- Divergent Coupling of Benzocyclobutenones with Indoles via C?H and C?C Activations
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Highly selective divergent coupling reactions of benzocyclobutenones and indoles, in which the chemoselectivity is controlled by catalysts, are reported herein. The substrates undergo C2(indole)–C8(benzocyclobutenone) coupling to produce benzylated indoles and benzo[b]carbazoles in the Ni- and Ru-catalyzed reactions. A completely different selectivity pattern C2(indole)–C2(benzocyclobutenone) coupling to form arylated indoles is observed in the Rh-catalyzed reaction. Preliminary mechanistic studies suggest C?H and C?C activations in the reaction pathway. Synthetic utility of this protocol is demonstrated by the selective synthesis of three different types of carbazoles from the representative products.
- Bai, Jin-Hua,Lu, Hong,Wei, Hao,Xu, Peng-Fei,Ye, Dan,Zhao, Tian-Tian
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Read Online
- One-Pot Asymmetric Oxidative Dearomatization of 2-Substituted Indoles by Merging Transition Metal Catalysis with Organocatalysis to Access C2-Tetrasubstituted Indolin-3-Ones
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A one-pot approach for the asymmetric synthesis of C2-tetrasubstituted indolin-3-ones from 2-substituted indoles was developed via merging transition metal catalysis with organocatalysis. This strategy involves two processes, including CuI catalyzed oxidative dearomatization of 2-substituted indoles using O2 as green oxidant, and followed by an proline-promoted asymmetric Mannich reaction with ketones or aldehydes. A series of C2-tetrasubstituted indolin-3-ones were obtained in 35–86% yields, 2:1->20:1 dr and 48–99% ee. Moreover, the synthetic 2-tetrasubstituted indolin-3-ones could be easily transformed into 1H-[1,3] oxazino [3,4-a]indol-5(3H)-ones via a [4+1] cyclization process. In addition, the synthetic compound 3 s show certain antibacterial activity against S. aureus ATCC25923 and multi-drug resistance bacterial strain of S. aureus (20151027077) and its MIC values up to 8 μg/mL and 16 μg/mL, respectively. (Figure presented.).
- Zhao, Yong-Long,An, Jian-Xiong,Yang, Fen-Fen,Guan, Xiang,Fu, Xiao-Zhong,Li, Zong-Qin,Wang, Da-Peng,Zhou, Meng,Yang, Yuan-Yong,He, Bin
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supporting information
p. 1277 - 1285
(2022/03/14)
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- Pd/β-cyclodextrin-catalyzed C-H functionalization in water: A greener approach to regioselective arylation of (NH)-indoles with aryl bromides
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A greener and more practical strategy for the site-selective C-H arylation of (NH)-indoles via coupling of (hetero)aryl bromides was developed, in which β-cyclodextrin, acting as both a ligand for Na2PdCl4 and a host for indoles, enables the reactions to occur easily in water. The key advantage of this method is the ingenious merging of aqueous homogeneous catalysis and ligand mediation, leading to the highly regioselective formation of C3-arylindoles with a broad substrate scope and functional-group tolerance. Moreover, the regioselectivity can be switched from the C3 to the C2-position by varying the nature of the base without recourse to employing ArI as substrates.
- Duan, Xin Hong,Xu, Peng
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supporting information
p. 19425 - 19431
(2021/11/09)
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- Iminyl-radicals by electrochemical decarboxylation of α-imino-oxy acids: construction of indole-fused polycyclics
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Iminyl radicals are reactive intermediates that can be used for the construction of various valuable heterocycles. Herein, the electrochemical decarboxylation of α-imino-oxy acids for the generation of iminyl radicals has been accomplished under exogenous-oxidant- and metal-free conditions through the use ofnBu4NBr as a mediator. The resulting iminyl radicals undergo intramolecular cyclization smoothly with the adjacent (hetero)arenes to afford a series of indole-fused polycyclic compounds.
