Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• -guided electrophilic substitution (HIGES). Keywords: electrophilic aromatic substitution; hypernucleofugality; hypervalent iodine; iodonio-Claisen; transmetallation; Introduction Hypervalent iodine compounds have been known for over a hundred years, but it was not until their renaissance in the 1990’s

• hypervalent iodine-guided electrophilic substitution (HIGES) reaction were performed by varying the hypervalent iodine starting material, the activator, the solvent, and the temperature at which the activated hypervalent iodine reagent formed (Table 1). Varying the temperature at 25 °C, 0 °C, and −50 °C did

• in an electrophilic substitution on the transmetallated benzyl hypervalent iodine intermediate. If such a stepwise mechanism were to occur then one would expect to see an additional coupling product. Based on the evidence provided by these crossover reactions it rules out such a stepwise reaction

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• suggest that the [4 + 2]-cycloaddition process (2) is thermodynamically favored for nitrosoalkenes bearing electron-donating group R, whereas the presence of an electron withdrawing group at the same position promotes the electrophilic substitution pathway (1). Pinho e Melo and co-workers developed a one

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

• mobility. Carbazole undergoes electrophilic substitution mainly at C3 or C6 positions to give 3(6)-substituted derivatives. Nevertheless, nowadays some new synthetic procedures [3][5][6][7] have given the opportunity to prepare conjugated systems which include 1,8-, 2,7- or 9(3)-carbazolylene units. The

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• as one more example of electrophilic substitution in this series of scaffolds. In general, nitration of aromatic compounds, one of the well-known reactions, has a great significance for various fields of industrial chemistry, as it has been exploited extensively for large-scale processes, obtaining

• electrophilic substitution can occur in electron-rich (hetero)aromatic substituents of compounds 1 as a side reaction. In this relation, we have focused our efforts on finding suitable conditions for nitration of these compounds in order to incorporate nitro groups exclusively at C-2 and C-8, avoid side

• 6,12-dinitro-ICZs 9 are susceptible to electrophilic substitution at their terminal benzene rings, we have investigated bromination and formylation of derivatives 9a,b, and our hopes for regioselectivity of these reactions have proved to be justified. In particular, aldehydes 12a,b have been obtained

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• .) [1][2][3][4][5][6][7]. Since 1 is an electron-rich arene, aromatic electrophilic substitution seems to be the simplest method for this purpose, and a plethora of substituted pyrenes have been synthesized in this way [1]. As is shown in Figure 1, the most reactive in such reactions are positions 1, 3

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• xylenes, mesitylene, pseudocumene, or durene gave mixtures of oligomeric products. Probably, these products are formed through multiple electrophilic substitution reactions of these arenes by the reactive dication species D. When oxadiazole 1b reacted with tert-butylbenzene (Table 2, entry 10), product 2f

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• interesting chemical reactions of sydnones are their electrophilic substitution at C-4 and their participation in 1,3-dipolar cycloaddition reactions with olefinic and acetylenic dipolarophiles to form pyrazoles and functional transformation at C-4 [20][21][22][23][24][25][26]. Herein we present the synthesis

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• prepare tetrachloroparacyclophane, but a pure polysubstituted product is difficult to obtain by electrophilic substitution without repeated crystallization or chromatographic purification [9]. Thus, we report an improved synthesis method using the Winberg dimerization of 2,5-dichloro-(4-methylbenzyl

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• (path 2) reaction mechanisms for the formation of isoxazolines 3a–c as depicted in Scheme 3, in accordance with the proposed reaction mechanisms of heterocyclic enamines proposed earlier by Elliott and co-workers [36]. Path 1 includes the formation of intermediate A as a result of the electrophilic

• substitution of the β-H atom of the enamines 1a,b after treatment with hydroxamoyl chlorides 2a,d,g. The intermediate A undergoes cyclization to oxazolines 3a–c via addition of its hydroxy group onto the double bond of the enamine fragment. This kind of cyclization was ruled out by Elliott et al. [36] because

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• is also dependent on the kind of coupling compound used [31]. For example, phenols are successfully coupled in alkaline conditions in which the phenolate ion is formed. These conditions provide the desired electron-releasing group thus facilitating the electrophilic substitution reaction to afford

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• like the bis(1,1'-dimethyl-3,3'-methylenediimidazoline-2,2'-diylidene)palladium(II) dibromide [L2PdBr2] consists of three steps: electrophilic substitution, oxidation and reductive elimination involving a palladium(IV) intermediate [26]. But we also experimentally set out to investigate potential

• should be active according to the proposed catalytic cycle, which starts with an electrophilic substitution reaction. We therefore set out to synthesize the corresponding methyl complexes for the “hybrid ligand” with chloro- and trifluoroacetato ligands. Results and Discussion Synthesis Some time ago we

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• electrophilic substitution and cross-coupling reaction are in progress. Experimental General procedure for the preparation of compounds 3: CuBr (3.6 mg, 0.025 mmol, 5 mol %), (phenylethynyl)di-p-tolylstibane (1, 203 mg, 0.5 mmol), and an organic azide (2, 0.5 mmol) were dissolved in THF (5 mL). The reaction

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• C–H activation reactions. Palladacycle formation. The generation of cationic Pd(II) from Pd(OAc)2. Electrophilic substitution of aromatic hydrogen by cationic palladium(II) species. Attempted reactions of palladacycle 6. The impact of MeCN on C-H activation/coupling reactions. Stoichiometric MeCN

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• in useful yields. The highly defined nature of the intermediate lithiate anions is important to the control of these reactions. Thus, much wider ranges of products are observed if direct electrophilic substitution is used as an alternative strategy of host functionalization [24]. As well as proving

