- Direct palladium-catalyzed C-3 arylation of indoles
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An efficient protocol for palladium-catalyzed direct C-3 arylation of indoles containing unprotected heterocyclic nitrogen atom has been developed.
- Zhang, Zhiqiang,Hu, Zhizhi,Yu, Zhixiao,Lei, Peng,Chi, Haijun,Wang, Yue,He, Ren
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- Distinguishing between Homogeneous and Heterogeneous Catalytic Activity in C-H Arylation of an Indole with Aryl Halides under ligandless Conditions: Crucial Evidence from Real Catalytic Experiments
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The kinetic approach for distinguishing between homogeneous and heterogeneous catalysis mechanisms by the analysis of differential selectivity was applied for direct C-H arylation of an indole with aryl halides under ligandless conditions. The differential selectivity of competing arylation of an indole with two aryl iodides or bromides and the differential regioselectivity of a parallel formation of C2- and C3-regioisomers of arylated indoles were studied by the simple method of phase trajectories needed for raw kinetic data only. The results obtained indicated that the selectivities strongly depended on the type (soluble or insoluble) and concentration of the Pd precursor. Considering the pathways of Pd transformations under the reaction conditions, this indicates a substantial contribution of catalysis occurring on the surface of metallic Pd (including nanoparticles).
- Yarosh, Elena V.,Kurokhtina, Anna A.,Larina, Elizaveta V.,Lagoda, Nadezhda A.,Schmidt, Alexander F.
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- A facile access to substituted indoles utilizing palladium catalyzed annulation under microwave enhanced conditions
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A facile access to differently substituted indoles using palladium catalyzed annulation reactions under microwave enhanced conditions has been achieved. A highly active and efficient catalytic system PdCl 2/(A-taphos) for the synthesis of indole via palladium catalyzed ring annulation of ortho iodo anilines and aldehydes has been developed.
- Karuvalam, Ranjith P.,Haridas, Karickal R.,Sajith, Ayyiliath M.,Muralidharan, Arayambath
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- Traceless solid phase synthesis of 2,3-disubstituted indoles
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An efficient method for the traceless solid phase synthesis of 2,3- disubstituted indoles using a THP linker and a Pd(0)-mediated annulation of 2-iodoaniline and acetylenes is reported.
- Smith, Adrian L.,Stevenson, Graeme I.,Swain, Christopher J.,Castro, Jose L.
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- Mechanistic Study of Direct Arylation of Indole Using Differential Selectivity Measurements: Shedding Light on the Active Species and Revealing the Key Role of Electrophilic Substitution in the Catalytic Cycle
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Differential selectivity of the direct arylation of indole with aryl halides under competing and noncompeting conditions with a varying set of reaction parameters was determined using phase trajectories. The results described herein allow for conclusions to be drawn regarding the character of active complexes (cationic, neutral, or anionic) as well as realization of the indole electrophilic substitution in the catalytic cycle using the ligand-free catalytic system.
- Kurokhtina, Anna A.,Larina, Elizaveta V.,Yarosh, Elena V.,Lagoda, Nadezhda A.,Schmidt, Alexander F.
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- Immobilized indolylboron as a key intermediate for solid-phase synthesis of bisindole alkaloid analogs
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Immobilized indolylboron was easily prepared from resin-bound iodoindole and the subsequent Suzuki coupling reaction was used for the syntheses of bisindole alkaloid analogs.
- Kasahara, Takahiro,Kondo, Yoshinori
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- A novel and direct synthesis of indoles via catalytic reductive annulation of nitroaromatics with alkynes
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Indoles are produced regioselectively and in moderate yields from the reactions of nitroaromatics with alkynes catalyzed by [CpM(CO)2]2 (1; [(η5-C5H5)Fe(CO)2] 2; [(η5-C5Me5)-Fe(CO)2] 2; [(η5-C5Me5)Ru(CO)2] 2) under carbon monoxide.
- Penoni, Andrea,Nicholas, Kenneth M.
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- Development of Pd Supported Catalysts Using Thiol-Functionalized Mesoporous Silica Frameworks: Application to the Chemo- and Regioselective C-3 Arylation of Free-Indole
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We report here the development of Pd-supported catalysts for the selective C-3 arylation of free-indole using thiol-functionalized silica supports to anchor the palladium centers. The palladium (II) complex, Pd(OAc)2, was efficiently loaded into various thiol-functionalized mesostructured silicas at room temperature. These materials exhibit different contents of surface SH groups (0.3 to 1.8 SH/nm2) and various SH/Pd molar ratios from 6 to 65. It was found that the catalysts containing the most isolated surface SH groups (0.3 SH/nm2) and the highest loading of Pd were the most active, reaching 70 % of conversion, 1400 as turnover numbers and 100 % selectivity in the C-3 arylated product using only 0.05 mol % of Pd. However, a leaching of active Pd species (1.7 ppm) was detected. The best compromise was found for a specific solid containing isolated surface thiol groups (0.3 SH/nm2) and a very low loading of Pd (SH/Pd=65). It exhibited a high TON (608) with a very low Pd leaching of 0.5 ppm in the course of the catalytic reaction. These results thus illustrate that both surface SH sites isolation and concentration, as well as the SH/Pd molar ratio are key parameters to access high catalytic performances and very low leaching of metal during catalysis.