- Wan, Jin-Lin,Cui, Jian-Feng,Zhong, Wei-Qiang,Huang, Jing-Mei
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supporting information
p. 10242 - 10245
(2021/10/12)
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- Iron-catalysed radical cyclization to synthesize germanium-substituted indolo[2,1-a]isoquinolin-6(5H)-ones and indolin-2-ones
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A simple and efficient strategy for iron-catalysed cascade radical cyclization was developed, by which an array of germanium-substituted indolo[2,1-a]isoquinolin-6(5H)-ones and indolin-2-ones were obtained in one pot with germanium hydrides as radical precursors. A rapid intramolecular radical trapping mode enabled the selective arylgermylation of alkenes over the prevalent hydrogermylation reaction.
- Luo, Yani,Tian, Tian,Nishihara, Yasushi,Lv, Leiyang,Li, Zhiping
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p. 9276 - 9279
(2021/09/20)
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- Aniline-initiated and Br?nsted acid-catalyzed one-pot reaction toward 2-aryl-3-sulfenylindoles by using α-aminocarbonyl compounds and primary amines with RSSR
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A highly novel method of direct synthesis of 2-aryl-3-sulfenylindoles in moderate to good yields was developed via one-pot tandem reaction of readily available α-aminocarbonyl compounds and catalytic amount of benzenamines with RSSR.
- Chen, De,Cheng, Chaozhihui,Deng, Wei,Guan, Wenjian,Liu, Yuxuan,Luo, Yongyue,Xiang, Jiannan,Zhang, Jiajia
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- Regioselective Direct C2 Arylation of Indole, Benzothiophene and Benzofuran: Utilization of Reusable Pd NPs and NHC-Pd@MNPs Catalyst for C–H Activation Reaction
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Abstract: A regioselective C2 arylation of indoles, benzothiophene and benzofuran without directing group has been accomplished using economically cheap Pd NPs and NHC-Pd@MNPs catalyst. The reusable catalyst is efficiently employed to access C2 arylated heterocycles in good to excellent yield. The reusability of the catalyst is studied up to five cycles and a gram-scale synthesis has been achieved. The reaction mechanism is well supported by control experiments and literature precedents. Grapic Abstract: [Figure not available: see fulltext.]
- Hegde, Rajeev V.,Ong, Tiow-Gan,Ambre, Ram,Jadhav, Arvind H.,Patil, Siddappa A.,Dateer, Ramesh B.
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p. 1397 - 1405
(2020/10/02)
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- An iron(iii)-catalyzed dehydrogenative cross-coupling reaction of indoles with benzylamines to prepare 3-aminoindole derivatives
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We report a green cascade approach to prepare a variety of 3-aminoindole derivatives in good to excellent yields through an iron(iii)-catalyzed dehydrogenative cross-coupling reaction of 2-arylindoles and primary benzylamines under mild reaction conditions. Mechanistic studies show that a cascade reaction involves a tert-butyl nitrite (TBN)-mediated nitrosation of 2-substituted indoles and a 1,5-hydrogen shift to afford indolenine oximes, sequential iron(iii)-catalyzed condensation and a 1,5-hydrogen shift over four steps in a one-pot reaction. The reaction shows a broad substrate scope of indoles and benzylamines and tolerates a wide range of functional groups. Moreover, the reaction is easily performed at the gram scale without producing waste after the reaction is completed. The 3-aminoindole product is purified by simple extraction, washing, and recrystallization without flash column chromatography. A double imine ligand containing the 3-aminoindole unit is facile to obtain in a 52% yield in one step. The present method highlights readily available starting materials, a simple purification procedure, and the usage of cheap, nontoxic, and environmentally benign iron(iii) catalysts. This journal is
- Chen, Wei-Li,Li, Kun,Liang, Cui,Liang, Wang-Fu,Liao, Wei-Cong,Mo, Dong-Liang,Qiu, Pei-Wen,Su, Gui-Fa
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p. 9610 - 9616
(2021/12/09)
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- Chiral Br?nsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles
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A new chiral Br?nsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This “designer acid catalyst”, which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.
