- Switchable Regioselective 6-endo or 5-exo Radical Cyclization via Photoredox Catalysis
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Controlling the regioselectivity of radical cyclizations to favor the 6-endo mode over its kinetically preferred 5-exo counterpart is difficult without introducing substrate prefunctionalization. To address this challenge, we have developed a simple method for reagent controlled regioselective radical cyclization of halogenated N-heterocycles onto pendant olefins. Radical generation occurs under mild photoredox conditions with control of the regioselectivity governed by the rate of hydrogen atom transfer (HAT). Utilizing a polarity-matched thiol-based HAT agent promotes the highly selective formation of the 5-exo cyclization product. Conversely, limiting the solubility of the HAT reagent Hantzsch ester (HEH) leads to selective formation of the thermodynamically favored 6-endo product. This occurs through an initial 5-exo cyclization, with the resulting alkyl radical intermediate undergoing neophyl rearrangement to form the 6-endo product. Development of this switchable catalysis strategy allows for two modes of divergent reactivity to form either the 6-endo or 5-exo product, generating fused N-heteroaromatic/saturated ring systems.
- Blakey, Simon B.,Hendy, Cecilia M.,Jui, Nathan T.,Maust, Mark C.
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p. 3776 - 3781
(2022/03/08)
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- Electrochemical Synthesis of Benzo[ d]imidazole via Intramolecular C(sp3)-H Amination
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An electrochemical dehydrogenative amination for the synthesis of benzimidazoles was developed. This electrosynthesis method could address the limitations of the C(sp3)-H intramolecular amination synthesis reaction and provide novel access to obtain 1,2-disubstituted benzimidazoles without transition metals and oxidants. Under undivided electrolytic conditions, various benzimidazole derivatives could be synthesized, exhibiting functional group tolerance.
- Li, An,Li, Caohui,Li, Lijun,Liu, Yu,Tang, Kewen,Yang, Tao,Yang, Zan,Zhou, Congshan
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- Study of the Effect of Substituents of ortho-Phenylenediamines in the Opening of Lactones and Lactams for Access to Benzimidazol-2-yl Alkanols and Benzimidazol-2-yl Alkylamines
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Benzimidazoles represent common chemical moieties in bioactive compounds. The synthesis of this heterocycle often involves a condensation of an ortho-phenylenediamine with a carboxylic acid derivative. The observed dialkylation of the starting ortho-phenylenediamine is avoided by opening of lactones or lactams. This strategy can directly yield 1 H-benzimidazoles substituted at the 2-position by a functionalized chain. We present herein a study of the effect of different electron-withdrawing or electron-donating groups at the 4-position of ortho-phenylenediamines on the opening of lactones or lactams to synthesize benzimidazol-2-yl alkanols and benzimidazol-2-yl alkylamines.
- Arimondo, Paola B.,Balleé, Alexia,Beaurain, Florian,Castillo-Aguilera, Omar,Depreux, Patrick,Goossens, Laurence
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p. 1216 - 1220
(2020/07/30)
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- Electroreductive heterocyclization of ortho-piperidino substituted nitro(het)arenes
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Electrochemical reduction of ortho-piperidino substituted nitro(het)arenes in an undivided cell on a lead cathode in 8% HCl gave either 1,2,3,4-tetrahydropyrido[1,2-a]-benzimidazoles or 6,7,8,9-tetrahydropyrido[3′,2′:4,5]- imidazo[1,2-a]pyridines. The red
- Begunov, Roman S.,Minyaev, Mikhail E.,Sakulina, Valeria O.,Saverina, Evgeniya A.,Sokolov, Alexandr A.,Syroeshkin, Mikhail A.
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p. 633 - 635
(2020/10/09)
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- Synthesis of rutaecarpine alkaloids: Via an electrochemical cross dehydrogenation coupling reaction
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Substrates are directly oxidized at the anode without using any metal catalyst and oxidant to obtain a series of nitrogen heterocyclic compounds, including benzimidazoles and quinolinones. These compounds are highly tolerant to various functional groups and heterocycle-containing substrates. In addition, natural alkaloids, such as rutaecarpine and deoxyvasicinone, can be synthesized by this method.
- Li, Qian-Yu,Cheng, Shi-Yan,Tang, Hai-Tao,Pan, Ying-Ming
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supporting information
p. 5517 - 5520
(2019/10/28)
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- Metal-Free Sequential C(sp2)-H/OH and C(sp3)-H Aminations of Nitrosoarenes and N-Heterocycles to Ring-Fused Imidazoles
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Hydrogen bond assisted ortho-selective C(sp2)-H amination of nitrosoarenes and subsequent α-C(sp3)-H functionalization of aliphatic amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compounds with N-heterocycles provides a facile excess to a wide range of biologically relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, respectively. Nucleophilic aromatic hydrogen substitution (SNArH) was found to be preferred over classical SNAr reaction during the C(sp2)-H amination of halogenated nitrosoarenes.