- Renom Carrasco, Marc,Khodja, Walid,Demarcy, Clément,Veyre, Laurent,Camp, Clément,Thieuleux, Chloé
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- Larock indole synthesis using palladium complexes immobilized onto mesoporous silica
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Heterogeneous palladium catalysts were prepared by covalent immobilization of palladium (II) complexes of the general formula PdCl2L2 (L = P, CN) onto SBA-15 silica using a post-synthetic method. The state of the hybrid materials was characterized using a wide variety of molecular and solid-state techniques. In general, all the palladium modified solids exhibited highly ordered mesostructures while keeping the integrity of the parent molecular precursors. The catalytic performances of the materials were evaluated in the heteroannulation of 2-iodoaniline and 2-bromoaniline with triethyl(phenylethynyl)silane which showed high activities and selectivities with isolated yields in the range of 80-85%. Despite a decrease in the initial activity, quantitative conversion of iodoaniline to the expected product was observed over multiple recyclings, making these materials particularly efficient for such applications. The catalytic process was shown to be homogeneous in nature, the solid apparently serving as a reservoir for the metal between cycles.
- Batail, Nelly,Bendjeriou, Anissa,Djakovitch, Laurent,Dufaud, Véronique
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- Efficient synthesis of N-methoxyindoles via alkylative cycloaddition of nitrosoarenes with alkynes
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N-Methoxyindoles are produced in moderate to excellent yields from the reaction between nitrosoarenes and alkynes in the presence of K 2CO3/(CH3)2SO4. Terminal alkynes with conjugating substituents af
- Penoni, Andrea,Palmisano, Giovanni,Broggini, Gianluigi,Kadowaki, Ayako,Nicholas, Kenneth M.
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- Synthesis of Non-Terminal Alkenyl Ethers, Alkenyl Sulfides, and N-Vinylazoles from Arylaldehydes or Diarylketones, DMSO and O, S, N-Nucleophiles
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A transition-metal-free protocol for the synthesis of non-terminal alkenyl ethers, alkenyl sulfides, and N-vinylazoles from arylaldehydes or diarylketones, DMSO and O, S, N-nucleophiles has been reported. In this protocol, 24 examples of non-terminal alkenyl ethers and 28 examples of non-terminal alkenyl sulfides in 72–95% yields have been synthesized within 5 min. Moreover, 27 examples of non-terminal N-vinylazoles with 57–88% yields have also been synthesized within 2 hours. The preliminary mechanism investigations revealed that arylaldehydes or diarylketones offered a carbon atom, DMSO provided a methine and O, S, N-nucleophiles contributed one X atom for constructing C=C?X structure. (Figure presented.).
- Nie, Zhiwen,Lv, Huifang,Yang, Tonglin,Su, Miaodong,Luo, Weiping,Liu, Qiang,Guo, Cancheng
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supporting information
p. 1473 - 1480
(2022/04/03)
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- Ir(iii)-Catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling for the synthesis of N-H indoles
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Herein, an iridium(iii)-catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling of unprotected 2-alkenyl anilines is described. The developed method allows the synthesis of a variety of 3-substituted N-H indole scaffolds under undivided electrolytic conditions. Mechanistic studies suggest that the reaction proceeds through the electro-oxidation induced reductive elimination pathway.
- Chang, Sukbok,Kim, Dongwook,Kim, Youyoung
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supporting information
p. 12309 - 12312
(2021/12/07)
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- Annulative π-Extension (APEX) of Indoles to Pyrido[1,2- a]indoles Using 4-Oxo Peroxides as C4 Units
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Annulative π-extension (APEX) of 3-substituted indoles to pyrido[1,2-a]indoles is developed by using 4-oxo peroxides as π-extending reagents, which are employed as versatile C4 building blocks. This transformation is initiated by Br?nsted acid-mediated Hock rearrangement of the peroxyl group. Notably, the pyrido[1,2-a]indole products are obtained by elimination of the indole moiety from the corresponding dihydropyrido[1,2-a]indoles, which could be selectively formed at room temperature.
- Wang, Xin,Lou, Chenhao,Lv, Leiyang,Li, Zhiping
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supporting information
p. 5978 - 5982
(2021/08/03)
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- Synthesis and antimycobacterial activity of 3-phenyl-1h-indoles
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Tuberculosis has been described as a global health crisis since the 1990s, with an estimated 1.4 million deaths in the last year. Herein, a series of 20 1H-indoles were synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (Mtb) g
- Abbadi, Bruno Lopes,Basso, Luiz Augusto,Bizarro, Cristiano Valim,Dornelles, Maiele,Duarte, Lovaine,Etchart, Renata Jardim,Lourega, Rogério Vescia,Macchi, Fernanda Souza,Machado, Pablo,Neves, Christiano Ev,Perelló, Marcia Alberton,Rambo, Raoní S.,Silva, Fernanda Fries,Sperotto, Nathalia
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- Modular counter-Fischer?indole synthesis through radical-enolate coupling
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A single-electron transfer mediated modular indole formation reaction from a 2-iodoaniline derivative and a ketone has been developed. This transition-metal-free reaction shows a broad substrate scope and unconventional regioselectivity trends. Moreover, important functional groups for further transformation are tolerated under the reaction conditions. Density functional theory studies reveal that the reaction proceeds by metal coordination, which converts a disfavored 5-endo-trig cyclization to an accessible 7-endo-trig process.
