- Pd-Catalyzed Regioselective Direct Double C–H Arylation of 6,7-Benzindoles
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A palladium-catalyzed protocol for the first direct diarylation of 6,7-benzindoles with aryl iodides at the C4 and C5 positions was developed. The key to this strategy was the employment of pivaloyl as the directing group at the C3 position and the blocking effect at the C6 and C7 positions. The reaction proceeded very well, providing a series of diarylated 6,7-benzindoles without prefunctionalization at the reactive sites. Several examples on the unexpected monoarylation of 6,7-benzindoles at the C5 position were also presented.
- Li, Ping-Gui,Yang, Youqing,Zhu, Shuai,Li, Hong-Xi,Zou, Liang-Hua
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- Diaryliodonium Salt-Based Synthesis of N-Alkoxyindolines and Further Insights into the Ishikawa Indole Synthesis
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A diaryliodonium salt-based strategy enabled the first systematic synthesis of rarely accessible N-alkoxyindolines. Mechanistic analyses suggested that the reaction likely involves reductive elimination of iodobenzene from iodaoxazepine via a four-membered transition state, followed by Meisenheimer rearrangement. Substrates with N-carbamate protection afforded indole in a manner similar to that of the Ishikawa indole synthesis. Preinstallation of a stannyl group as an iodonium salt precursor greatly expanded the substrate scope, and further mechanistic insights are discussed.
- Shibata, Kouhei,Takao, Ken-Ichi,Ogura, Akihiro
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p. 10067 - 10087
(2021/07/26)
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- Straight Access to Indoles from Anilines and Ethylene Glycol by Heterogeneous Acceptorless Dehydrogenative Condensation
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The development of original strategies for the preparation of indole derivatives is a major goal in drug design. Herein, we report the first straight access to indoles from anilines and ethylene glycol by heterogeneous catalysis, based on an acceptorless dehydrogenative condensation, under noninert conditions. In order to achieve high selectivity, a combination of Pt/Al2O3 and ZnO have been found to slowly dehydrogenate ethylene glycol generating, after condensation with the amine and tautomeric equilibrium, the corresponding pyrrole-ring unsubstituted indoles.
- Llabres-Campaner, Pedro Juan,Ballesteros-Garrido, Rafael,Ballesteros, Rafael,Abarca, Belén
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p. 521 - 526
(2018/01/01)
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- Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors
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Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.
- Sellmer, Andreas,Stangl, Hubert,Beyer, Mandy,Grünstein, Elisabeth,Leonhardt, Michel,Pongratz, Herwig,Eichhorn, Emerich,Elz, Sigurd,Striegl, Birgit,Jenei-Lanzl, Zsuzsa,Dove, Stefan,Straub, Rainer H.,Kr?mer, Oliver H.,Mahboobi, Siavosh
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p. 3454 - 3477
(2018/05/01)
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- Phenanthroline- tBuOK Promoted Intramolecular C-H Arylation of Indoles with ArI under Transition-Metal-Free Conditions
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The first example of phenanthroline-tBuOK promoted intramolecular radical C-H arylation of N-(2-iodobenzyl)indoles without involvement of transition metals has been developed. A variety of substituted 6H-isoindolo [2, 1-a] indoles were prepared by a simple and efficient intramolecular cyclization using 1,10-phenanthroline in the presence of potassium tert-butoxide and chlorobenzene. This strategy provides a fast and versatile access to isoindolo[2,1-a]indole derivatives for the synthesis of pharmaceuticals and organic electroluminescent (EL) materials.
- Shan, Xiang-Huan,Yang, Bo,Zheng, Hong-Xing,Qu, Jian-Ping,Kang, Yan-Biao
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supporting information
p. 7898 - 7901
(2019/01/04)
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- Palladium/Phosphorus-Doped Porous Organic Polymer as Recyclable Chemoselective and Efficient Hydrogenation Catalyst under Ambient Conditions
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A new type of phosphorus-doped porous organic polymer (POP) has been readily synthesized through a Heck reaction, which could be used not only as a support but also a ligand for palladium nanoparticles. The dual-functional material supported palladium nanocatalyst was used for the efficient and chemoselective hydrogenation of varieties of nitroarenes and α,β-unsaturated compounds, as well as for the synthesis of indoles from 2-nitrophenylacetonitrile under 1 atm hydrogen in green solvents at room temperature. No obvious aggregation and loss of catalytic activity of the new nanocatalyst were observed after 10 runs in the reaction. (Figure presented.).