- Purkait, Anisha,Roy, Subhra Kanti,Srivastava, Hemant Kumar,Jana, Chandan K.
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p. 2540 - 2543
(2017/05/24)
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- Copper-Catalyzed Double C-N Bond Formation for the Synthesis of Diverse Benzimidazoles from N -Alkyl-2-iodoaniline and Sodium Azide
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An efficient approach to the synthesis of benzimidazole derivatives has been achieved by copper-catalyzed double C-N bonds formation of N-alkyl-2-iodoaniline and sodium azide. The reaction was supposed to proceed through copper-catalyzed tandem reaction of SNAr reaction, aerobic oxidation of C(sp3)-H bond and intramolecular C-N bond formation sequence. Structurally diverse 2-aryl, alkenyl and alkyl benzoimidazole derivatives were assembled by this methodology.
- Chen, Zhengkai,Li, Hongli,Cao, Gangjian,Xu, Jianfeng,Miao, Maozhong,Ren, Hongjun
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supporting information
p. 504 - 508
(2017/02/24)
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- Formic acid as a sustainable and complementary reductant: An approach to fused benzimidazoles by molecular iodine-catalyzed reductive redox cyclization of: O -nitro- t -anilines
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Molecular iodine was found to be an excellent catalyst for reductive redox cyclization of o-nitro-t-anilines 1 into fused tricyclic or 1,2-disubtituted benzimidazoles 2. A range of functional groups such as halides (F, Cl, Br), methoxy, ester, trifluoromethyl, cyano, pyridine and even nitro groups were tolerated using formic acid as a clean, safe, user-friendly and complementary reductant. When iodine was used in a stoichiometric amount (50 mol%), the methodology allowed the direct synthesis of benzimidazole hydroiodides 2·HI in high yields by simple precipitation from the reaction mixture.
- Nguyen,Ermolenko,Al-Mourabit
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supporting information
p. 2966 - 2970
(2016/06/09)
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- Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling
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Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.
- Sun, Xiang,Lv, Xiao-Hui,Ye, Lin-Miao,Hu, Yu,Chen, Yan-Yan,Zhang, Xue-Jing,Yan, Ming
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p. 7381 - 7383
(2015/07/15)
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- Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling
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Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.
- Sun, Xiang,Lv, Xiao-Hui,Ye, Lin-Miao,Hu, Yu,Chen, Yan-Yan,Zhang, Xue-Jing,Yan, Ming
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p. 7381 - 7383
(2015/11/27)
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- Barton esters for initiator-free radical cyclisation with heteroaromatic substitution
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S-(1-Oxido-2-pyridinyl)-1,1,3,3-tetramethylthiouronium hexafluorophosphate (HOTT) facilitates the first examples of efficient radical cyclisation with (hetero)aromatic substitution via Barton ester intermediates. Cyclopropyl and alkyl radicals allow acces
- Coyle, Robert,Fahey, Karen,Aldabbagh, Fawaz
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p. 1672 - 1682
(2013/03/28)
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- Metal-free construction of tricyclic or tetracyclic compounds - Acid-promoted synthesis of benzo[4,5]imidazo[2,1-a]isoindole and 1,2-dialkyl-2,3-dihydrobenzimidazoles
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An environmental friendly, efficient, and easy to operate strategy for synthesizing of benzo[4,5]imidazo[2,1-a]isoindole and 1,2-dialkyl-2,3- dihydrobenzimidazoles via acid-promoted coupling of dialdehyde and o-diaminobenzene under metal-free conditions is described. A series of products were generated in good yields under mild conditions.
- Chen, Jinying,Qu, Jinpeng,Zhang, Yuanqing,Chen, Yongxin,Liu, Na,Chen, Baohua
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supporting information
p. 316 - 319
(2013/01/15)
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- Functionalized orthoesters as powerful building blocks for the efficient preparation of heteroaromatic bicycles
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By combining substituted anilines with functionalized orthoesters, an efficient and connective methodology for the preparation of benzoxazole, benzothiazole, and benzimidazole derivatives has been established. The versatility of this approach enables the development of new libraries of heterocycles containing multifunctional sites.
- Bastug, Gulluzar,Eviolitte, Christophe,Markó, István E.