- Yang, Kai,Lou, Yixian,Wang, Chenglan,Qi, Liang-Wen,Fang, Tongchang,Zhang, Feng,Xu, Hetao,Zhou, Lu,Li, Wangyang,Zhang, Guan,Yu, Peiyuan,Song, Qiuling
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p. 3294 - 3299
(2020/01/21)
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- Pd-catalyzed C–H bond activation of Indoles for Suzuki reaction
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Abstract: We present a practical method for Suzuki coupling by which unprotected or N-protected indoles may be selectively arylated in the C2-position through direct C–H bond activation by electrophilic Pd(TFA) 2 catalyst. The protocol is operationally simple as it is carried out in dioxane/water mixture, and air as the sole oxidant at room temperature. Various 2-arylated indoles were obtained in good yields. The protocol works for benzofuran, pyrrole and thiophene also. Graphic abstract: Selective C-2 arylation of heterocycles using Pd(II) catalyst via C–H activation was performed under ambient condition. C3–C2 migration of organopalladium intermediate controls the reaction pathway.[Figure not available: see fulltext.].
- Banerjee, Isita,Ghosh, Keshab Ch,Sinha, Surajit
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- Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C-C Bond Cleavage of 2-Arylindoles
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A variety of 2-aminobenzonitriles were prepared from 2-arylindoles in good to excellent yields through tert-butylnitrite (TBN)-mediated nitrosation and sequential iron(III)-catalyzed C-C Bond cleavage in a one-pot fashion. The 2-aminobenzonitriles can be used to rapidly synthesize benzoxazinones by intramolecular condensation. The present method features an inexpensive iron(III) catalyst, gram scalable preparations, and novel C-C bond cleavage of indoles.
- Chen, Wei-Li,Wu, Si-Yi,Mo, Xue-Ling,Wei, Liu-Xu,Liang, Cui,Mo, Dong-Liang
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p. 3527 - 3530
(2018/06/26)
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- Synthesis method of nitrogenous medicine intermediate indole derivative
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The invention relates to a synthesis method of an indole derivative shown by a nitrogenous medicine intermediate (III). The method comprises the following steps of in a solvent and in the insert gas atmosphere, under the existence of catalysts, nitrogenous ligands and acid promoters, a compound shown by a formula (I) and a compound shown by a formula (II) take a reaction; after the reaction is completed, post treatment is performed, so that a compound shown by the formula (III) is obtained. The formulas (I), (II) and (III) are shown as the accompanying drawing, wherein the R1 is selected from H or halogen; the R2 is selected from H, C1-C6 alkyls, C1-C6 alkoxy or halogen; or R2 and the substituted phenyl jointly form naphthyl. The method has the advantages that through the comprehensive selection and cooperation of the proper substrates, catalysts, nitrogenous ligands, acid promoters, solvents and the like, the range of the substrates is expanded; the aryl-substituted indol compound can be obtained at a good yield, so that the good application prospects and study values are realized in the field of organic chemical synthesis. The fire-new method is provided for the synthesis of the compounds of the kind.
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Paragraph 0055; 0056; 0057; 0058; 0059; 0071; 0072-0096
(2017/07/21)
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- Palladium-catalyzed tandem addition/cyclization in aqueous medium: Synthesis of 2-arylindoles
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An efficient protocol to construct 2-arylindoles was developed through palladium-catalyzed tandem addition/cyclization of potassium aryltrifluoroborates with aliphatic nitriles in aqueous medium. The use of water as the reaction medium makes the synthesis process environmentally benign. A plausible mechanism for the formation of 2-arylindoles involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed. Moreover, the utility of this catalytic tandem transformation was also demonstrated in an efficient gram-scale synthesis. This method provides an alternative synthetic tool for accessing a more diverse array of 2-arylindoles.
- Yu, Shuling,Hu, Kun,Gong, Julin,Qi, Linjun,Zhu, Jianghe,Zhang, Yetong,Cheng, Tianxing,Chen, Jiuxi
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p. 4300 - 4307
(2017/07/10)
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- The Development of a Palladium-Catalyzed Tandem Addition/Cyclization for the Construction of Indole Skeletons
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A palladium-catalyzed tandem addition/cyclization of 2-(2-aminoaryl)acetonitriles with arylboronic acids has been developed for the first time, achieving a new strategy for direct construction of indole skeletons. This system shows good functional group tolerance and remarkable chemoselectivity. In particular, the halogen (e.g., bromo and iodo) substituents are amenable to further synthetic elaborations thereby broadening the diversity of the products. Preliminary mechanistic experiments indicate that this transformation involves sequential nucleophilic addition followed by an intramolecular cyclization.