- Chung, Hyunho,Kim, Jeongyun,Gonzalez-Montiel, Gisela A.,Cheong, Paul Ha-Yeon,Lee, Hong Geun
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supporting information
p. 1096 - 1102
(2021/01/26)
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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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- Electro-Oxidative C-N Bond Formation through Azolation of Indole Derivatives: An Access to 3-Substituent-2-(Azol-1-yl)indoles
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A practical protocol to synthesize 3-substituent-2-(azol-1-yl)indole derivatives has been developed via an electrochemical oxidative cross coupling process under mild conditions. This electro-oxidative C-N bond formation strategy tolerates a range of functional groups and is amenable to gram scale synthesis. Moreover, this method was applied to the late-stage functionalization of bioactive molecules.
- Zhou, Naifu,Zhao, Junhao,Sun, Chengbo,Lai, Yuqin,Ruan, Zhixiong,Feng, Pengju
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p. 16059 - 16067
(2021/10/01)
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- Characterization of heterogeneous aryl-Pd(ii)-oxo clusters as active species for C-H arylation
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C-H arylation with heterogeneous palladium was investigated. The surface oxidation of Pd nanoparticles with a hypervalent iodine reagent, [Ph2I]BF4, resulted in the generation of Pd(ii)-aryl-oxo clusters, which were characterized as the crucial intermediate.
- Shin, Taeil,Kim, Minjun,Jung, Younjae,Cho, Sung June,Kim, Hyunwoo,Song, Hyunjoon
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supporting information
p. 14404 - 14407
(2020/12/01)
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- Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Br?nsted Acid
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We disclose a nickel/Br?nsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.
- Kathe, Prasad M.,Caciuleanu, Alexandru,Berkefeld, Andreas,Fleischer, Ivana
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p. 15183 - 15196
(2020/11/30)
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- Monoamine Oxidase (MAO-N) Biocatalyzed Synthesis of Indoles from Indolines Prepared via Photocatalytic Cyclization/Arylative Dearomatization
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The biocatalytic aromatization of indolines into indole derivatives exploiting monoamine oxidase (MAO-N) enzymes is presented. Indoline substrates were prepared via photocatalytic cyclization of arylaniline precursors or via arylative dearomatization of unsubstituted indoles and in turn chemoselectively aromatized by the MAO-N D11 whole cell biocatalyst. Computational docking studies of the indoline substrates in the MAO-N D11 catalytic site allowed for the rationalization of the biocatalytic mechanism and experimental results of the biotransformation. This methodology represents an efficient example of biocatalytic synthesis of indole derivatives and offers a facile approach to access these aromatic heterocycles under mild reaction conditions.
- Black, Gary W.,Brancale, Andrea,Castagnolo, Daniele,Colonna, Serena,Ferla, Salvatore,Masci, Domiziana,Turner, Nicholas J.,Varricchio, Carmine,Zhao, Fei
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p. 6414 - 6421
(2020/07/09)
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- Synthesis of N-Heterocycles by Reductive Cyclization of Nitroalkenes Using Molybdenum Hexacarbonyl as Carbon Monoxide Surrogate
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The development of a method that uses molybdenum hexacarbonyl [Mo(CO)6] as carbon monoxide (CO) surrogate for the palladium-catalyzed reductive cyclization of nitroalkenes into indoles or thienopyrroles is reported. Several types of nitroalkenes could be transformed into the desired products in excellent yields and in most cases with complete regioselectivities and higher yields than those previously reported with palladium/CO system.
- Su, Zhiyou,Liu, Bo,Liao, Hongze,Lin, Hou-Wen
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p. 4059 - 4066
(2020/06/21)
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- Structure Ligation Relationship of Amino Acids for the Selective Indole C?H Arylation Reaction: L-Aspartic acid as Sustainable Alternative of Phosphine Ligands
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The Structure Ligation Relationship (SLR) of free amino acids (AAs) under Pd-catalysis were examined for the chemo- and regio-selective indole C?H arylation reactions. While the majority of AAs were minor or ineffective, the L-aspartic acid (L-Asp) stands out promising to deliver high-value C3-arylated indoles with excellent chemo- (C vs N) and regioselectivity (C3 vs C2) with high functional group tolerance. Thus, the protocol offers a cost-effective and sustainable alternative of phosphine-based ligands for the indole C3?H arylation reactions. Preliminary mechanistic investigations suggested the simultaneous involvement of ?NH2, α-CO2H, and β-CO2H functionalities of L-Asp and found critical for its ligation efficiency. The developed catalytic system was compatible with the tandem decarboxylation/arylation procedure for the chemoselective synthesis of 3-aryl indoles. (Figure presented.).
- Lokhande?, Shyam Kumar,Vaidya?, Gargi Nikhil,Satpute, Dinesh Parshuram,Venkatesh, Ashwini,Kumar, Sanjeev,Kumar, Dinesh
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p. 2857 - 2863
(2020/06/09)
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- Arylation of indoles using cyclohexanones dually-catalyzed by niobic acid and palladium-on-carbons
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3-Arylindoles were easily constructed from indoles and cyclohexanone derivatives using a combination of catalytic niobic acid-on-carbon (Nb2O5/C) and palladium-on-carbon (Pd/C) under heating conditions without any oxidants. The Lewis acidic Nb2O5/C promoted the nucleophilic addition of indoles to the cyclohexanones, and the subsequent dehydration and Pd/C-catalyzed dehydrogenation produced the 3-arylindoles. The additive 2,3-dimethyl-1,3-butadiene worked as a hydrogen acceptor to facilitate the dehydrogenation step.
