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

• -rich arenes (Scheme 1, top) [34][108][109][110][111][112][113][114][115][116][117][118][119]. In other arrays, particularly those with more electron-rich substituents, evidence suggests an electrophilic aromatic substitution mechanism may be operative. In these instances, electron-poor catalysts, such

• -methoxycarbonylphenyl iodide, for example, gave a low yield of product 3k. Arylureas having only an electron-withdrawing group showed no reactivity towards coupling under either set of conditions (3x), consistent with an electrophilic aromatic substitution pathway in the initial C–H activation step by a cationic

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• . The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and

• nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four. Keywords: direct fluorination; fluorine; nucleophilic aromatic substitution; pentafluorosulfanyl group; vicarious nucleophilic substitution; Introduction Organic compounds with a

• fluorodenitration of known 3,5-dinitro-1-(pentafluorosulfanyl)benzene (5) [10][28]. The reaction with TBAF hydrate resulted in clean substitution of only one nitro group for the fluorine atom (Scheme 4). Nucleophilic aromatic substitution of fluorine leading to compounds 3 was investigated (Table 1). With low

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• demonstrated that 4 can be elaborated in a relatively straightforward manner by mainstream reactions of electrophilic aromatic substitution [7]. This extended to the synthesis of cyclohexane substituted (S)-L-phenylalanines with orthogonal protecting groups suitable for their incorporation into peptides [8

• -tetrafluorocyclohexane motif has been incorporated in a range of products prepared from aryl iodides 5–7. These derivatives derive from aryl carboxylation or carbonylation, and complement those that can be prepared directly by electrophilic aromatic substitution of phenyl derivative 4. This chemistry should more readily

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• -carbenoid in the C3-position of N-methylindole followed by elimination of bromide. The conjugated iminium ion is a very good electrophile and can undergo an electrophilic aromatic substitution in the C3-position of N-methylindole to form the bisindole product. Conclusion We have developed a mild and

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• allenes catalyzed by PPh3 [22] (Scheme 1a–c). On the other hand, studies on the synthesis of 3-nitrothiophenes are scarce. One of the traditional methods involves electrophilic aromatic substitution reactions of thiophenes, which introduces substituents at the 2- and 5-positions, but with some drawbacks

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• 30 is estimated to be ca. 1000 times higher than that of the neutral fiber (before doping: σrt 3 × 10−6 S cm−1, after doping: σrt 3 × 10−3 S cm−1) [68]. Star-shaped pyrrole-fused TTF oligomers 38–43 were synthesized by nucleophilic aromatic substitution (SNAr) reactions of fluorinated benzenes with

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• a glycoluril-based framework possessing quinone moieties for developing a Diels–Alder cycloaddition strategy. Thus compound 12 [33] was prepared in 73% yield by treatment with an excess of hydroquinone in 1,2-dichloroethane using a Friedel–Crafts alkylation as an electrophilic aromatic substitution

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• – the ligand of coordination complex 2b. The synthesis of compound 10 – the ligand of coordination complex 2c – started by nucleophilic aromatic substitution of fluorinated pyridine 7 with compound 6 to receive a mixture of products 8 and 9 (Scheme 2). Purified compound 8 was then coupled with

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• electrophilic aromatic substitution at the 2-position of the N-aryl moiety. (The isolation of enone 8a and the fact that 5a does not react with oct-1-ene under the same conditions rules out a Diels–Alder-type pathway to 8b.) Formation of side-products 7a and 7b can be rationalised by dimerisation of allylzinc

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

• 1980s, Leardini et al. [15] have shown that under radical conditions via a homolytic aromatic substitution route diaryl-imines were suitable precursors to a number of 6-arylphenanthridine derivatives. The reaction proceeded by initial imidoyl-H atom abstraction by the electrophilic iPrO• radical, and

• eliminated the imine-H and formed the imidoyl radical, added to the phenyl ring. The homolytic aromatic substitution was terminated by H-atom abstraction by another t-BuO• radical. Among very few routes targeting the synthesis of 5,6-unsubstituted phenanthridines, the here presented radical-based pathway

• [22]. Starting from the similar isonitrile structure, 6-aroylated phenanthridines via base promoted homolytic aromatic substitution (BHAS) can be prepared [23]. Several photoinduced synthetic procedures were also applied. For instance, the photochemical cyclization of N-benzylanilines was used for

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

• aromatic substitution by using 2-fluoro-5-nitrobenzaldehyde (11b) to give rac-5 containing a tertiary arylamine nitrogen in 71% yield. With the 2-chloro-5-nitrobenzaldehyde reagent, only 3% yield for rac-5 could be achieved. Subsequently rac-5 was reacted with 1,3-dimethylbarbituric acid (12), Meldrum’s

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• ; Introduction Starting with their discovery in 1949, the [2.2]paracyclophane molecule and its derivatives have been intensely studied [1][2][3]. Of particular interest are the geometry and transannular interactions of these molecules, the study of electrophilic aromatic substitution reactions involving these