- Yu, Shuling,Qi, Linjun,Hu, Kun,Gong, Julin,Cheng, Tianxing,Wang, Qingzong,Chen, Jiuxi,Wu, Huayue
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p. 3631 - 3638
(2017/04/11)
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- Mild and selective base-free C-H arylation of heteroarenes: experiment and computation
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A mild and selective C-H arylation strategy for indoles, benzofurans and benzothiophenes is described. The arylation method engages aryldiazonium salts as arylating reagents in equimolar amounts. The protocol is operationally simple, base free, moisture tolerant and air tolerant. It utilizes low palladium loadings (0.5 to 2.0 mol% Pd), short reaction times, green solvents (EtOAc/2-MeTHF or MeOH) and is carried out at room temperature, providing a broad substrate scope (47 examples) and excellent selectivity (C-2 arylation for indoles and benzofurans, C-3 arylation for benzothiophenes). Mechanistic experiments and DFT calculations support a Heck-Matsuda type coupling mechanism.
- Gemoets, Hannes P. L.,Kalvet, Indrek,Nyuchev, Alexander V.,Erdmann, Nico,Hessel, Volker,Schoenebeck, Franziska,No?l, Timothy
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p. 1046 - 1055
(2017/02/10)
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- Structure-activity relationships and docking studies of synthetic 2-arylindole derivatives determined with aromatase and quinone reductase 1
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In our ongoing effort of discovering anticancer and chemopreventive agents, a series of 2-arylindole derivatives were synthesized and evaluated toward aromatase and quinone reductase 1 (QR1). Biological evaluation revealed that several compounds (e.g., 2d, IC50 = 1.61 μM; 21, IC50 = 3.05 μM; and 27, IC50 = 3.34 μM) showed aromatase inhibitory activity with half maximal inhibitory concentration (IC50) values in the low micromolar concentrations. With regard to the QR1 induction activity, 11 exhibited the highest QR1 induction ratio (IR) with a low concentration to double activity (CD) value (IR = 8.34, CD = 2.75 μM), while 7 showed the most potent CD value of 1.12 μM. A dual acting compound 24 showed aromatase inhibition (IC50 = 9.00 μM) as well as QR1 induction (CD = 5.76 μM) activities. Computational docking studies using CDOCKER (Discovery Studio 3.5) provided insight in regard to the potential binding modes of 2-arylindoles within the aromatase active site. Predominantly, the 2-arylindoles preferred binding with the 2-aryl group toward a small hydrophobic pocket within the active site. The C-5 electron withdrawing group on indole was predicted to have an important role and formed a hydrogen bond with Ser478 (OH). Alternatively, meta-pyridyl analogs may orient with the pyridyl 3′-nitrogen coordinating with the heme group.
- Prior, Allan M.,Yu, Xufen,Park, Eun-Jung,Kondratyuk, Tamara P.,Lin, Yan,Pezzuto, John M.,Sun, Dianqing
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p. 5393 - 5399
(2017/11/20)
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- Commercial Supported Gold Nanoparticles Catalyzed Alkyne Hydroamination and Indole Synthesis
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Commercial gold nanoparticles supported on titanium dioxide (TiO2) were found to be a highly efficient catalyst for alkyne hydroamination. Terminal alkynes could easily undergo intermolecular hydroamination with low catalyst loadings (0.2 mol% Au) under solvent-free conditions. Indoles were efficiently synthesized using microwave heating through intramolecular hydroamination. (Figure presented.).
- Liang, Shengzong,Hammond, Luisa,Xu, Bo,Hammond, Gerald B.
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supporting information
p. 3313 - 3318
(2016/10/21)
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- Enantioselective arylative dearomatization of indoles via pd-catalyzed intramolecular reductive heck reactions
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A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).