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supporting information; experimental part
p. 3502 - 3505
(2012/08/08)
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- Synthesis of benzimidazoles by PIDA-promoted direct C(sp2)-H imidation of N-arylamidines
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A metal-free synthesis of diversified benzimidazoles from N-arylamidines through a phenyliodine(III) diacetate (PIDA) promoted intramolecular direct C(sp2)-H imidation has been developed. The reaction proceeds smoothly at 0 °C or ambient temperature to provide the desired products in good to excellent yields. The synthesis of 2-alkyl- or 2-alkyl-fused benzimidazoles, which are generally inaccessible by similar Pd- or Cu-catalyzed approaches, can also be achieved. Copyright
- Huang, Jinbo,He, Yimiao,Wang, Yong,Zhu, Qiang
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supporting information
p. 13964 - 13967
(2013/01/15)
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- Synthesis of annulated benzimidazoles via amidine cyclization
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Structurally diverse annulated benzimidazoles were synthesized via two copper(I)-catalyzed cyclocondensation reactions. In the first case the title compounds were prepared from lactams and o-bromoaniline. An alternative route consisted of an intramolecular cyclization of o-bromoarylamidines.
- Liubchak, Kostiantyn,Nazarenko, Kostiantyn,Tolmachev, Andrey
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experimental part
p. 2993 - 3000
(2012/05/31)
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- A direct, regioselective palladium-catalyzed synthesis of N-substituted benzimidazoles and imidazopyridines
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Unsymmetric, N-substituted benzimidazoles and imidazopyridines can be prepared directly from 2-halonitroarenes and amides through Pd(TFA) 2/(R)-BINAP-catalyzed cross-coupling and subsequent reductive aminocyclization. This sequence can be conducted by a one-pot procedure. The method is versatile and allows the straightforward, regioselective preparation of these important nitrogen heterocycles. Unsymmetrical, N-substituted benzimidazoles can be prepared directly from 2-halonitroarenes and amides through Pd(TFA)2/(R)-BINAP-catalyzed cross-coupling and subsequent reductive aminocyclization.This sequence can be conducted by a one-pot procedure. The method is versatile and allows the straightforward, regioselective preparation of these important nitrogen heterocycles. Copyright
- Alonso, Jorge,Halland, Nis,Nazare, Marc,R'Kyek, Omar,Urmann, Matthias,Lindenschmidt, Andreas
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supporting information; experimental part
p. 234 - 237
(2011/03/20)
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- CuI-catalyzed amination of arylhalides with guanidines or amidines: A facile synthesis of 1-H-2-substituted benzimidazoles
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(Figure Presented) CuI/L5 (N,N′-dimethylethylenediamine) proves to be an efficient catalyst system for the amination of arylhalides with guanidines. The same catalyst system is then successfully applied to the one-step synthesis of 1-H-2-aminobenzimidazol
- Deng, Xiaohu,McAllister, Heather,Mani, Neelakandha S.
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supporting information; experimental part
p. 5742 - 5745
(2009/12/06)
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- A REGIOSELECTIVE METAL CATALYZED SYNTHESIS OF ANNELATED BENZIMIDAZOLES AND AZABENZIMIDAZOLES
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A regioselective metal catalyzed synthesis of benzimidazoles and azabenzimidazoles The present invention relates to a process for the regioselective synthesis of compounds of the formula (I), wherein R1; R2; R3; R4; J1; J2; J3; J4 and G have the meanings indicated in the claims. The present invention provides a direct metal, e.g. palladium or copper, catalyzed, regioselective process to a wide variety of unsymmetrical, multifunctional N- substituted benzimidazoles or azabenzimidazoles of formula (I) starting from 2-halo- nitroarenes and N-substituted amides useful for the production of pharmaceuticals, diagnostic agents, liquid crystals, polymers, herbicides, fungicidals, nematicidals, parasiticides, insecticides, acaricides and arthropodicides.
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Page/Page column 30-31
(2009/03/07)
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- Aromatic homolytic substitution using solid phase synthesis
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Solid phase synthesis has been used to carry out intramolecular aromatic homolytic substitution with benzoimidazole precursors. The protocol attaches the radical precursors to the resins via the radical leaving groups (in the aromatic homolytic substitution). When the radical reactions are complete, the leaving group, unaltered starting material and reduced uncylised products remain attached to the resin, which facilitates easy separation of the cyclised products. Novel use of focussed microwave irradiation in solid phase radical reactions drastically shortens the reactions times. Tributylgermanium hydride has been used to replace the toxic and troublesome tributyltin hydride in the radical reactions.
- Allin, Steven M.,Bowman, W. Russell,Karim, Rehana,Rahman, Shahzad S.