- Ding, Zong-Cang,Li, Cun-Yao,Chen, Jun-Jia,Zeng, Jia-Hao,Tang, Hai-Tao,Ding, Yun-Jie,Zhan, Zhuang-Ping
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p. 2280 - 2287
(2017/07/07)
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- Active and Recyclable Catalytic Synthesis of Indoles by Reductive Cyclization of 2-(2-Nitroaryl)acetonitriles in the Presence of Co-Rh Heterobimetallic Nanoparticles with Atmospheric Hydrogen under Mild Conditions
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A cobalt-rhodium heterobimetallic nanoparticle-catalyzed reductive cyclization of 2-(2-nitroaryl)acetonitriles to indoles has been achieved. The tandem reaction proceeds without any additives under the mild conditions (1 atm H2 and 25 °C). This procedure could be scaled up to the gram scale. The catalytic system is significantly stable under these reaction conditions and could be reused more than ten times without loss of catalytic activity.
- Choi, Isaac,Chung, Hyunho,Park, Jang Won,Chung, Young Keun
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p. 5508 - 5511
(2016/11/17)
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- A combined experimental and computational study on the cycloisomerization of 2-ethynylbiaryls catalyzed by dicationic arene ruthenium complexes
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Ruthenium-catalyzed cycloisomerization of 2-ethynylbiaryls was investigated to identify an optimal ruthenium catalyst system. A combination of [η6-(p-cymene)RuCl2(PR3)] and two equivalents of AgPF6 effectively converted 2-ethynylbiphenyls into phenanthrenes in chlorobenzene at 120 °C over 20 h. Moreover, 2-ethynylheterobiaryls were found to be favorable substrates for this ruthenium catalysis, thus achieving the cycloisomerization of previously unused heterocyclic substrates. Moreover, several control experiments and DFT calculations of model complexes were performed to propose a plausible reaction mechanism.
- Yamamoto, Yoshihiko,Matsui, Kazuma,Shibuya, Masatoshi
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supporting information
p. 7245 - 7255
(2015/05/05)
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- N-Heterocyclization of naphthylamines with 1,2- And 1,3-Diols catalyzed by an iridium Chloride/BINAP system
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Benzoquinoline derivatives were successfully synthesized by iridium-catalyzed N-heterocyclization of naphthylamines with diols. For instance, the reaction of 1-naphthylamine with 1,3-propanediol catalyzed by IrCl3 combined with BINAP as a ligand produced 7,8-benzoquinoline in quantitative yield. The VV-heterocyclization reaction was found to be markedly influenced by the ligands employed. Benzoindoles were also synthesized by the same strategy from napthylamines with 1,2-diols. A reaction mechanism for the N-heterocyclization of naphthylamines with 1,3-diols by IrCl3 was proposed.
- Aramoto, Hiroomi,Obora, Yasushi,Ishii, Yasutaka
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scheme or table
p. 628 - 633
(2009/06/28)
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- A peculiar selective rearrangement during the NiS-catalysed dehydrogenation of 4,5-dihydro-1H-benz[g]indole
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The dehydrogenation of 4,5-dihydro-1H-benz[g]indole on NiS/Al2O3 (350 °C) is accompanied by a peculiar rearrangement to give 3H-benz[e]indole (71%).
- Trofimov, Boris A.,Vasil'tsov, Alexander M.,Ushakov, Igor' A.,Ivanov, Andrey V.,Schmidt, Elena Yu.,Mikhaleva, Al'bina I.,Protsuk, Nadezhda I.,Kobychev, Vladimir B.
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p. 296 - 298
(2008/03/12)
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- NOVEL DIPODAZINE COMPOUNDS AND APPLICATIONS
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The invention relates to a novel class of dipodazine derivatives, suitable for use as surface on-growth inhibiting agents.
