process with oxindole 3-pyridinium ylides as C1 synthons. Similarly, a series of spiropyrazoline indanones could be prepared with indanone 2-pyridinium ylides as C1 synthons. This work represents the first example of cyclic pyridinium ylides as C1 synthons for the efficient construction of spirocyclic compounds.
- Quan, Bao-Xue,Yuan, Wei-Cheng,Zhang, Ming-Liang,Zhang, Xiao-Mei,Zhao, Jian-Qiang,Zhou, Ming-Qiang,Zhuo, Jun-Rui
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supporting information
p. 1886 - 1891
(2020/03/23)
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- Design, synthesis, and biological evaluation of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide conjugates as potent carbonic anhydrase I, II, IX, and XIII inhibitors
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A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (6a– 6o) was synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against the human (h) isoforms hCA I, II, XIII (cytosolic isoforms), and hCA IX (transmembrane tumor-associated isoform). The results revealed that the compounds 6a–6o exhibited Ki values in the low to medium nanomolar range against hCA II and hCA IX (Kis ranging from 7.7 nM to 41.3 nM) and higher Ki values against hCA I and hCA XIII. Compound 6i showed potent inhibition of hCA II (Ki = 7.7nM), being more effective compared to the standard inhibitor acetazolamide (AAZ) (Ki = 12.1 nM). Compounds 6b and 6d showed moderate activity against hCA XIII (Ki= 69.8 and 65.8 nM). Hence, compound 6i could be consider as potential lead candidate for the design of potent and selective hCA II inhibitors.
- Angeli, Andrea,Arifuddin, Mohammed,Biswas, Rashmita,Chinchilli, Krishna Kartheek,Korra, Laxman Naik,Supuran, Claudiu T.,Thacker, Pavitra S.
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- Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones
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In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R2 ethyl substituted 7 derivatives were found effective against viruses tested. R1 4-CF3 substituted 7d, R1 4-OCH3 substituted 7 g and R1 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV. Whereas only R1 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modeling studies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.
- ?zbil, Mehmet,Duran, Gizem Nur,Karal?, Nilgün,Sevin?li, Zekiye ?eyma
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- Transformations of N-arylpropiolamides to indoline-2,3-diones and acids via C≡C triple bond oxidative cleavage and C(sp2)–H functionalization
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A new palladium-catalyzed oxidative conversion of N-arylpropiolamides and H2O to various indoline-2,3-diones and acids through the C≡C triple bond cleavage and C(sp2)–H functionalization is described, which is promoted by a cooperative action of catalytic CuBr2, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and O2. The method provides a practical tool for transformations of alkynes by means of a C–H functionalization strategy, which enables the formation of one C–C bond and multiple C–O bonds in a single reaction with high substrates compatibility and excellent functional group tolerance.
- Zhou, Ming-Bo,Li, Yang,Ouyang, Xuan-Hui,Li, Jin-Heng
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p. 222 - 227
(2019/11/13)
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- Palladium-Catalyzed Allylation of Cyclopropyl Acetylenes with Oxindoles to Construct 1,3-Dienes
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A novel palladium-catalyzed allylic alkylation of oxindoles with cyclopropyl acetylenes has been developed. Various 1,3-diene oxindole framework bearing a quaternary stereocenter at the C3 position were synthesized straightforwardly in good to excellent yields with high regio-, and stereoselectivities. The reaction exhibited high atom economy and good functional group tolerance.
- Lu, Chuan-Jun,Yu, Xin,Chen, Yu-Ting,Song, Qing-Bao,Yang, Zhen-Ping,Wang, Hong
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p. 680 - 688
(2020/02/11)
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- Acylation of oxindoles using methyl/phenyl estersviathe mixed Claisen condensation - an access to 3-alkylideneoxindoles
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Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources,viz. methyl and phenyl esters, which acylate oxindolesviathe mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples ofortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.