- Shen, Chong,Liu, Ren-Rong,Fan, Ren-Jie,Li, Ying-Long,Xu, Teng-Fei,Gao, Jian-Rong,Jia, Yi-Xia
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supporting information
p. 4936 - 4939
(2015/05/05)
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- Microwave-accelerated Pd-catalyzed desulfitative direct C2-arylation of free (NH)-indoles with arylsulfinic acids
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The rapid and efficient direct C2-arylation of free (NH)-indoles with arylsulfinic acids proceeded through a microwave-accelerated palladium-catalyzed desulfitation reaction. By using PdCl2 as a catalyst, silver acetate as an oxidant, and H2SO4 as an additive, arylsulfinic acids with both electron-donating and electron-withdrawing groups underwent desulfitative coupling with an array of free (NH)-indoles, thereby selectively providing C2-arylindoles in good yields. From C2 shining sea: The direct C2-arylation of free (NH)-indoles with arylsulfinic acids proceeded through a Pd-catalyzed desulfitation reaction. In the presence of an oxidant and an additive, 2-arylindoles were selectively afforded in good yields. Copyright
- Miao, Tao,Li, Pinhua,Wang, Guan-Wu,Wang, Lei
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p. 3185 - 3190
(2014/01/06)
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- Synthesis of indoles: Sulfur-assisted reaction of 2-nitrostilbenes with carbon monoxide
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When 2-nitrostilbenes were treated with carbon monoxide in the presence of elemental sulfur, the reductive N-heterocyclization of the 2-nitrostilbenes smoothly proceeded to give the corresponding indoles in moderate to good yields.
- Umeda, Rui,Nishimoto, Yuuta,Mashino, Tsukasa,Nishiyama, Yutaka
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p. 1241 - 1247
(2013/07/19)
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- Synthesis of 2-arylindole derivatives and evaluation as nitric oxide synthase and NFκB inhibitors
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Development of small molecule drug-like inhibitors blocking both nitric oxide synthase and NFκB could offer a synergistic therapeutic approach in the prevention and treatment of inflammation and cancer. During the course of evaluating the biological potential of a commercial compound library, 2-phenylindole (1) displayed inhibitory activity against nitrite production and NFκB with IC50 values of 38.1 ± 1.8 and 25.4 ± 2.1 μM, respectively. Based on this lead, synthesis and systematic optimization have been undertaken in an effort to find novel and more potent nitric oxide synthase and NFκB inhibitors with antiinflammatory and cancer preventive potential. First, chemical derivatizations of 1 and 2-phenylindole-3-carboxaldehyde (4) were performed to generate a panel of N-alkylated indoles and 3-oxime derivatives 2-7. Second, a series of diversified 2-arylindole derivatives (10) were synthesized from an array of substituted 2-iodoanilines (8) and terminal alkynes (9) by applying a one-pot palladium catalyzed Sonogashira-type alkynylation and base-assisted cycloaddition. Subsequent biological evaluations revealed 3-carboxaldehyde oxime and cyano substituted 2-phenylindoles 5 and 7 exhibited the strongest nitrite inhibitory activities (IC50 = 4.4 ± 0.5 and 4.8 ± 0.4 μM, respectively); as well as NFκB inhibition (IC50 = 6.9 ± 0.8 and 8.5 ± 2.0 μM, respectively). In addition, the 6′-MeO-naphthalen-2′-yl indole derivative 10at displayed excellent inhibitory activity against NFκB with an IC50 value of 0.6 ± 0.2 μM.
- Yu, Xufen,Park, Eun-Jung,Kondratyuk, Tamara P.,Pezzuto, John M.,Sun, Dianqing
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p. 8835 - 8847
(2013/01/15)
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- Pd-Catalyzed cascade reaction for the synthesis of 2-substituted indoles
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An efficient cascade methodology toward the synthesis of 2-substituted indoles has been developed. The transformation proceeds via a palladium-catalyzed cross-coupling reaction of o-nitrobenzyl cyanides with boronic acids. The use of Fe as co-catalyst during the course of reaction employs significant enhancement in reaction rates. The developed protocol allows for the unprecedented use of arylboronic acids as coupling partners for constructing 2-substituted indoles.
- Jadhav, Jagannath,Gaikwad, Vipul,Kurane, Rajanikant,Salunkhe, Rajashri,Rashinkar, Gajanan
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p. 2511 - 2515,5
(2012/12/11)
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- Pd-Catalyzed cascade reaction for the synthesis of 2-substituted indoles
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An efficient cascade methodology toward the synthesis of 2-substituted indoles has been developed. The transformation proceeds via a palladium-catalyzed cross-coupling reaction of o-nitrobenzyl cyanides with boronic acids. The use of Fe as co-catalyst during the course of reaction employs significant enhancement in reaction rates. The developed protocol allows for the unprecedented use of arylboronic acids as coupling partners for constructing 2-substituted indoles. Georg Thieme Verlag Stuttgart · New York.