- Ban, Kazuho,Sajiki, Hironao,Sawama, Yoshinari,Yamamoto, Yuta
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supporting information
p. 3898 - 3902
(2020/06/03)
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- Metal-free and regiospecific synthesis of 3-arylindoles
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A convenient, metal-free, and organic acid-base promoted synthetic method to prepare 3-arylindoles from 3-aryloxirane-2-carbonitriles and arylhydrazine hydrochlorides has been developed. In the reaction, the organic acid catalyzes a tandem nucleophilic ri
- Xie, Wenlai,Xu, Chuangchuang,Xu, Jiaxi
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p. 2661 - 2671
(2020/04/17)
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- Acid mediated coupling of aliphatic amines and nitrosoarenes to indoles
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Traditionally, amines react with nitrosoarenes to provide the corresponding imines or azo compounds. Herein, we report an acid mediated annulation reaction of aliphatic amines and nitrosoarenes to provide indole derivatives. The elusive direct annulation of aliphatic amines and nitrosoarenes via simultaneous C-C and C-N bond formation was achieved under metal free conditions. This conceptually novel method for indole synthesis does not require pre-functionalization steps for the new C-C and C-N bond formation. The method has been applied for an elegant synthesis of nor-neocryptolepine and neocryptolepine.
- Roy, Subhra Kanti,Purkait, Anisha,Aziz, Sk Md Tarik,Jana, Chandan K.
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p. 3167 - 3170
(2020/03/23)
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- Tf2O-mediated Reaction of Alkenyl Sulfoxides with Unprotected Anilines in Flow Microreactors
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Flow microreactors have allowed an efficient extended Pummerer reaction of ketene dithioacetal monoxides with anilines by precise control of unstable sulfonium intermediates and spatial separation of the generation of the intermediates and the nucleophilic attack to the intermediates. A new iodoniummediated cyclization has been devised to convert the products, thioimidates, into indoles.
- Baralle, Alexandre,Inukai, Tomoaki,Nagaki, Aiichiro,Nogi, Keisuke,Osuka, Atsuhiro,Yanagi, Tomoyuki,Yorimitsu, Hideki,Yoshida, Jun-Ichi
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p. 160 - 163
(2020/02/25)
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- Pd-Catalyzed Reductive Cyclization of Nitroarenes with CO2 as the CO Source
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A reductive amination process that constructs indoles, carbazoles or benzimidazoles from nitroarenes – irrespective of their electronic or steric nature – was developed that uses CO2 as the source of CO. The process is robust, tolerating common gaseous components of flue gas (H2S, SO2, NO and H2O) without adversely affecting the reductive cyclization.
- Guan, Xinyu,Zhu, Haoran,Zhao, Yingwei,Driver, Tom G.
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- Regiospecificity in Ligand-Free Pd-Catalyzed C-H Arylation of Indoles: LiHMDS as Base and Transient Directing Group
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A highly efficient catalyst-base pair for the C-H arylation of free (NH)-indoles in the C-3 position is reported. Ligand-free palladium acetate coupled with lithium hexamethyldisilazide (LiHMDS) catalyzed the regiospecific, i.e. 100% regioselective, C-3 a
- Camp, Clément,Canivet, Jér?me,Clot, Eric,Demarcy, Clément,Mohr, Yorck,Quadrelli, Elsje Alessandra,Renom-Carrasco, Marc,Thieuleux, Chloé,Wisser, Florian M.
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p. 2713 - 2719
(2020/03/11)
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- Iron-catalyzed reductive coupling of nitroarenes with olefins: Intermediate of iron-nitroso complex
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Using a single half-sandwich iron(II) compound, CpFe(1,2-Ph2PC6H4S)(NCMe) (Cp- = C5Me5-, 1) as a catalyst, reductive coupling of nitroarenes with olefins has been achieved by a well-defined iron(II)/(EtO)3SiH system. Through either inter- or intramolecular reductive coupling, various branched amines and indole derivatives have been directly synthesized in one-pot. Mechanistic studies showed that the catalysis is initiated by activation of nitroarenes by the iron(II) catalyst with silane, generating iron-nitrosoarene intermediate for the C-N bond coupling.
- Song, Heng,Yang, Zhuoyi,Tung, Chen-Ho,Wang, Wenguang
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p. 276 - 281
(2019/12/24)
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- Selective Oxidative Cleavage of 3-Methylindoles with Primary Amines Affording Quinazolinones
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A selective functionalization of C-C-C bonds toward N-C-O bonds is realized by an n-Bu4NI-catalyzed reaction of 3-methylindoles with primary amines using TBHP as the unique oxidant. The systematic process involves oxygenation, nitrogenation, ring-opening, and recyclization, affording a broad range of quinazolinones in good to excellent yields.
- He, Junhui,Dong, Jianyu,Su, Lebin,Wu, Shaofeng,Liu, Lixin,Yin, Shuang-Feng,Zhou, Yongbo
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supporting information
p. 2522 - 2526
(2020/04/09)
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- Heterocyclic compounds and organic light-emitting diode including the same
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The present invention relates to a novel heterocyclic compound and an organic electroluminescent device including the same as a light emitting material, specifically a heterocyclic compound denoted by chemical formula 1, and an organic electroluminescent device having excellent luminance properties including driving voltage and luminance efficiency.