- Gandhi, Thirumanavelan,Nagaraja, C. M.,Panyam, Pradeep Kumar Reddy,Rajeshwaran, Purushothaman,Sreedharan, Ramdas,Yadav, Saurabh
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supporting information
p. 3843 - 3847
(2020/06/03)
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- "on Water" Direct Organocatalytic Cyanoarylmethylation of Isatins for the Diastereoselective Synthesis of 3-Hydroxy-3-cyanomethyl Oxindoles
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An "on water" organocatalytic cyanoarylmethylation of aryl acetonitrile to isatins is developed, giving products in high yields and up to excellent diastereoselectivities. A remarkable enhancement of reaction rates and diastereoselectivities by water was observed under mild conditions. Moreover, this approach provides a highly efficient and environmentally benign access to thermodynamic 3-hydroxy-3-cyanomethyl oxindoles.
- Zhang, Yong,Luo, Liang,Ge, Jin,Yan, Su-Qiong,Peng, Yan-Xin,Liu, Ya-Ru,Liu, Jin-Xiang,Liu, Chong,Ma, Tianqiong,Luo, Hai-Qing
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p. 4000 - 4008
(2019/03/29)
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- Method for preparing N-substituted isatin derivatives
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A method for preparing isatin derivatives from substituted aniline is disclosed. The method includes subjecting substituted aniline shown as a formula II as a raw material to self-cyclization under anacid catalytic oxidation condition to prepare the isatin derivative with a high yield. The method is simple in process, simple to operate, mild in reaction condition, and short in reaction period. The derivatives are critical intermediates, and raw materials are cheap. The method is environmentally friendly, avoiding heavy metal pollution and use of a catalyst, and generating little 'three wastes'. The method is high in product yield and purity and is suitable for industrial production.
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Paragraph 0062; 0063
(2019/06/12)
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- CF 3 COOH/O 2 -Mediated Metal-Free Domino Construction of the Isatin Skeleton
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Directed by the strategy of C-H activation, an efficient construction of the isatin skeleton was developed through aerobic oxidation of glycine esters. The reactions were performed under CF 3 COOH/O 2 conditions in the absence of met
- Chen, Yongjian,Li, Jianjun,Wang, Fang,Zhang, Qiwei,Zhou, Jiadi
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supporting information
p. 1799 - 1804
(2019/09/09)
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- Palladium(II)/N-Heterocyclic Carbene Catalyzed One-Pot Sequential α-Arylation/Alkylation: Access to 3,3-Disubstituted Oxindoles
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Rationally designed fluorene-based mono- and bimetallic Pd-PEPPSI complexes were synthesized and demonstrated to be effective for the one-pot sequential α-arylation/alkylation of oxindoles. This streamlined approach offers efficient access to functionalized 3,3-disubstituted oxindoles in excellent yields (up to 89%) under mild reaction conditions.
- Reddy Panyam, Pradeep Kumar,Ugale, Bharat,Gandhi, Thirumanavelan
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supporting information
p. 7622 - 7632
(2018/06/22)
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- Cinchona-alkaloid-catalyzed enantioselective hydroxymethylation of 3-fluorooxindoles with paraformaldehyde
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Cinchona-alkaloid-catalyzed hydroxymethylation of 3-fluorooxindoles using paraformaldehyde as the C1 unit was achieved. A wide range of 3-fluorooxindoles was successfully reacted to give the corresponding 3-fluoro-3-hydroxymethyloxindoles with high efficiency and moderate to good enantioselectivity.
- Zhao, Jian-bo,Ren, Xinfeng,Zheng, Bu-quan,Ji, Jian,Qiu, Zi-bin,Li, Ya
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supporting information
p. 44 - 51
(2018/10/02)
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- Synthesis of Spiro[oxindole-3,2′-pyrrolidine] Derivatives from Benzynes and Azomethine Ylides through 1,3-Dipolar Cycloaddition Reactions
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A novel synthetic strategy employing benzyne and azomethine ylides for the construction of spiro[oxindole-3,2′-pyrrolidine] derivatives has been achieved in good yields. The ketimines obtained from the condensation of isatins with CF3CH2NH2 react with benzyne in the presence of weak bases such as TBAF or TBAT. This mild practical 1,3-dipolar cycloaddition provides an efficient route to access biologically active compounds.
