Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• of the corresponding imidoyl chlorides 10 with PCl5 in POCl3, followed by the additional reaction with trifluoromethanesulfonamide (1) and protonation by sulfuric acid (Scheme 1) [10]. In recent years, we have reported high yielding catalyst-free N-arylation by SNAr reaction of mono- or

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• diaryliodonium salts can generate benzynes under severe basic conditions, the resulted benzynes were allowed to undergo cycloaddition reaction with furan or N-arylation of secondary amides and amines. Due to the easy accessibility of the diaryliodonium salts, this kind of benzyne precursor is attracting

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• N-arylation of NH groups under metal-free conditions [35][36][37][38][39]. For example, treatment of arenecarboxylic acids and alkanecarboxylic acids with diaryliodonium salts and t-BuOK under toluene refluxing conditions provides the corresponding aryl carboxylates in good yields [40][41]. However

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• Determining the accurate chemical structures of synthesized compounds is essential for biomedical studies and computer-assisted drug design. The unequivocal determination of N-adamantylation or N-arylation site(s) in nitrogen-rich heterocycles, characterized by a low density of hydrogen atoms, using NMR

• product structure were also found for N-arylation or N-alkylation with tert-butyl fragments in the series of 1,2,3-triazole [15][16], tetrazole [17][18][19][20], and purine [21] derivatives. Meanwhile, knowledge of the accurate chemical structures of N-substituted heterocycles is essential for biomedical

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• ], Ullmann coupling [13][14], Buchwald–Hartwig amination [15] or N-alkylation of carbazole in the presence of alkali metal carbonates under MW irradiation [16]. In our case, the N-arylation was realized under phase transfer conditions using triethylbenzylammonium chloride (TEBA) as a catalyst [17][18

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• : cyclization; indolo[3,2-a]carbazole; N-arylation; oxidative biaryl coupling; palladium catalysis; Introduction Many biologically active carbazole derivatives are of interest as drug-like templates. The indolo[3,2-a]carbazole skeleton, one of the isomeric indolocarbazoles, was firstly identified from nature

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• coupling reactions has not attracted the attention from the organic chemistry community. This may have been due to the fact that these reactions do not allow for the direct creation of new stereochemical centers. Only a few examples were reported for asymmetric N-arylation reactions using a Pd catalytic

• system through an “indirect” way, either by asymmetric desymmetrization or kinetic resolution [40][41][42][43][44]. In most cases, the enantioselectivities were not satisfactory. Recently, a copper catalytic system became another option toward asymmetric N-arylation reactions in term of improving

• ] (Scheme 19). This method was further applied to a double N-arylation reaction for the enantioselective formation of spirobilactams by Cai et al. [49]. Through the combination of the copper-catalyzed double N-arylation and a simple in situ solid–solution phase separation, the spirobilatams were formed in

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• Science and Technology, Qingdao, 266042, China 10.3762/bjoc.11.258 Abstract A series of functionalized benzimidazo[1,2-c]quinazoline derivatives was obtained in excellent yields under mild conditions through a CuI-catalyzed Ullmann N-arylation starting from easily available starting materials. Keywords

• : benzimidazo[1,2-c]quinazoline; (bromophenyl)iodonium salt; copper catalyst; o-cyanoaniline; quinazolin-4(3H)-imine; Ullmann N-arylation; Introduction Nitrogen-containing heterocycles are ubiquitous backbones in natural products, medicine and organic materials. In addition, they are also important ligands for

• are not readily available and need harsh conditions. Herein we report a CuI-catalyzed concise and efficient method for the synthesis of benzimidazo[1,2-c]quinazoline derivatives through the intramolecular N-arylation reaction of bromo-substituted quinazolin-4(3H)-imines that are easily prepared from o

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• obtained together with recovered starting material. In order to test the functionalization of the above synthesized aryl iodides through a subsequent transition-metal-catalyzed coupling reaction we subjected three of them to a copper-catalyzed N-arylation reaction. Thus, the iodides 3b, 3d and 4d were

• compounds 3d and 4d. Procedure 7 for the N-arylation of imidazole [47]. A mixture of the prepared iodide (1.0 mmol), Cu2O (0.10 g, 0.10 mmol), Cs2CO3 (0.65 g, 2.0 mmol), imidazole (0.14 g, 2.0 mmol) and DMSO (0.5 mL) was stirred for 24 h at 110 °C under argon. After cooling to room temperature, the mixture

• and 2d followed by iodolysis. Deproto-metallation of 1e and 2e followed by iodolysis. N-arylation of the iodides 3b, 3d and 4d. Synthesis of the azole substrates 1a,b, 1d,e and 2a–e. Supporting Information Supporting Information File 127: Experimental description of the synthesized compounds, 1H and