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Paragraph 0288; 0325-0330
(2020/11/20)
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- Nickel-Catalyzed Asymmetric Friedel-Crafts Propargylation of 3-Substituted Indoles with Propargylic Carbonates Bearing an Internal Alkyne Group
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The nickel-catalyzed highly enantioselective Friedel-Crafts propargylation of 3-substituted indoles with propargylic carbonates bearing an internal alkyne group was developed. A wide array of the propargylic carbonates as well as 3-substituted indoles can be applicable to the asymmetric nickel catalysis, providing the corresponding chiral C-3 propargylated indolenine derivatives bearing two vicinal chiral centers in up to 89% yield with up to >99% ee and 94:6 dr (24 examples).
- Miyazaki, Yusuke,Zhou, Biao,Tsuji, Hiroaki,Kawatsura, Motoi
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supporting information
p. 2049 - 2053
(2020/03/04)
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- Organocatalytic Formal (3 + 2) Cycloaddition toward Chiral Pyrrolo[1,2- a]indoles via Dynamic Kinetic Resolution of Allene Intermediates
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We report the chiral phosphoric acid catalyzed formal (3 + 2) cycloaddition of 3-substituted 1H-indoles and propargylic alcohols containing a functional directing group (p-NHAc or p-OH). This work represents a straightforward method to synthesize chiral pyrrolo[1,2-a]indole bearing a tetrasubstituted carbon stereocenter. The reaction proceeds smoothly with a wide array of substrate tolerance to deliver various chiral pyrrolo[1,2-a]indoles in up to 93percent yield and 98percent ee. The utility of this method is highlighted by the diverse transformations of the products into various indole derivatives.
- Bai, Jian-Fei,Zhao, Lulu,Wang, Fang,Yan, Fachao,Kano, Taichi,Maruoka, Keiji,Li, Yuehui
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supporting information
p. 5439 - 5445
(2020/07/14)
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- Asymmetric N-Hydroxyalkylation of Indoles with Ethyl Glyoxalates Catalyzed by a Chiral Phosphoric Acid: Highly Enantioselective Synthesis of Chiral N,O-Aminal Indole Derivatives
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A method of SPINOL-derived chiral phosphoric acid catalyzed asymmetric intermolecular N-hydroxyalkylation of multisubstituted indoles with ethyl glyoxalates is described in this report. This protocol provides an alternative, convenient, and direct strategy for efficient access to structurally unique α-chiral indole N,O-acyclic aminals with a broad substrate scope and good to excellent enantioselectivities. The synthetic utility of this methodology is illustrated by a gram-scale experiment and the subsequent efficient synthesis of more complex chiral N,O-aminal indole derivatives.
- Wang, Le,Zhou, Jia,Ding, Tong-Mei,Yan, Zhi-Qiang,Hou, Si-Hua,Zhu, Guo-Dong,Zhang, Shu-Yu
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p. 2795 - 2799
(2019/04/30)
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- Fe(III)-Catalyzed direct C3 chalcogenylation of indole: The effect of iodide ions
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A mild and efficient iron (III)-catalyzed C3 chalcogenylation of indoles has been developed and the role of the iodide ions in this transformation was investigated. EPR experiments revealed the reduction of Fe(III) to Fe(II) under the reaction conditions, supporting the formation of molecular iodine in the system, which in effect catalyze the reaction. The scope of the chalcogenylation was broad and the synthesis of more functionalized 3-selenylindoles was explored.
- Luz, Eduardo Q.,Seckler, Diego,Araújo, Janylson Souza,Angst, Leonardo,Lima, David B.,Maluf Rios, Elise Ane,Ribeiro, Ronny R.,Rampon, Daniel S.
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supporting information
p. 1258 - 1266
(2019/02/03)
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- Iron-Promoted Construction of Indoles via Intramolecular Oxidative C-N Coupling of 2-Alkenylanilines Using Persulfate
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Indole scaffold synthesis relies primarily on oxidative C-H amination of N-protected alkenylanilines for C-N intramolecular cyclization reactions. Herein, for the first time, without N-protection, various readily prepared 2-alkenylanilines were transformed into the desired indole products in good yields by using K 2 S 2 O 8 as oxidant in the presence of catalytic amounts of FeF 2. The K 2 S 2 O 8 /FeF 2 system offers a direct and benign synthetic route to 3-arylindoles and it is applicable to a wide range of substituted indoles including drug intermediates.
- Li, Yudong,Li, Yuehui,Luo, Shuping,Wang, Menglan,Wu, Qing-An
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p. 3085 - 3090
(2019/08/07)
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- Diamines as interparticle linkers for silica-titania supported PdCu bimetallic nanoparticles in Chan-Lam and Suzuki cross-coupling reactions
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A series of highly efficient amine functionalized SiO2-TiO2 supported bimetallic PdCu catalysts with varied metal composition have been synthesized. Ethane-1,2-diamine, butane-1,4-diamine and hexane-1,6-diamine were employed as interparticle linkers for amine functionalization of a SiO2-TiO2 support material so as to study the effect of pendant chain length on stabilization and immobilization of bimetallic nanoparticles. The shortest carbon chain length on the support provided the best results, which may be due to the trapping of metal nanoparticles more efficiently by the basic nitrogen sites. The catalytic activities of these materials were evaluated for C-N and C-C coupling reactions. The most active catalyst, Pd1Cu1@12DA-STS, was characterized by various techniques including SEM, HR-TEM, ICP-AES, XRD, FTIR, EDX, CHN analysis and TGA studies. Moreover, the synthesized catalyst was found to be recyclable for up to five runs without significant loss of activity.