- Ryu, Heesun,Seo, Jeongseob,Ko, Haye Min
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p. 14102 - 14109
(2018/11/21)
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- Oxidative Radical Cyclization of N-methyl-N-arylpropiolamide to Isatins via Cleavage of the Carbon-carbon Triple Bond
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A radical cyclization of N-methyl-N-arylpropiolamide to isatins via an oxidative cleavage of a carbon-carbon triple bond has been developed. In the presence of oxone and NaNO2, a variety of N-methyl-N-arylpropiolamides were smoothly transformed into isatins. A nitration reaction proceeded along with the oxidative cyclization; both nitrated and non-nitrated isatins were obtained in a one-pot reaction with moderate to good total yields. This is the first example for the synthesis of isatins via the oxidative radical cleavage of a carbon-carbon triple bond. (Figure presented.).
- Liao, Yan-Yan,Gao, Yong-Chao,Zheng, Wenxu,Tang, Ri-Yuan
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p. 3391 - 3400
(2018/07/31)
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- NaI-mediated divergent synthesis of isatins and isoindigoes: A new protocol enabled by an oxidation relay strategy
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A new approach for the synthesis of isatins and isoindigoes by an inexpensive and environmentally friendly NaI-mediated transformation is disclosed. The selectivity could be switched by simply varying the solvent, and isatins (using THF) and isoindigoes (using DMSO) could be obtained in moderate to excellent yields.
- Zhang, Hong-Hua,Wang, Yong-Qiang,Huang, Long-Tao,Zhu, Long-Qing,Feng, Yi-Yue,Lu, Ying-Mei,Zhao, Quan-Yi,Wang, Xue-Qiang,Wang, Zhen
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supporting information
p. 8265 - 8268
(2018/07/29)
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- Palladium-Catalyzed Oxidation of Indoles to Isatins by tert -Butyl Hydroperoxide
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The combination of a Pd catalyst and tert -butyl hydroeroxide (TBHP) is a powerful catalytic system for many types of oxidative transformations. Here, we report that a Pd/TBHP system facilitates the oxidation of indoles with a range of functionalities to give the corresponding isatin derivatives in good yields.
- Luo, Junfei,Gao, Shanshan,Ma, Yaorui,Ge, Guoping
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supporting information
p. 969 - 973
(2018/02/09)
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- Direct N-H/α,α,β,β-C(sp3)-H functionalization of piperidine via an azomethine ylide route: synthesis of spirooxindoles bearing 3-substituted oxindoles
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A protocol for the direct functionalization of N-H/α,α,β,β-C(sp3)-H of piperidine without any metal or external oxidants is reported. This reaction is promoted by 4-(trifluoromethyl)benzoic acid via an azomethine ylide intermediate. This is a simple method for the synthesis of spirooxindoles bearing 3-substituted oxindole moieties.
- Du, Yanlong,Yu, Aimin,Jia, Jiru,Zhang, Youquan,Meng, Xiangtai
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supporting information
p. 1684 - 1687
(2017/02/10)
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- Tertiary Amine-Catalyzed Difluoromethylthiolation of Morita–Baylis–Hillman Carbonates of Isatins with Zard's Trifluoromethylthiolation Reagent
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In this paper, we report that a novel tertiary amine-catalyzed [3+2] annulation between Morita–Baylis–Hillman (MBH) carbonates derived from isatins with thiocarbonyl fluoride (F2C=S) in situ generated from Zard's reagent proceeds smoothly under mild conditions, affording difluoromethylthiolated spirocyclic oxindoles in good to excellent yields. Moreover, the asymmetric variant could be realized with a modified Cinchona alkaloid, giving the desired cyclic adducts in good to excellent yields with good enantioselectivities. (Figure presented.).