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• %, Scheme 12). In another occasion, Rajakumar and co-workers [102] have synthesized a series of stilbenophanes (e.g., 81) involving N-arylated carbazole moieties possessing small and large cavities. The precursor 80 required for the McMurry reaction was synthesized by the N-arylation of carbazole with the

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• to the N-arylation of MPTTFs and BPTTFs using a variety of aryl halides. Keywords: heterocycles; protecting groups; sulfur chemistry; tetrathiafulvalene; Ullman coupling; Introduction Tetrathiafulvalene (TTF) derivatives are of considerable interest in the fields of supramolecular chemistry and

• -cyanoethyl-protected thiols as a means to further functionalise MPTTFs with thioethers and (ii) copper-mediated N-arylation of both MPTTFs and BPTTFs. Results and Discussion An improved large-scale synthesis of N-tosyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (6) The known compound 6 [4][25] is an important

• convenient than the use of CsOH·H2O. N-Arylation of MPTTFs and BPTTFs N-Alkylation of MPTTFs and BPTTFs can be easily achieved using SN2 reactions between a deprotonated pyrrole and a suitably activated aliphatic species [19][28]. N-Arylation of MPTTFs and BPTTFs, which allows an annelated TTF to be

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• direct conjugation with the tetrathiafulvalene chromophore. The crystal packing of the arylated monopyrrolotetrathiafulvalenes is primarily defined by networks of C–H···X weak hydrogen bonds and short S···S contacts involving the tetrathiafulvalene moieties. Keywords: cyclic voltammetry; N-arylation

• in hot triethyl or trimethyl phosphite. Using the second approach [17][18][19], the aryl group is attached to the MPTTF moiety using a direct copper-mediated Ullmann-type N-arylation reaction [20][21]; this method was also used for the preparation of arylated bis-pyrrolotetrathiafulvalenes 2

• moieties directly attached to an aromatic calixarene backbone, we have chosen the copper-catalysed N-arylation reaction as a method for coupling of aromatic and MPTTF moieties with each other and successfully employed it for the preparation of two bis-MPTTF-calixarene conjugates, as well as two model low

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• rather expensive; therefore efforts were made to replace them with cheaper analogues. One successful approach included iron(III) acetylacetonate in acetic acid as catalytic agent (Scheme 16) [37], whereby O-acetyl oximes obtained from 2′-arylacetophenones underwent N–O bond cleavage and intramolecular N

• -arylation. The following conventional cross-coupling or directed C–H arylation resulted in substituted phenanthridines. Homolytic aromatic substitution (HAS) by an aryl radical was used for the construction of biaryl motifs as alternative to transition metal-catalysed C–H bond arylation. That approach was

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• out according to the procedure of Litkey and Patonay [18] affording the racemic 3,4-dihydro-2-phenyl-1,4-benzoxazepine-5-one (rac-9) with high regioselectivity, which was reduced to (rac)-10 with LAH in dry THF. In the following step, the N-arylation of rac-10 was performed through a nucleophilic

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• Ullmann condensation is a powerful method for C–N coupling [24][25][26], especially the N-arylation of nitrogen-containing heterocycles such as indoles [27][28]. Indolo[1,2-a]quinazoline is a kind of tetracyclic compounds containing the indole motif that has been constructed by intramolecular [3 + 2

• domino cyclization. Based on the previous work for the copper-catalyzed synthesis of 2-amino-1H-indole derivatives and copper-catalyzed N-arylation, we herein report a simple and efficient one-pot method to synthesize indolo[1,2-a]quinazolines by a sequential Ullmann-type C–C and C–N coupling. Compared

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• -diarylindoles were successfully reacted with N-Boc-THIQ to furnish 1,2,3-trisubstituted indoles as target compounds. Furthermore, regioselective N-arylation of protected and unprotected 1-(indol-3-yl)-THIQs was successfully conducted using either simple iron or copper salts as catalysts. Keywords: Buchwald

• ][43][44][45]. However, these methods have not been applied on complex molecules leading to sterically crowded compounds. Additionally, N-arylation of indole is well established as well [25][46][47][48][49]. Within this contribution we report a comprehensive investigation of strategies to prepare 1

• will be presented before the final step from these compounds towards target structure 1 will be discussed. Pathways towards intermediates 6–8 Synthesis of intermediate 6 through routes A and B Various reaction conditions have been reported to carry out N-arylation [46][47][48][49] and direct C2

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• cyclized by a copper-catalyzed N-arylation. In the last step, the phosphoramidate is cleaved by an acidic treatment. This sequence illustrates that the AT reaction is compatible with the presence of free carboxylic acid functional group. Aryl dialkyl phosphate, easily prepared starting from phenol in an AT