- Jamwal, Babita,Kaur, Manpreet,Sharma, Harsha,Khajuria, Chhavi,Paul, Satya,Clark
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p. 4919 - 4928
(2019/03/26)
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- Catalytic Au(i)/Au(iii) arylation with the hemilabile MeDalphos ligand: Unusual selectivity for electron-rich iodoarenes and efficient application to indoles
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The ability of the hemilabile (P,N) MeDalphos ligand to trigger oxidative addition of iodoarenes to gold has been thoroughly studied. Competition experiments and Hammett correlations substantiate a clear preference of gold for electron-enriched substrates both in stoichiometric oxidative addition reactions and in catalytic C-C cross-coupling with 1,3,5-trimethoxybenzene. This feature markedly contrasts with the higher reactivity of electron-deprived substrates typically encountered with palladium. Based on DFT calculations and detailed analysis of the key transition states (using NBO, CDA and ETS-NOCV methods in particular), the different behavior of the two metals is proposed to result from inverse electron flow between the substrate and metal. Indeed, oxidative addition of iodobenzene is associated with a charge transfer from the substrate to the metal at the transition state for gold, but opposite for palladium. The higher electrophilicity of the gold center favors electron-rich substrates while important back-donation from palladium favors electron-poor substrates. Facile oxidative addition of iodoarenes combined with the propensity of gold(iii) complexes to readily react with electron-rich (hetero)arenes prompted us to apply the (MeDalphos)AuCl complex in the catalytic arylation of indoles, a challenging but very important transformation. The gold complex proved to be very efficient, general and robust. It displays complete regioselectivity for C3 arylation, it tolerates a variety of functional groups at both the iodoarene and indole partners (NO2, CO2Me, Br, OTf, Bpin, OMe?) and it proceeds under mild conditions (75 °C, 2 h).
- Rodriguez, Jessica,Zeineddine, Abdallah,Sosa Carrizo, E. Daiann,Miqueu, Karinne,Saffon-Merceron, Nathalie,Amgoune, Abderrahmane,Bourissou, Didier
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p. 7183 - 7192
(2019/08/07)
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- A micellar catalysis strategy applied to the Pd-catalyzed C-H arylation of indoles in water
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The selective control over multiple competing C-H sites would enable straightforward access to functionalized indoles. In this context, we report here a modular and selective C-H arylation of indoles following the micellar catalysis approach using the third generation "designer" surfactant SPGS-550-M in the presence of 1 mol% of [(cinnamyl)PdCl]2 under mild conditions. Thus, access to high value C-arylated (C-3 and C-2) indoles was achieved fulfilling the "triple bottom line philosophy" of green chemistry. The nature of the phosphine ligand was found to be critical for achieving site-selectivity, DPPF and DPPP being the most effective in promoting the arylation at C3-H and C2-H, respectively. The reaction is scalable and offers high chemo- (C vs. N) and regio-selectivity (C-3 vs. C-2) with a wide range of functional group tolerance. The surfactant aqueous solution can be recycled and reused without compromising on product yields.
- Vaidya, Gargi Nikhil,Fiske, Sneha,Verma, Hansa,Lokhande, Shyam Kumar,Kumar, Dinesh
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supporting information
p. 1448 - 1454
(2019/03/26)
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- Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism
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The direct cyanomethylation of indoles at the 2- or 3-position was achieved via photoredox catalysis. The versatile nitrile synthon is introduced as a radical generated from bromoacetonitrile, a photocatalyst, and blue LED as a light source. The mechanism of the reaction is explored by determination of the Stern-Volmer quenching constants. By combining photophysical data and mass spectrometry to follow the catalyst decomposition, the catalyst ligands were tuned to enable synthetically useful yields of radical coupling products. A range of indole substrates with alkyl, aryl, halogen, ester, and ether functional groups participate in the reaction, affording products in 16-90% yields. The reaction allows the rapid construction of synthetically useful cyanomethylindoles, products that otherwise require several synthetic steps.
- O'Brien, Connor J.,Droege, Daniel G.,Jiu, Alexander Y.,Gandhi, Shivaani S.,Paras, Nick A.,Olson, Steven H.,Conrad, Jay
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p. 8926 - 8935
(2018/07/05)
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- Synthesis of topologically constrained naphthalimide appended palladium(ii)-N-heterocyclic carbene complexes-insights into additive controlled product selectivity
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Topologically constrained naphthalimide appended Pd-NHCs were synthesized and characterized. These structurally related complexes were catalytically compared with previously synthesized Pd-NHCs in the regioselective heteroannulation of o-haloanilines and
- Panyam, Pradeep Kumar Reddy,Sreedharan, Ramdas,Gandhi, Thirumanavelan
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p. 4357 - 4364
(2018/06/22)
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- Synthesis of Bi(hetero)aryls via Sequential Oxidation and Decarboxylation of Benzylamines in a Batch/Fully Automated Continuous Flow Process
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Catalytic dehydrogenative cross-coupling of two C–H bonds represents a green strategy in view of the atom- and step-economy. However, the challenge is to discover a new innovative bond strategy, especially for the direct coupling between Csp2–H
- Mahajan, Bhushan,Aand, Dnyaneshwar,Singh, Ajay K.