- Fan, Xing,Yang, Haibin,Shi, Min
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supporting information
p. 49 - 57
(2017/01/14)
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- Palladium-catalyzed allylic alkylation with internal alkynes to construct C-C and C-N bonds in water
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A palladium-catalyzed system enabled efficient allylic alkylation with alkynes in water has been developed. This reaction presents an environmentally friendly strategy for constructing lots of allylic compounds with indolinones, ketones, amines as well as electron-rich aromatic compounds as nucleophiles. Moreover, the in situ formed arylallene intermediate adopting alkynes as starting materials omits the need for leaving groups and extra oxidants, showing high atom economy. The versatility of the developed reaction also lends itself to the incorporation of deuteriums by simply replacing H2O with D2O.
- Gao, Shang,Liu, Hao,Wu, Zijun,Yao, Hequan,Lin, Aijun
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supporting information
p. 1861 - 1865
(2017/06/09)
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- [3 + 3] Formal Cycloadditions of Nitrones from Isatins and Azaoxyallyl Cations for Construction of Spirooxindoles
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A [3 + 3] formal cycloaddition reaction between in situ formed azaoxyallyl cations and nitrones from isatins has been developed, furnishing a spectrum of spiro[1,2,4-oxadiazinan-5-one]oxindoles in good to excellent yields with excellent diastereoselectivity. This method provides direct and efficient access to potentially bioactive spirooxindoles incorporating a six-membered heterocyclic scaffold.
- Lin, Weijia,Zhan, Gu,Shi, Minglin,Du, Wei,Chen, Yingchun
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supporting information
p. 857 - 860
(2017/06/27)
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- Spiroannulation of Oxindoles via Aryne and Alkyne Incorporation: Substituent-Diverted, Transition-Metal-Free, One-Pot Access to Spirooxindoles
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A "product control via substrate design" strategy has been conceptualized and implemented to harness the potential of aryne and activated alkyne insertions into oxindoles to readily and efficiently furnish pharmacophoric indano- and cyclopentannulated spirooxindole scaffolds in an operationally straightforward, one-pot, transition-metal-free protocol.
- Samineni, Ramesh,Madapa, Jaipal,Srihari, Pabbaraja,Mehta, Goverdhan
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supporting information
p. 3119 - 3122
(2017/06/23)
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- Addition of carbamoylsilane to isatins: Highly efficient synthesis of 3-hydroxy-3-aminocarbonyl-2-oxindoles derivatives
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The first addition reaction between isatins and carbamoysilane has been developed which provides 3-hydroxy-3-aminocarbonyl-2-oxindoles core structures with excellent yields. Moreover, the reaction could undergo a one-pot synthesis process to furnish 3-hydroxy-3-aminocarbonyl-2-oxindole with gram-scale.
- Liang, Jin-Yan,Wang, Hui,Yang, Yan-Li,Shen, Shou-Jie,Chen, Jian-Xin
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supporting information
p. 2636 - 2639
(2017/06/14)
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- Accessing 1,3-Dienes via Palladium-Catalyzed Allylic Alkylation of Pronucleophiles with Skipped Enynes
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An unprecedented palladium-catalyzed allylic alkylation of pronucleophiles with unactivated skipped enynes has been developed. This method provides a straightforward access to a wide array of 1,3-dienes without the need to preinstall leaving groups or employ extra oxidants. The reaction exhibited high atom economy, good functional group tolerance, excellent regioselectivities, and scalability. With D2O as cosolvent, deuterium could be incorporated in high efficiency.