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Page/Page column 11-12
(2008/06/13)
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- Synthesis of phenanthrenes and polycyclic heteroarenes by transition-metal catalyzed cycloisomerization reactions
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Readily available biphenyl derivatives containing an alkyne unit at one of their ortho-positions are converted into substituted phenanthrenes on exposure to catalytic amounts of either PtCl2, AuCl, AuCl3, GaCl3 or InCl3 in toluene. This 6-endo-dig cyclization likely proceeds through initial π-complexation of the alkyne unit followed by interception of the resulting η2-metal species by the adjacent arene ring. The reaction is inherently modular, allowing for substantial structural variations and for the incorporation of substituents at any site of the phenanthrene product. Moreover, it is readily extended to the heterocyclic series as exemplified by the preparation of benzoindoles, benzocarbazoles, naphthothiophenes, as well as bridgehead nitrogen heterocycles such as pyrrolo[1,2-a]quinolines. Depending on the chosen catalyst, biaryls bearing halo-alkyne units can either be converted into the corresponding 10-halo-phenanthrenes or into the isomeric 9-halo-phenanthrenes; in the latter case, the concomitant 1,2-halide shift is best explained by assuming a metal vinylidene species as the reactive intermediate. The scope of this novel method for the preparation of polycyclic arenes is illustrated by the total synthesis of a series of polyoxygenated phenanthrenes that are close relatives of the anticancer agent combretastatin A-4, as well as by the total synthesis of the aporphine alkaloid O-methyl-dehydroisopiline and its naturally occurring symmetrical dimer.
- Mamane, Victor,Hannen, Peter,Fuerstner, Alois
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p. 4556 - 4575
(2007/10/03)
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- Microwave assisted Leimgruber-Batcho reaction for the preparation of indoles, azaindoles and pyrroylquinolines
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The development of enhanced conditions for Lewis acid catalysed Leimgruber-Batcho indole synthesis using microwave acceleration is described. This approach has permitted the preparation of a variety of heteroaromatic enamine intermediates in good yield and high purities. Subsequent catalytic hydrogenation reactions, under various conditions including the use of a solid-phase encapsulated catalyst, furnish the corresponding indole derivatives in good yields.
- Siu, Jason,Baxendale, Ian R.,Ley, Steven V.
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p. 160 - 167
(2007/10/03)
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- Flexible synthesis of phenanthrenes by a PtCl2-catalyzed cycloisomerization reaction
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Readily available biphenyl derivatives containing an alkyne unit at one of their ortho positions are converted into substituted phenanthrenes upon exposure to catalytic amounts of either PtCl2, AuCl3, GaCl3, or InCl3 in toluene. This 6-endo-dig cyclization likely proceeds through initial π-coordination of the alkyne unit followed by interception of the resulting η2-metal complex by the adjacent arene ring. The reaction is inherently modular, allowing for substantial structural variations and for the incorporation of substituents at any site of the phenanthrene product except C-9. Moreover, the reaction is readily applied to the heterocyclic series as exemplified by the preparation of benzoindoles, naphthothiophenes as well as bridgehead nitrogen hetero- cycles.
- Fuerstner, Alois,Mamane, Victor
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p. 6264 - 6267
(2007/10/03)
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- The synthesis and evaluation of benzannelated-azatoxins: The benzazatoxins
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The synthesis and evaluation of azatoxin congeners possessing annealed aromatic frameworks are described. The compounds were evaluated for their abilities to affect topoisomerase II inhibition through the stabilization of 'cleavable complex' and for the inhibition of tubulin polymerization using purified bovine brain tubulin.
- Miller, Thomas A.,Vachaspati, Prakash R.,Labroli, Marc A.,Thompson, Charles D.,Bulman, Amanda L.,Macdonald, Timothy L.
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p. 1065 - 1070
(2007/10/03)
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- Substituted N-aryl alk-1-enesulfinamides: Preparation, properties and conversion into the corresponding indole compounds [1]
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Reaction of vinylic organometallic derivatives with N-sulfinyl arenamines 2 affords the title sulfinamides 3. On heating their solutions in selected solvents to 80-124 °C, these sulfinamides are converted into the corresponding indoles 6, probably via a [3.3]-sigmatropic rearrangement to intermediates VIII which undergo an intramolecular carbophilic reaction of the nitrogen atom with the neighboring sulfine group, followed by elimination of HSOH. The triethyloxonium tetrafluoroborate- or boron trifluoride etherate catalyzed conversion 3 → 6 can be carried out at a much lower temperature. Elsevier,.