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supporting information
p. 2831 - 2835
(2018/06/21)
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- Preparation method of 3-substituted oxidized indole and derivative
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The invention belongs to the technical field of organic chemistry and pharmaceutical chemistry and particularly relates to a method of preparing 3-substituted oxidized indole and a derivative. In themethod, with a 3-substituted indole derivative as a raw material and one or more of a tetrabutyl ammonium halide compound/sodium chloride/sodium iodide/potassium iodide as additives, and one or more of dichloromethane/1,2-dichloroethane/tetrahydrofurane/methylbenzene/1,4-dioxane/ethyl acetate/methanol are added as solvents; then one or more of [bis(trifluoroacetoxyl)iodine]benzene/iodosobenzene diacetate are added as oxidants in order to carry out a reaction with reaction temperature being controlled, thus producing the 3-substituted oxidized indole derivative. The method has gentle reaction conditions, simple operations, short reaction time and high yield, and is free of a metal catalyst and is environment-friendly.
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Paragraph 0050; 0052; 0141
(2018/06/26)
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- Investigation of active sites for C–H functionalization on carbon-based catalyst: Effect of nitrogen-containing functional groups and radicals
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Transition metal catalyzed carbon-carbon bond formation reactions have become important transformations in organic synthesis. In this study, we have explored a general strategy of transition metal free carbocatalytic carbon–hydrogen (C–H) functionalization. A carbon-based catalyst bearing nitrogen functional groups can facilitate the C–H functionalization of unactivated arenes to obtain biaryl products. We propose the active sites on the catalyst by analyzing its chemical composition before and after reaction, in-situ FT-IR, in-situ electron spin resonance (ESR), and density function theory calculation. As a result, stable NH groups and radicals were found to be effective for the reaction, providing high recyclability of the catalyst. The present methodology offers a diverse substrate scope without any dry or inert conditions, thus opening the door for an alternative to the conventional metal-based coupling reactions.
- Sohail Ahmad, Muhammad,Suzuki, Hideyuki,Wang, Chen,Zhao, Min,Nishina, Yuta
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p. 344 - 350
(2018/07/31)
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- Aerobic, Metal-Free, and Catalytic Dehydrogenative Coupling of Heterocycles: En Route to Hedgehog Signaling Pathway Inhibitors
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The nitrosonium ion-catalyzed dehydrogenative coupling of heteroarenes under mild reaction conditions is reported. The developed method utilizes ambient molecular oxygen as a terminal oxidant, and only water is produced as byproduct. Dehydrogenative coupl
- Bering, Luis,Paulussen, Felix M.,Antonchick, Andrey P.
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supporting information
p. 1978 - 1981
(2018/04/16)
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- Synthesis of Indoles from 2-Vinylanilines with PIFA or TFA and Quinones
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The cyclizations involved in the synthesis of different indoles from 2-vinylanilines with PIFA {[bis(trifluoroacetoxy)iodo]benzene} and quinones have been developed under mild conditions. Various substituents on 2-vinylanilines induced good compatibility and gave the desired products in moderate to good yields.
- Wu, Mingzhong,Yan, Rulong
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p. 729 - 733
(2017/03/21)
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- A Copper-Catalyzed Aerobic [1,3]-Nitrogen Shift through Nitrogen-Radical 4-exo-trig Cyclization
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A novel radical [1,3]-nitrogen shift catalyzed by copper diacetate under an oxygen atmosphere (1 atm) has been developed for the construction of a diverse range of indole derivatives from α,α-disubstituted benzylamine. In this reaction, oxygen was used as a clean terminal oxidant, and water was produced as the only by-product. Five inert bonds were cleaved, and two C?N bonds and one C?C double bond were constructed in one pot during this transformation. This unique method demonstrated broad application protential for the late-stage modification of biologically active natural products and drugs. Mechanistic investigations indicate that a unique 4-exo-trig cyclization of an aminyl radical onto a phenyl ring is involved in the catalytic cycle.
- Li, Yan,Wang, Rui,Wang, Tao,Cheng, Xiu-Fen,Zhou, Xin,Fei, Fan,Wang, Xi-Sheng
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supporting information
p. 15436 - 15440
(2017/11/01)
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- Ruthenium-Catalyzed Cycloisomerization of 2-Alkynylanilides: Synthesis of 3-Substituted Indoles by 1,2-Carbon Migration
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We developed ruthenium-catalyzed cycloisomerization of alkynylanilides that gave 3-substituted indoles in high yields. The reaction proceeded via the disubstituted vinylidene ruthenium complex that was formed by the 1,2-carbon migration.
- Watanabe, Takuma,Mutoh, Yuichiro,Saito, Shinichi
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supporting information
p. 7749 - 7752
(2017/06/21)
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- Palladium-Catalyzed Regioselective Synthesis of 3-Arylindoles from N-Ts-Anilines and Styrenes
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A Pd-catalyzed intermolecular oxidative annulation between N-Ts-anilines and styrenes was developed. This method offers a straightforward and robust approach to a wide range of 3-arylindoles using readily available starting materials with good functional-group tolerance and high regioselectivity and efficiency. Further elaboration of the products obtained from this process provided access to highly functionalized and structurally diverse indoles, for example, 3-(indol-3-yl)carbazoles, 1,9-dihydropyrrolo-[2,3-b]carbazoles, and 3′-aryl-3,5′-biindoles.
- Youn, So Won,Ko, Tae Yun,Jang, Young Ho
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supporting information
p. 6636 - 6640
(2017/05/29)
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- Transition-Metal-Free C3 Arylation of Indoles with Aryl Halides
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We report an unprecedented transition metal-free coupling of indoles with aryl halides. The reaction is promoted by KOtBu and is regioselective for C3 over N. The use of degassed solvents devoid of oxygen is necessary for the success of the transformation. Preliminary studies implicate a hybrid mechanism that involves both aryne intermediates and non-propagative radical processes. Electron transfer is also a distinct possibility. These conclusions were substantiated by EPR data, isotopic labeling studies, and the use of radical scavengers and electron transfer inhibitors.