- Jadhav, Jagannath,Gaikwad, Vipul,Kurane, Rajanikant,Salunkhe, Rajashri,Rashinkar, Gajanan
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p. 2511 - 2515
(2013/01/13)
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- A C-H borylation approach to suzuki-miyaura coupling of typically unstable 2-heteroaryl and polyfluorophenyl boronates
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A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used in situ. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids.
- Robbins, Daniel W.,Hartwig, John F.
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supporting information; experimental part
p. 4266 - 4269
(2012/10/08)
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- Enantioselective N-H functionalization of indoles with α,β- unsaturated γ-lactams catalyzed by chiral Bronsted acids
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Nitrogen revives: Cyclic N-acyliminium ions were generated from α,β-unsaturated γ-lactams (1) and underwent intermolecular addition by indole nucleophiles (2) under the catalysis of a chiral Bronsted acid (3). A variety of N-functionalized indole derivatives containing a pyrrolidinone moiety (4) were assembled with high enantioselectivity. Bn=benzyl. Copyright
- Xie, Yinjun,Zhao, Yingwei,Qian, Bo,Yang, Lei,Xia, Chungu,Huang, Hanmin
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supporting information; experimental part
p. 5682 - 5686
(2011/08/03)
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- Synthesis of binuclear iridium(III) and rhodium(III) complexes bearing methylnaphthalene-linked N-heterocyclic carbenes, and application to intramolecular hydroamination
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New methylnaphthalene-linked imidazolium salts 1 were synthesized through the reaction of 1,8-dibromomethylnaphthalene and N-alkylimidazole. On treatment of imidazolium salt 1 with silver oxide followed by [CpMCl2] 2 (M = Ir, Rh), binuclear iridium and rhodium complexes 2 were formed. Reaction of these complexes 2 with AgPF6 afforded Cl-bridged cationic binuclear iridium and rhodium complexes 3. X-ray crystallographic analysis of 3 revealed that the two imidazole rings of the carbene ligand are in a parallel geometry. The cationic binuclear iridium complexes 3-Ir could be applied to the intramolecular hydroamination reaction of 2-ethynylaniline to give the corresponding indole compound.
- Ogata, Kenichi,Nagaya, Toshinori,Fukuzawa, Shin-Ichi
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experimental part
p. 1675 - 1681
(2010/09/05)
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- The synthesis of 2- and 3-aryl indoles and 1,3,4,5-tetrahydropyrano[4,3-b]indoles and their antibacterial and antifungal activity
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A series of 2- and 3-aryl substituted indoles and two 1,3,4,5-tetrahydropyrano[4,3-b]indoles were synthesized from indole and 5-methoxyindole. The 2-aryl indoles were synthesized from the 1-(phenylsulfonyl)indole derivatives using magnesiation followed by iodination. The 2-iodinated compounds were then subjected to Suzuki-Miyaura reactions. In addition, the 3-aryl indoles were made from the corresponding 3-bromoindoles using Suzuki-Miyaura reactions. The 1,3,4,5-tetrahydropyrano[4,3-b]indoles were also synthesized from 1-(phenylsulfonyl)indole by magnesiation followed by treatment with allylbromide. The product was then converted into [2-allyl-1-(phenylsulfonyl)-1H-indol-3-yl]methanol which upon exposure to Hg(OAc)2 and NaBH4 afforded tetrahydropyrano[4,3-b]indoles. A number of the 2- and 3-aryl indoles displayed noteworthy antimicrobial activity, with compound 13a displaying the most significant activity (3.9 μg/mL) against the Gram-positive micro-organism Bacillus cereus.
- Leboho, Tlabo C.,Michael, Joseph P.,van Otterlo, Willem A.L.,van Vuuren, Sandy F.,de Koning, Charles B.
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scheme or table
p. 4948 - 4951
(2009/12/24)
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- Palladium-catalyzed direct arylation of (hetero) arenes with aryl boronic acids
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(Chemical Equation Presented) No compass required: A method is described for forming biaryl C-C bonds by a PdII-catalyzed cross-coupling of aryl C-H bonds with aryl boronic acids under mild conditions without the presence of directing groups. Different substituents on both (hetero)arenes and aryl boronic acids are compatible with the reaction conditions, and the homocoupling of boronic acids is highly inhibited. Dioxygen was applied as the final oxidant.