- Gao, Shang,Liu, Hao,Yang, Chi,Fu, Zhiyuan,Yao, Hequan,Lin, Aijun
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supporting information
p. 4710 - 4713
(2017/09/23)
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- Asymmetric Intermolecular Rauhut?Currier Reaction for the Construction of 3,3-Disubstituted Oxindoles with Quaternary Stereogenic Centers
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A remote cross Rauhut?Currier reaction utilizing vinyl ketones and para-quinone methides derived from isatins was realized, which was successfully catalyzed using bifunctional phosphines, furnishing chiral 3,3-disubstituted oxindoles in excellent enantioselectivities and high yields. The mechanistic studies demonstrated the key role of the alkyl hydrogen of the vinyl ketones, which conceivably interacted with the para-quinone methide carbonyl group via the hydrogen bond, offering a new insight for the design of novel asymmetric reactions. (Figure presented.).
- Wang, Hongyu,Wang, Kaiye,Man, Yunquan,Gao, Xiaonan,Yang, Limin,Ren, Yanfei,Li, Na,Tang, Bo,Zhao, Gang
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supporting information
p. 3934 - 3939
(2017/11/30)
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- Double Carbonylation Using Glyoxal (HCOCOH): A Practical Copper-Promoted Synthesis of Isatins from Primary and Secondary Anilines
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A novel double carbonylation process has been demonstrated with easily available HCOCOH (glyoxal) as the double carbonylation reagent. Simple CuCl2?2H2O (copper(II) chloride dihydrate) was used as the oxidant for this transformation. Under optimized reaction conditions, various primary and secondary anilines were double-carbonylated to afford their corresponding isatins (26 examples, up to 80% yields). (Figure presented.).
- Kuan, Suzie Hui Chin,Sun, Wei,Wang, Lu,Xia, Chungu,Tay, Meng Guan,Liu, Chao
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supporting information
p. 3484 - 3489
(2017/09/06)
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- Diversity-Oriented Synthesis of Oxacyclic Spirooxindole Derivatives through Ring-Closing Enyne Metathesis and Intramolecular Pauson–Khand (2+2+1) Cyclization of Oxindole Enynes
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An efficient approach for a reagent-based diversity-oriented synthesis (DOS) of novel fused spirooxindole scaffolds from oxindole enynes has been developed. The reaction involves a metal-catalyzed C-3 allylation/vinylation/homoallylation of N-substituted isatins which gives rise to the corresponding alcohols that can be converted into the required enynes. Further transformation to diverse complex molecular scaffolds proceeds via a subsequent ruthenium-catalyzed ring-closing enyne metathesis (RCEYM), or cobalt-catalyzed intramolecular Pauson–Khand (2+2+1) cyclization reaction (IPKR). This strategy provides a facile approach to various spirooxindole-vinyldihydropyrans/tetrahydrooxepines and spirocyclic fused cyclopentenones in good to excellent yields. (Figure presented.).
- Kandimalla, Satheeshkumar Reddy,Sabitha, Gowravaram
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supporting information
p. 3444 - 3453
(2017/09/25)
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- Cu-catalyzed oxidation of indoles to isatins
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The first example of Cu-catalyzed oxidation of indoles to isatin derivatives by the use of cheap aqueous tert-butyl peroxide as an oxidant was developed. This methodology is practically convenient and highly functional group tolerant, allowing a variety of indole derivatives to transform into the corresponding isatin derivatives in good yields.
- Luo, Junfei,Zhao, Yanchao,Xu, Xing,Zheng, Junliang,Liang, Hongze
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supporting information
p. 4591 - 4594
(2017/11/15)
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- Base-catalyzed controllable reaction of 3-ylideneoxindoles with O-Boc hydroxycarbamates for the synthesis of amidoacrylates and spiroaziridine oxindoles
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A base-catalyzed divergent reaction of 3-ylideneoxindoles with O-Boc hydroxycarbamates has been developed to provide efficient access to various amidoacrylates and spiroaziridine oxindoles with generally high yields, which should be potentially useful in drug discovery.