- Chen, Ji,Wu, Jimmy
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supporting information
p. 3951 - 3955
(2017/03/27)
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- Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides
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Metal carbenes can undergo a myriad of synthetic transformations. Sulfur ylides are potential safe precursors of metal carbenes. Herein, we report cascade reactions that involve carbenoids derived from sulfoxonium ylides for the efficient and regioselective synthesis of indoles and pyrroles. The tandem action of iridium and Br?nsted acid catalysts enables rapid assembly of the heterocycles from unmodified anilines or readily accessible enamines under microwave irradiation. The key mechanistic steps are the catalytic transformation of the sulfoxonium ylide into an iridium–carbene complex, followed by N?H or C?H functionalization of an aniline or enamine, respectively, and a final acid-catalyzed cyclization. The present method was successfully applied to the synthesis of the densely functionalized pyrrole subunit of atorvastatin.
- Vaitla, Janakiram,Bayer, Annette,Hopmann, Kathrin H.
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p. 4277 - 4281
(2017/04/03)
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- Pyridylmethylamine–Palladium Catalytic Systems: A Selective Alternative in the C?H Arylation of Indole
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A highly efficient pyridylmethylamine-Pd alternative catalytic system for the C?H arylation of indole was explored. Variously substituted aryl groups were regio- and chemoselectively installed at the indole nucleus by using barium hydroxide as the base. The method was found to be efficient even in the presence of hindered coupling partners and Pd-reactive bonds.
- Perato, Serge,Large, Benjamin,Lu, Qiao,Gaucher, Anne,Prim, Damien
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p. 389 - 392
(2017/02/15)
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- Csp2-Csp2 and Csp2-N Bond Formation in a One-Pot Reaction between N-Tosylhydrazones and Bromonitrobenzenes: An Unexpected Cyclization to Substituted Indole Derivatives
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A novel, sequential, palladium-catalyzed, cross-coupling reaction using N-tosylhydrazone and bromonitrobenzene derivatives followed by reductive cyclization has been developed. This transformation providing an efficient route to unexpected N-arylindole derivatives involves, in a one-pot reaction, the formation of one Csp2-Csp2 bond and two Csp2-N bonds together with the cleavage of one Csp2-heteroatom bond. Evaluation of the biological activity led to the identification of compound 5a, which displays potent activity at nanomolar concentrations against human colon carcinoma cell line.
- Bzeih, Tourin,Lamaa, Diana,Frison, Gilles,Hachem, Ali,Jaber, Nada,Bignon, Jerome,Retailleau, Pascal,Alami, Mouad,Hamze, Abdallah
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supporting information
p. 6700 - 6703
(2017/12/26)
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- Palladium/copper-catalyzed arylation of alkenes with N′-acyl arylhydrazines
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A novel ligand-free palladium/copper-catalyzed Heck-type coupling reaction of alkenes and N′-acyl arylhydrazines has been developed by using air as the terminal oxidant. This protocol features wide functional group tolerance and produces highly chemoselective and regioselective products with good to excellent yields.
- Zhang, Ji-Quan,Cao, Jun,Li, Wei,Li, Shu-Min,Li, Yong-Kang,Wang, Jian-Ta,Tang, Lei
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supporting information
p. 437 - 441
(2017/02/05)
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- Copper-mediated intramolecular aza-Wacker-type cyclization of 2-alkenylanilines toward 3-aryl indoles
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A copper-mediated intramolecular aza-Wacker-type cyclization was developed for the direct and efficient synthesis of 3-aryl indoles using 2-alkenylanilines in moderate to good yields with good functional group compatibility. This strategy shows the high efficiency, operational simplicity as well as broad substrate scope.
- Yang, Rui,Yu, Jin-Tao,Sun, Song,Zheng, Qingheng,Cheng, Jiang
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p. 445 - 448
(2017/01/11)
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- Iron-Catalyzed Reductive Cyclization of o-Nitrostyrenes Using Phenylsilane as the Terminal Reductant
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Using microscale high-throughput experimentation, an efficient, earth-abundant iron phenanthroline complex was discovered to catalyze the reductive cyclization of ortho-nitrostyrenes into indoles via nitrosoarene reactive intermediates. This method requires only 1 mol % of Fe(OAc)2 and 1 mol % of 4,7-(MeO)2phen and uses phenylsilane as a convenient terminal reductant. The scope and limitations of the method were illustrated with 21 examples, and an investigation into the kinetics of the reaction revealed first-order behavior in catalyst and silane and zero-order behavior with respect to nitrostyrene.
- Shevlin, Michael,Guan, Xinyu,Driver, Tom G.
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p. 5518 - 5522
(2017/08/17)
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- Palladium-catalyzed direct C3-selective arylation of n-unsubstituted indoles with aryl chlorides and triflates
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The direct C3-arylation of N-unsubstituted indoles with aryl chlorides and triflates has been realized using a palladium-dihydroxyterphenylphosphine (DHTP) catalyst. The site selectivity is different from that obtained with other structurally related ligands. This unique feature of the DHTP ligand is attributed to complex formation between the lithium salts of the ligand and the indole. The method was applied to the late-stage derivatization of pharmaceuticals having a chloro group.
- Yamaguchi, Miyuki,Suzuki, Kohei,Sato, Yusuke,Manabe, Kei
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supporting information
p. 5388 - 5391
(2017/11/07)
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