- Yang, Shang-Dong,Sun, Chang-Liang,Fang, Zhao,Li, Bi-Jie,Li, Yi-Zhou,Shi, Zhang-Jie
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p. 1473 - 1476
(2008/12/22)
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- Palladium-catalyzed direct C-2 arylation of indoles with potassium aryltrifluoroborate salts
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(Chemical Equation Presented) Mild conditions have been developed to achieve Pd(OAc)2-catalyzed regioselective cross-coupling between indoles and potassium aryltrifluoroarylborates in the presence of Cu(OAc) 2 in acetic acid at room temperature. A variety of potassium aryltrifluoroborates selectively undergo the direct arylation across indoles and afford 2-aryl indoles in moderate to good yields.
- Zhao, Jinlong,Zhang, Yuhong,Cheng, Kai
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scheme or table
p. 7428 - 7431
(2009/05/07)
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- Indium-catalyzed annulation of 2-aryl- and 2-heteroarylindoles with propargyl ethers: Concise synthesis and photophysical properties of diverse aryl- and heteroaryl-annulated[a]carbazoles
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Treatment of 2-aryl- and 2-heteroarylindoles with propargyl ethers in the presence of a catalytic amount of indium nonafluorobutanesulfonate [In(ONf) 3] gave aryl- and heteroaryl-annulated[a]carbazoles in good yields. The synthetically attractive feature is reflected by its applicability to a wide range of 2-aryl-and 2-heteroarylindoles. In the annulation reaction, propargyl ethers act as C3 sources (HC≡C-CH2OR). Among these, two carbon atoms are incorporated into the product as members of a newly constructed aromatic ring and the remaining carbon atom forms a methyl group on the aromatic ring, where the methyl group is always located next to the C3 position of the indole nucleus. The methyl group can be easily removed through SeO2 oxidation followed by decarbonylation with RhCl(CO)(PPh3) 2-Ph2P(CH2)3PPh2 as a catalyst. The new annulation strategy is applicable also to symmetrical dimers such as bithiophene and bifuran derivatives. Mechanistic studies suggest that the first step is addition reaction initiated by regioselective nucleophilic attack of the C3 of 2-aryl- and 2-heteroarylindoles to the internal carbon atom of the C≡C bond in propargyl ethers. The next stage is ring-closing S N2 process kicking out the alkoxy group and then aromatization via a 1,3-hydrogen shift is the final step. The two carbon-carbon bond-forming reactions achieved in one-pot contribute largely to the reduction in the number of steps for the synthesis of aryl- and heteroaryl-annulated[a]carbazoles. Furthermore, utilization of the Fischer indole synthesis for efficient supply of the substrates, 2-aryl- and 2-heteroarylindoles, is another important factor shortening the overall process. The development of the annulation with a wide substrate scope provided a unique opportunity to evaluate photophysical properties of a series of aryl- and heteroaryl-annulated[a]-carbazoles. Almost all the compounds evaluated in this study were found to emit purple to green light in the visible region. Some interesting structure-property correlations are also described.
- Tsuchimoto, Teruhisa,Matsubayashi, Hiromichi,Kaneko, Masayoshi,Nagase, Yuta,Miyamura, Takuhiro,Shirakawa, Eiji
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supporting information; experimental part
p. 15823 - 15835
(2009/05/16)
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- A highly selective tandem cross-coupling of gem-dihaloolefins for a modular, efficient synthesis of highly functionalized indoles
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(Chemical Equation Presented) A highly efficient method of indole synthesis using gem-dihalovinylaniline substrates and an organoboron reagent was developed via a Pd-catalyzed tandem intramolecular amination and an intermolecular Suzuki coupling. Aryl, alkenyl, and alkyl boron reagents are all successfully employed, making for a versatile modular approach. The reaction tolerates a variety of substitution patterns on the aniline leading to indoles with group at C2-C7. The orthogonal approach of the sequential copper- and palladium-mediated synthesis of 1,2-diarylindoles exploited the wide availability of diverse organoboron reagents.