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• electrophilic substitution reaction, the occurrence of powerful new synthetic strategies such as transition metal-catalyzed C–H activation brought new opportunities to the synthesis of more diversely halogenated products by enabling the halogenation of more challenging substrates by more selective

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

• chain elongation of the bis-azulene derivative 76 with a four-carbon unit has been accomplished by electrophilic substitution with 4,4'-dimethoxybutan-2-one (77) under acidic conditions and subsequent elimination of methanol under basic conditions gave the advanced precursor 78 (28%). The

Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”

• Julio Benites,
• Juan Meléndez,
• Cynthia Estela,
• David Ríos,
• Luis Espinoza,
• Iván Brito and
• Jaime A. Valderrama

Beilstein J. Org. Chem. 2014, 10, 2448–2452, doi:10.3762/bjoc.10.255

• (1) with phenylamines using oxidants such as K3Fe(CN)6, HIO3 and NaIO4 in aqueous alcohol. According to these authors, the oxidative phenylamination mechanism involves a radical cation intermediate generated by an electron transfer process from the phenylamine to the oxidant. Further electrophilic

• substitution at the 4-position of compound 1 followed by oxidation of the aminonaphthol intermediate, yield the N-phenyl-1,4-naphthoquinone-4-imines. A mechanism involving radical cation intermediates is supported by the rather high product yields resulting from the reaction of 1,5-DHN (1) with electron-donor

Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione

• Vilas Venunath Patil and
• Ganapati Subray Shankarling

Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90

• -9,10-dione, which is highly deactivated towards the electrophilic substitution is investigated. The peracid, nonanebis(peroxoic acid), possesses advantages such as better stability at room temperature, it is easy to prepare and non-shock sensitiv as compared to the conventional peracids. The present

• aminoanthracene-9,10-dione deactivate the ring towards electrophilic substitution [11]. Generally, the bromination of aminoanthracene-9,10-dione is carried out in sulfuric acid [12][13][14][15] (20 to 98%) and nitrobenzene [16][17] at a high temperature (80 to 120 °C) with or without a catalyst (like Cu or CuSO4

• was surmised that in the presence of oxidant these substrates form a diimine type product (similar to oxidative hair dye mechanism) [33], which makes the ring unreactive towards electrophilic substitution. Since Oxone and 50% hydrogen peroxide showed good results with substrate 1a, we have checked the

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• reactions are fast and highly exothermic. Typically, the nitration of aromatic compounds is acid-catalyzed and it involves an electrophilic substitution where the nitronium ion (NO2+) acts as the reactive species [4][5][6]. Based on estimations of 2007 and the proposed world production capacity, the overall

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• electron-rich and neutral donor IPr ligand favors the latter cyclization against the former. On this ground, a change in the tethering element switching the linker from NTs to oxygen (Scheme 4A, X = O) results in more activated rings towards aromatic electrophilic substitution processes. To this respect

• moment. In this case, a demanding electrophilic substitution must occur and should produce very efficiently the 3-aurated-4-iodo-2H-chromene C and one equivalent of acid. Next, gold-assisted protonation at C-4 should afford D [57], an intermediate featuring a gold-carbene at C-3, that would require a

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• is known to have a high number of acidic sites in its porous structure [43]. They showed that among various readily available porous aluminosilicates like HSZ-360-Y, ZSM-5-Y, K10 montmorillonite, etc., HSZ-360-Y was capable of catalyzing the electrophilic substitution process. However, a rigorous

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• , the ability to synthesize these recognition units containing azobenzene units opens up the possibility to turn hydrogen bonding on and off. With regard to synthesis, aromatic azo compounds are commonly prepared by an electrophilic substitution reaction, the best partners being an electron-rich

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• at C4 having no partner to couple with. Thus the incorporation of bromine at C3 (Table 1, entries 2 and 4) was established. When 1b reacted with more than two equivalents of DD, the second bromine atom was incorporated in the carbocyclic ring at C8 through aromatic electrophilic substitution (Table 1

• result (Table 1, entries 10 and 11). It is important to note that the presence of an electron-donating group (–NH2) at C6, without an alkyl substituent at C4, lead to bromination of the carbocyclic ring bearing the amino group through aromatic electrophilic substitution instead of vinylic bromination

• efficiently as that at C7 through mesomeric delocalization. Rather, it was more capable of stabilizing the positive charge in the Wheland intermediate obtained after the electrophilic attack at C5, as shown in Figure 2. Thus, bromination at C5 and C7 occurred through aromatic electrophilic substitution of the

Computational evidence for intramolecular hydrogen bonding and nonbonding X···O interactions in 2'-haloflavonols

• Tânia A. O. Fonseca,
• Matheus P. Freitas,
• Rodrigo A. Cormanich,
• Teodorico C. Ramalho,
• Cláudio F. Tormena and
• Roberto Rittner

Beilstein J. Org. Chem. 2012, 8, 112–117, doi:10.3762/bjoc.8.12

• electron acceptor (QTAIM atomic charge of −0.620 for F against −1.093 for the hydroxy oxygen), which is not so uncommon, as stated in classical textbooks on aromatic electrophilic substitution, since a resonant structure with a C=F+ contribution can take place [31]; this is shown by NBO calculations, which

Structural conditions required for the bridge lithiation and substitution of a basic calix[4]arene

• Conrad Fischer,
• Wilhelm Seichter and
• Edwin Weber

Beilstein J. Org. Chem. 2011, 7, 1602–1608, doi:10.3762/bjoc.7.188

• decade two main preparative routes for the methylene-bridge substitution of p-tert-butyltetramethoxycalix[4]arene have been established: A protocol described by Biali et al. yields a stabilized methylene carbocation through bromination that is ready for electrophilic substitution under SN1 conditions [3