- Liu, Yi-Yin,Duan, Shu-Wen,Zhang, Rui,Liu, Yun-Hang,Chen, Jia-Rong,Xiao, Wen-Jing
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supporting information
p. 5224 - 5228
(2016/07/06)
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- Visible Light Photocatalytic Aerobic Oxygenation of Indoles and pH as a Chemoselective Switch
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An efficient chemodivergent strategy for visible light photocatalysis is developed. In the presence of a dicyanopyrazine-derived chromophore (DPZ) photocatalyst, aerobic photooxygenation of indoles could produce either isatins or formylformanilides in satisfactory yields by judiciously selecting inorganic salts or modulating the reaction pH. The current chemodivergent method is also effective with 2-substituted indoles, opening straightforward synthetic routes to valuable 2,2-disubstituted 3-oxindoles, formylformanilide derivatives, and benzoxazinones. Mechanistic investigations involving cyclic voltammetry studies further confirm that reaction pH influences the electrochemical properties of DPZ, thus affecting the oxidative pathway by which indoles are being transformed.
- Zhang, Chenhao,Li, Sanliang,Bure?, Filip,Lee, Richmond,Ye, Xinyi,Jiang, Zhiyong
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p. 6853 - 6860
(2016/10/18)
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- Homocoupling of 3-Halooxindole via Visible-Light Photocatalysis: A Mild Access to 3,3′-Bioxindoles
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This paper introduces a simple way to the homocoupling of tertiary halides induced by photocatalysis. This method features mild reaction conditions, excellent functional group tolerance, high yields, low photocatalyst loading and successful application to the highly sterically hindered systems. On the basis of the reaction results, a novel stable-radical-induced homocoupling reaction mechanism has been proposed.
- Jia, Wen-Liang,He, Jian,Yang, Jia-Jing,Gao, Xue-Wang,Liu, Qiang,Wu, Li-Zhu
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p. 7172 - 7181
(2016/08/30)
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- C-H Activation Relay (CHAR): An Efficient Construction of Isatin Skeleton by Aerobic Oxidation of Glycine Esters
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Directed by the strategy of C-H activation relay (CHAR), an efficient construction of isatin skeleton was developed through catalytic oxidation of glycine esters. The mechanistic study reveals that the oxidation of the relatively active C-H bonds initiated the followed activation of remote and inert C-H bonds, and an intramolecular 1,6-hydrogen shift was involved as a key step.
- Jia, Xiaodong,Zhu, Yingzu,Yuan, Yu,Zhang, Xuewen,Lü, Shiwei,Zhang, Liang,Luo, Liangliang
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p. 6033 - 6036
(2016/09/09)
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- Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies
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A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells.
- Senwar, Kishna Ram,Sharma, Pankaj,Reddy, T. Srinivasa,Jeengar, Manish Kumar,Nayak, V. Lakshma,Naidu,Kamal, Ahmed,Shankaraiah, Nagula
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p. 413 - 424
(2015/09/01)
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- Iodine-Mediated C-H Functionalization of sp, sp2, and sp3 Carbon: A Unified Multisubstrate Domino Approach for Isatin Synthesis
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(Chemical Equation Presented) Molecular iodine-promoted efficient construction of isatins from 2′-aminophenylacetylenes, 2′-aminostyrenes, and 2′-amino-β-ketoesters is developed via oxidative amidation of sp, sp2, and sp3 C-H bonds. The reaction involves consecutive iodination, Kornblum oxidation, and intramolecular amidation in a single reactor. The present method meets all of the atom and redox economy principles.
- Satish, Gandhesiri,Polu, Ashok,Ramar, Thangeswaran,Ilangovan, Andivelu
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p. 5167 - 5175
(2015/05/27)
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- Copper-catalyzed intramolecular oxidative C(sp3)-H amidation of 2-aminoacetophenones: Efficient synthesis of indoline-2,3-diones
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An efficient synthesis of diverse indoline-2,3-diones from 2-aminoacetophenones through copper-catalyzed intramolecular C(sp3)-H amidation is developed. The reaction proceeds in DMSO by using O2 as the sole oxidant to provide the desired products in moderate to good yields.