- Fang, Yuan-Qing,Lautens, Mark
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p. 538 - 549
(2008/09/17)
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- Easily accessible and highly tunable Lndolyl phosphine ligands for suzuki-miyaura coupling of aryl chlorides
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This study describes a new class of easily accessible indolyl phosphine ligands, prepared via an efficient protocol involving Fischer indolization from readily available Phenylhydrazine and substituted acetophenones. This versatile ligand scaffold provides beneficial features, including high potential of steric and electronic tunability. The air-stable indolyl phosphines in combination with a palladium metal precursor provide highly effective catalysts for Suzuki-Miyaura coupling of unactivated aryl chlorides, and the catalyst loading down to 0.02 mol % can be achieved.
- So, Chau Ming,Lau, Chak Po,Kwong, Fuk Yee
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p. 2795 - 2798
(2008/02/05)
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- Pd-catalyzed tandem C-N/C-C coupling of gem-dihalovinyl systems: A modular synthesis of 2-substituted indoles
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(Chemical Equation Presented) 2-Substituted indoles were synthesized via a Pd-catalyzed tandem C-N/Suzuki-Miyaura coupling from readily prepared ortho-gem-dihalovinylanilines. Optimal conditions used a Pd(OAc) 2/S-Phos catalyst in the presence of K3PO 4·H2O and an organoboron reagent, which included boronic acids, esters, alkyl 9-BBN derivatives, and trialkylboranes. Yields of the desired indoles were good to excellent using low catalyst loadings (typically 1 mol %).
- Fang, Yuan-Qing,Lautens, Mark
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p. 3549 - 3552
(2007/10/03)
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- Direct palladium-catalyzed C-2 and C-3 arylation of indoles: A mechanistic rationale for regioselectivity
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We have recently developed palladium-catalyzed methods for direct arylation of indoles (and other azoles) wherein high C-2 selectivity was observed for both free (NH)-indole and (NR)-indole. To provide a rationale for the observed selectivity ("nonelectrophilic" regioselectivity), mechanistic studies were conducted, using the phenylation of 1-methylindole as a model system. The reaction order was determined for iodobenzene (zero order), indole (first order), and the catalyst (first order). These kinetic studies, together with the Hammett plot, provided a strong support for the electrophilic palladation pathway. In addition, the kinetic isotope effect (KIEH/D) was determined for both C-2 and C-3 positions. A surprisingly large value of 1.6 was found for the C-3 position where the substitution does not occur (secondary KIE), while a smaller value of 1.2 was found at C-2 (apparent primary KIE). On the basis of these findings, a mechanistic interpretation is presented that features an electrophilic palladation of indole, accompanied by a 1,2-migration of an intermediate palladium species. This paradigm was used to design new catalytic conditions for the C-3 arylation of indole. In case of free (NH)-indole, regioselectivity of the arylation reaction (C-2 versus C-3) was achieved by the choice of magnesium base.
- Lane, Benjamin S.,Brown, Meghann A.,Sames, Dalibor
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p. 8050 - 8057
(2007/10/03)
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- Palladium-catalysed synthesis of 2-substituted indoles
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2-lodoaniline reacts with ketones in dioxane under reflux in the presence of a catalytic amount of Pd(dba)2/1, 1′-bis(di-iso- propylphosphino)ferrocene along with NaOtBu to afford 2-substituted indoles regioselectively in moderate to good yield.
- Cho, Chan Sik,Kim, Jun Ho,Kim, Tae-Jeong,Shim, Sang Chul
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p. 630 - 631
(2007/10/03)
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- Selective C-arylation of free (NH)-heteroarenes via catalytic C-H bond functionalization
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A new system for palladium-catalyzed arylation of a broad spectrum of free (NH)-heteroarenes has been developed (indole, pyrrole, pyrazole, 2-phenylimidazole, imidazole, benzimidazole, and purine). Remarkable selectivity has been achieved in the presence of MgO base, providing single C-arylation products, while no N-arylation and no bis-arylation products have been detected. In the case of free imidazole, exclusive C-4 arylation may be switched to exclusive 2-arylation by the addition of CuI to the Pd/Ph3P/MgO system. When free aryl-(NH)-azoles are desired, direct arylation eliminates three steps in comparison to standard methods, including N-protection, stoichiometric metalation or halogenation, and N-deprotection. Copyright
- Sezen, Bengue,Sames, Dalibor
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p. 5274 - 5275
(2007/10/03)
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