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• synthesize 5,6-dihydroindolo[1,2-a]quinoxaline derivatives by CuI-catalyzed intramolecular N-arylation under microwave irradiation. This method rapidly afforded the tetracyclic products with good to excellent yields (83–97%) in short reaction times (45–60 min). Keywords: copper; 5,6-dihydroindolo[1,2-a

• ]quinoxaline; intramolecular N-arylation; microwave irradiation; Introduction The indole scaffold is considered as a privileged structure because of its ubiquitous presence in a large number of natural products and pharmaceutical agents [1][2][3][4][5][6]. In particular, indole-fused heterocycles have

• , the copper-catalyzed N-arylation has been extensively utilized for C–N coupling, especially for the arylation of N-containing heterocycles such as indoles, imidazoles, indazoles, pyrroles, pyrazoles and triazoles [25][26][27][28] to construct more fused heterocycles. In recent years, several

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• . Keywords: arylboronic acids; C-nitroazoles; coupling; N-arylation; N-aryl-C-nitroazoles; Introduction The nitroazoles constitute a class of compounds with a broad spectrum of useful properties. They have found applications in agrochemicals as plant-growth regulators [1], herbicides or insecticides [2], in

• substrates such as amines, amides, imides or heterocycles with boronic acids, the method has become a powerful synthetic route for N-arylation. Many investigations concerning the influence of the amount and kind of a catalyst, type of solvent, temperature, the presence of a base, and other reaction

• . The presence of the nitro group (a strong electron-withdrawing substituent) in the azole entails the adjustment of the conditions of N-arylation reaction. Besides a very recently published approach involving N-arylation of nitroazoles with diaryliodonium salts [20], already described methods utilize

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• preparation of N-arylpyrroles is an active field of investigation [5]. Depending on their substituents, N-arylpyrroles could also be electron donor/acceptor molecules with a dual fluorescence ability suggesting attractive optoelectronic applications [6][7]. If the N-arylation of pyrroles is possible by

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• precursor 2c was obtained by an N-arylation, as described in the literature.[21] A modified Buchwald–Hartwig amination reaction using tri-tert-butylphosphane as a ligand at palladium [22] was applied in order to couple 4-methylphenyl bromide and 4-fluorophenyl bromide with Boc-protected aminopiperidines 17

• the solvent in a rotary evaporator, the residue was purified by flash chromatography. For the preparation of catechol-derived acetals 11c and 12c, toluene was used instead of chloroform, and trifluoromethanesulfonic acid instead of p-toluenesulfonic acid. General procedure for the N-arylation of N-Boc

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• Nancy Université, BP 70239, Bd des Aiguillettes, 54506 Vandoeuvre-les-Nancy, France 10.3762/bjoc.8.26 Abstract Unusual 2,7-diazacarbazoles were prepared in one step from readily available tetra-halogenated 4,4’-bipyridines by using a double N-arylation reaction in the presence of the Pd–XPhos catalyst

• -diazacarbazole by using a palladium-catalyzed double N-arylation of 4,4’-dichloro-3,3’-bipyridine, itself obtained after a long reaction sequence [25][26][27]. In another patent, an intramolecular Buchwald–Hartwig amination [28][29] was used to generate a 2,7-diazacarbazole derivative in low yield [30]. Recently

• , we reported a one-step preparation of tetrahalogenated 4,4’-bipyridines 2 starting from 2,5-dihalopyridines 1 [31]. Herein, we report on the synthesis of functionalized 2,7-diazacarbazoles 3 through the double N-arylation of 2. Considering compound 2a, the C–Br over C–Cl regioselectivity was not

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• a Pd-catalyzed cascade sequence, involving an alkenyl amination, a C-arylation and a subsequent intramolecular N-arylation, was developed by Barluenga and coworkers for the preparation of indole derivatives 68 [37]. Here, equimolecular amounts of haloalkene 65, o-dihaloarene 66, and amines are mixed

• basic media. A subsequent Pd-mediated intermolecular alkylation with the dihalogeno substrate followed by an intramolecular N-arylation furnished 2-substituted indoles 68. In this cascade reaction, the palladium catalyst intervenes in three different coupling reactions: Intermolecular N-alkenylation, C

• -arylation and intramolecular N-arylation (Scheme 29). The palladium-mediated amination reaction coupled with a nitrogen–carbon bond-forming reaction was also used for the stereoselective synthesis of N-aryl-2-benzylpyrrolidines 71 starting from linear 4-pentenylamine and its derivatives [38]. In this tandem

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• , transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if

• applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type

• reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N