- Huang, Jinbo,Mao, Tingting,Zhu, Qiang
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p. 2878 - 2882
(2014/05/20)
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- Copper-catalyzed enantioselective Friedel-Crafts alkylation of pyrrole with isatins
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The highly enantioselective Friedel-Crafts alkylation of pyrrole with isatins catalyzed by the tridentate Schiff base/Cu catalyst was developed. Hexafluoroisopropanol (HFIP) was used as a crucial additive to improve the enantioselectivity. In the case of N-unprotected isatins, an innovative substrate slow-releasing strategy was applied by virtue of a Henry/retro-Henry reaction.
- Li, Chong,Guo, Fengfeng,Xu, Kun,Zhang, Sheng,Hu, Yanbin,Zha, Zhenggen,Wang, Zhiyong
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supporting information
p. 3192 - 3195
(2014/07/08)
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- New spiroindolinones bearing 5-chlorobenzothiazole moiety
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In this study, 5-chloro-3H-spiro-[1,3-benzothiazole-2,3'-indole]-2'(1'H)-one derivatives 3a-l were synthesized by the reaction of 1H-indole-2,3-diones 1a-l with 2-amino-4-chlorothiophenol 2 in ethanol. 3a-l were tested for their abilities to inhibit lipid peroxidation (LP), scavenge DPPH? and ABTS?+ radicals, and to reduce Fe3+ to Fe2+. Most of the tested compounds exhibited potent scavenging activities against ABTS?+ radical, reducing powers and strong inhibitory capacity on LP. 3a, 3d, 3e, 3h, 3j and 3k chosen as prototypes were evaluated in the National Cancer Institute's in vitro primary anticancer assay. The greatest growth inhibitions were observed against a non-small cell lung cancer cell line HOP-92 for R1-fluoro substituted 3d and a renal cancer cell line RXF-393 for R-chloro substituted 3e in the primary screen.
- Ermut, G?rkem,Karali, Nilgün,?zsoy, Nurten,Can, Ay?e
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p. 457 - 468
(2014/08/05)
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- AlCl3-promoted selective michael addition with allenoate and methyleneindolinone: Synthesis of spirocyclic oxindole by using allenoate as a four-carbon component building block
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The AlCl3-promoted cyclization of readily available allenoates with methyleneindolinone is disclosed. The present strategy provides a rapid access to spirocyclic oxindole-cyclohexenones in an efficient manner. Remarkably, the allenoate is implemented as a four-carbon (4C) component to form the ring, which shows high synthetic efficiency. Flexibility of this method allows quick synthesis of spirocyclic oxindole-dihydropyrans by varying one of the components. It is also noteworthy that AlCl3 serves as the chlorine source as well as an effective catalyst to facilitate this interesting transformation.
- Xu, Shibo,Li, Chunju,Jia, Xueshun,Li, Jian
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p. 11161 - 11169
(2015/01/08)
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- Synthesis of N-alkyl isatins via oxidative cyclization of N-alkyl 2-bromo(chloro)acetanilides
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A highly efficient method for the synthesis of N-alkyl isatins starting from N-alkyl 2-bromo or 2-chloro acetanilides is described. The starting materials are easy to prepare and the yields of isatins are generally high. Operationally the reaction is very simple to run. Even though best results were obtained with a catalytic amount of CuI, the reactions of N-alkyl 2-bromo acetanilides actually performed well even in the absence of any metal catalyst. the Partner Organisations 2014.