- Baudin, Jean-Bernard,Commenil, Marie-Gabrielle,Julia, Sylvestre A.,Lorne, Robert,Mauclaire, Laurent
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p. 329 - 350
(2007/10/03)
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- Photolysis of 1-Aryl-1,2,3-triazoles; Rearrangement via !H-Azirines
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The preparation and photolysis of a series of 1-(1-naphthyl)-1,2,3-triazoles, (2)-(5), and of 1-(2-methyl-1-naphthyl)-1,2,3-triazoles, (6)-(9), with and without electron-withdrawing groups (CO2R, CONH2, CN, CHO, COPh) in the triazole ring, are described.In the first series, triazoles (3) with two electron-withdrawing groups, and triazoles (4) with one such group at C-4, mostly give good yields of the expected benzindoles (10) and 11 respectively.Triazoles (5) with the electron-withdrawing group at C-5 also give benzindoles but these are now mixtures of the expected (12) and rearranged indoles (11).Photolysis of the 1-phenyltriazoles (21) and (22) follows the same pattern, those with the electron-withdrawing group at C-5 rearranging to give mixtures of indoles (23) and (24).This is explained by a mechanism (Scheme 3) in which the less stable carbene intermediate (13) rearranges to the more stable carbene (15) via the 1H-azirine (14), in competition with its direct cyclisation.This provides the first evidence for antiaromatic 1H-azirines as intermediates in a photochemical reaction.Photolysis of the 2-methylnaphthyl compounds follows a different path: diester (7b) and dinitrile (7d) give high yields of the deeply coloured 9-methyl-1H-benzoquinoline derivatives (25a) and (25b) respectively, the first stable examples of this ring system to be isolated.Photolysis of the nitrile (8c) gives 9b-methyl-9bH-benzindole-3-carbonitrile (28), a rare example of a stable indole with a ring junction substituent. 1,2-Shifts in the carbenes are only observed with the bis(trimethylsilyl)triazoles (2d) and (6f), in keeping with the known rapid migration of trimethylsilyl groups to carbene centres.
- Mitchell, Glynn,Rees, Charles W.
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p. 413 - 422
(2007/10/02)
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- N-ARYL-ETHENESULPHENAMIDES; THERMAL TRANSFORMATION OF TWO N-(1-NAPHTHYL)-ETHENESULPHENAMIDES INTO 1H-BENZINDOLES
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Reaction of vinylmagnesium bromide with morpholine or piperidine-N-sulphenyl chlorides 3a,b affords the N-ethenylthio-morpholine and -piperidine 4a,b.When treated with stoichiometric amounts of an arylamine and methanesulphonic (or trifluoroacetic) acid, the sulphenamides 4 are converted into N-aryl-ethenesulphenamides 6a-e.On heating in toluene, two of these sulphenamides 6d and 6e undergo -sigmatropic rearrangements followed by cyclisation of the intermediate amino-thioaldehydes yielding the corresponding 1H-benzindoles 8a,b.
- Baudin, Jean-Bernard,Julia, A. Sylvestre,Ruel, Odile
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p. 881 - 890
(2007/10/02)
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- CONDENSED HETEROAROMATIC SYSTEMS. X. SYNTHESIS OF BENZINDOLES FROM o-BROMONAPHTHYLAMINES
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benzindole, of which few effective preparative methods are known, was easily synthesized by palladium-catalyzed reaction of ethyl 3-bromo-2-naphthylcarbamate with trimethylsilylacetylene and subsequent cyclization with sodium ethoxide in ethanol.By the same method , benzindole and benzindole were obtained from 2-bromo-1-naphthylcarbamate and 1-bromo-2-naphthylcarbamate, respectively.
- Sakamoto, Takao,Kondo, Yoshinori,Yamanaka, Hiroshi
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p. 1845 - 1847
(2007/10/02)
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