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p. 4306 - 4316
(2007/10/03)
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- Microwave-assisted C-H bond activation: A rapid entry into functionalized heterocycles
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(Matrix presented) Microwave irradiation strongly accelerates the rhodium-catalyzed intramolecular coupling of a benzimidazole C-H bond to pendant alkenes. The cyclic products were formed in moderate to excellent yields with reaction times less than 20 min. Additionally, the use of microwave irradiation allowed the reactions to be performed without any solvent purification and with minimal precautions to exclude air.
- Tan, Kian L.,Vasudevan, Anil,Bergman, Robert G.,Ellman, Jonathan A.,Souers, Andrew J.
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p. 2131 - 2134
(2007/10/03)
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- Synthesis of annelated imidazoles and benzimidazoles
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A variety of fused ring imidazole or benzimidazole derivatives were prepared through two successive condensations of a dihalide with 4,5- diphenylimidazole or benzimidazole. The 2-methyl substituted derivatives of 4,5-diphenylimidazole or benzimidazole were also used. The size of the annelated ring, which is dependent on the dihalide used, can be varied from five to seven atoms. Initially, N-alkylhalo derivatives were prepared by condensation of the heterocyclic starting materials with a dihalide. Ring closure was then effected through intramolecular condensation of a carbanion derived from the 2-position or the 2-methyl group of the parent heterocyclic ring with the N-alkylhalo moiety.
- McClure, James R.,Custer, John H.,Schwarz, H. Dean,Lill, Deborah A.
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p. 710 - 712
(2007/10/03)
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- Radical cyclisation onto imidazoles and benzimidazoles
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New synthetic methodology has been developed for the synthesis of [1,2- a]fused imidazoles and benzimidazoles using intramolecular homolytic aromatic substitution. In the intramolecular substitution, N-(ω-alkyl) radicals are generated using Bu3SnH from N-(ω-phenylselanyl)alkyl side chains. Phenylselanyl groups are used as radical leaving groups to avoid problems in the N-alkylation of imidazoles and benzimidazoles. Arylsulfones for imidazoles, and phenylsulfides for benzimidazoles, are used at the leaving groups in the homolytic substitutions.
- Aldabbagh, Fawaz,Bowman, W. Russell
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p. 4109 - 4122
(2007/10/03)
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- Radical cyclisation onto imidazoles and benzimidazoles
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A new protocol for the synthesis of [1,2-a]-fused benzimidazoles and imidazoles has been developed using intramolecular homolytic aromatic substitution via ω-alkyl radicals generated from 1-(ω-benzeneselenylakyl)-2(benzenesulfenyl)- benzimidazoles and -2-(p-toluenesulfonyl)imidazoles.
- Aldabbagh, Fawaz,Bowman, W. Russell
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p. 3793 - 3794
(2007/10/03)
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- Synthesis of a conformationally constrained analogue of BW A78U, an anticonvulsant adenine derivative
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The synthesis of a conformationally constrained analogue of the anticonvulsant BW A78U, a 9-benzyl-adenine derivative, has been devised, using silicon tetrachloride in a new cyclodehydration.
- Desaubry, Laurent,Wermuth, Camille Georges,Bourguignon, Jean-Jacques
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p. 4249 - 4252
(2007/10/02)
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- Synthesis of Benzimidazoles Containing a Fused Alicyclic Ring By Rhodium - Catalysed Hydroformylation of N-Alkenyl-1,2-diaminobenzenes
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Rhodium-catalysed reactions of N-alkenyl-1,2-diaminobenzenes (3) with hydrogen and carbon monoxide give benzimidazoles containing a fused alicyclic ring ((8) and (9)) in excellent yields.In some cases intermediate bicyclic compounds can be isolated and the 1H and 13C n.m.r. spectra of one of these, the 3,4,5,6-tetrahydro-4-methyl-3H-1,6-benzodiazocine (6), shows evidence for unusual atropisomerism.
- Anastasiou, Despina,Campi, Eva M.,Chaouk, Hassan,Jackson, W. Roy
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p. 7467 - 7478
(2007/10/02)
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- A metal catalysed route to benzimidazoles containing a fused alicyclic ring
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Rhodium catalysed reactions of N-alkenyl-1,2-diaminobenzenes (1) with hydrogen and carbon monoxide give benzimidazoles containing a fused alicyclic ring (6,7) in excellent yields.
- Anastasiou,Chaouk,Jackson
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p. 2499 - 2500
(2007/10/02)
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- PREPARATION OF SUBSTITUTED, ANNULATED BENZIMIDAZOLES VIA BENZYNE MEDIATED CYCLIZATION
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The synthesis of 1,2-annulated benzimidazoles via an internal benzyne cyclization is described.
- Caroon, Joan M.,Fisher, Lawrence E.
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p. 459 - 467
(2007/10/02)
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