- Gui, Qingwen,Dai, Fenglin,Liu, Jidan,Chen, Peixing,Yang, Zhiyong,Chen, Xiang,Tan, Ze
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supporting information
p. 3349 - 3353
(2014/05/20)
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- Multicomponent reaction to construct spirocyclic oxindoles with a Michael (triple Michael)/cyclization cascade sequence as the key step
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Multicomponent cycloadditions with readily available isocyanides, allenoates, and isatylidene malononitriles are disclosed. This reaction, which does not require the aid of any catalyst, allows the efficient syntheses of spirocyclic oxindoles with excellent regioselectivity. Reactions with ethyl 2,3-butadienoate and various structurally diverse α- and γ-substituted allenoates are also fully explored. Remarkably, we have shown that the usual three-component process can be further developed into an unprecedented four-component cycloaddition in the presence of water, which provides a new strategy to access highly unusual tricyclic oxindoles. From a synthetic point of view, this protocol is very interesting considering the high level of complexity reached in one step. The mechanism is thought to proceed by a triple Michael/cyclization process by using allenoate as a three carbon atom component (3 C). Furthermore, multicomponent reaction with γ-substituted allenoate also results in a very interesting conversion. In such cases, the unusual cleavage of the "C=C" double bond of isatylidene malononitrile and one of the "C=C" double bonds of allenoate is always observed. Multiply your chemistry! Multicomponent reactions with readily available isocyanides, allenoates, and isatylidene malononitriles are disclosed. This protocol provides a synthetic route to an exocyclic double bond containing a spirocyclic ring in an efficient manner with excellent regioselectivity (see scheme). Copyright
- Li, Jian,Wang, Ning,Li, Chunju,Jia, Xueshun
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supporting information; experimental part
p. 9645 - 9650
(2012/09/07)
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- Isocyanide-based multicomponent [2+2+1]-cycloaddition strategy to construct functionalized spirocyclic oxindoles
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Isocyanide-based three-component [2+2+1]-cycloaddition reactions from isocyanides, activated alkynes, and isatylidene malononitriles were investigated to provide a new access to spirocyclic oxindole with five-membered carbon rings. The displacement of isatylidene malononitrile with oxindolylideneacetate essentially results in opposite regioselectivity, which adds to its attractiveness. Georg Thieme Verlag Stuttgart ? New York.
- Jie, Haohua,Li, Jian,Li, Chunju,Jia, Xueshun
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supporting information
p. 2274 - 2278
(2012/10/29)
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- Synthesis of 1-substituted 4(1H)-quinazolinones under solvent-free conditions
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(Chemical Equation Presented) Heating a mixture of 2-(N-alkylamino)benzoic acids, triethyl orthoformate, and ammonium acetate under solvent-free conditions generated 1-substituted 4(1H)- quinazolinones in 73-99% yields. Moreover, a possible reaction pathway was proposed. Copyright Taylor & Francis Group, LLC.
- Wang, Yao,Zhang, Mei,Cao, Shengli,Lin, Huihui,Gao, Man,Li, Zhongfeng
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experimental part
p. 2715 - 2727
(2012/07/14)
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- Regiospecific epoxide opening: A facile approach for the synthesis of 3-hydroxy-3-aminomethylindolin-2-one derivatives
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A mild and eco-friendly method has been developed for aminolysis of 3-oxirane-indolin-2-ones with aliphatic and aromatic amines to afford 3-hydroxy-3-aminomethylindolin-2-ones. An enhancement in reaction rate was observed when water was used as the reaction medium. The reactions proceed regiospecifically to open the epoxide ring from the less-substituted end.
- Chouhan, Mangilal,Senwar, Kishna Ram,Sharma, Ratnesh,Grover, Vikas,Nair, Vipin A.
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scheme or table
p. 2553 - 2560
(2011/10/12)
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- Triphenylphosphine-catalyzed [3+2] cycloaddition of allenoate and active olefins: Syntheses of spirooxindole derivatives
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A series of spiro compounds was achieved by triphenylphosphine-catalyzed [3+2] cycloaddition between active methylenemalononitrile and ethyl 2,3-butadienoate. Careful investigation showed that the present method had high regioselectivity. The products have a spirooxindole skeleton, which is a motif common in many natural products and pharmaceutically active compounds. Georg Thieme Verlag Stuttgart - New York.
- Guo, Shanyan,Wang, Rendong,Li, Jian,Li, Chunju,Deng, Hongmei,Jia, Xueshun
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supporting information; experimental part
p. 2256 - 2258
(2011/11/05)
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