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• inhibitor library generation programme. Results and Discussion Our retrosynthetic approach introduces the diversity point at a late stage and takes advantage of the heterocyclic lactam present in PreQ0 after activation and subsequent nucleophilic aromatic substitution. This convergent synthesis allowed us

• ] (Figure 3). The resulting pivalamide 8 proved to be more soluble than 1 and the subsequent halogenation step was accomplished in the presence of a phase transfer catalyst, affording the desired chloro-intermediate 9 in fair yield. In our hands, nucleophilic aromatic substitution on 9 using amines of

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• ester is utilised as a building block for the synthesis of 2-fluoro-2-arylacetic acid and fluorooxindole derivatives by a strategy involving nucleophilic aromatic substitution reactions with ortho-fluoronitrobenzene substrates followed by decarboxylation, esterification and reductive cyclisation

• elemental fluorine for the key construction of the carbon–fluorine bond by complementary direct selective direct fluorination [41][42][43][44], continuous flow [45][46][47][48][49] and building block [50] strategies, in this paper, we describe nucleophilic aromatic substitution reactions of carbanions

• -fluoronitrobenzene (2a) led to the efficient displacement of fluorine by a nucleophilic aromatic substitution process to provide diester 3 in good yield (Scheme 1). Displacement of fluorine from ortho-fluoronitrobenzene was quantitative as measured by 19F NMR spectroscopy of the crude reaction mixture and the

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• study on the direct consequences of these three major factors for the outcome and mechanism of several recently reported eosin Y-catalyzed aromatic substitution protocols starting from arenediazonium salts [15][16][17][18][19][20][21]. Results and Discussion Effect of pH on the efficiency of eosin Y

• different mechanisms in these aromatic substitution reactions with arene diazonium salts. The redox potentials of most substituted arene diazonium salts cluster with very little deviation around 0.0 V vs. SCE (±0.2 V) [23][24] so that the observed differences in Φ can be largely attributed to different

• erosion of Φ. Conclusion In summary, we have investigated the impact of several reaction parameters on the outcome and mechanism of photocatalytic aromatic substitution reactions of arenediazonium salts in the presence of eosin Y. However, the significance of these data certainly extends to other light

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• C=C bonds modified. On the other hand, functionalization on the rim of circumtrindene can be achieved by normal electrophilic aromatic substitution, the most common reaction of planar PAHs. This peripheral functionalization has been used to extend the π-system of the polyarene by subsequent coupling

• used to functionalize the existing polyarenes and/or to extend them to larger PAHs. The most common class of reactions is the electrophilic aromatic substitution; however, free radical, nucleophilic addition, reduction, and oxidation reactions are also possible. To synthesize larger PAHs that are not

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• and Diels–Alder cascade. Concomitant electrophilic aromatic substitution and dehydration resulted in isoquinoloquinoline derivatives [22]. Similarly, isoindoloquinolines were also synthesized via classical Povarov chemistry between furyl aldimines and tert-enamides followed by a N-acryloylation, Diels

• the same fate of condensation without further electrophilic aromatic substitution. Lu et al. [43] have recently reported the synthesis of 3-(1-alkenyl)isoindolin-1-ones from N-acyliminium cations; however, their intermediates did not have the opportunity for intramolecular cyclization. The nitrogen

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• , Portugal 10.3762/bjoc.10.54 Abstract Three new porphyrin aminoalkyl dibenzylphosphoramidates were synthesized by nucleophilic aromatic substitution of one p-fluorine atom of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPPF20) by primary aminoalkyl dibenzylphosphoramidates. The nucleophilic aromatic

• investigate the direct hydrogenation of TPPF20 with H2 in the presence of 10% Pd/C. Results and Discussion Synthesis of porphyrin dibenzylphosphoramidates 1 The method [4] for the nucleophilic aromatic substitution of the p-fluorine atoms of TPPF20 under reflux in toluene/triethylamine did not work in

• substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• tripeptide byproduct. Nucleophilic aromatic substitution (SNAr) chemistry contributes to creating useful materials. In 2005, Comer and Organ reported SNAr reactions of 2-fluoronitrobenzene using a flow microreactor system with microwave irradiation (Scheme 9) [69]. Toward making compound-libraries, Schwalbe

• , followed by two kinds of library diversification involving 1) Michael addition of a set of primary amines and the subsequent nucleophilic ring closure to give the difluoroquinolone system, 2) intermolecular nucleophilic aromatic substitution with various amines and hydrolysis of ester moieties to afford a

The renaissance of organic radical chemistry – deja vu all over again

• Corey R. J. Stephenson,
• Armido Studer and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 2778–2780, doi:10.3762/bjoc.9.312

• homolytic aromatic substitution (BHAS) [3], b) photoredox catalysis [4][5][6][7][8], c) redox chemistry using Bu4NI in combination with t-BuOOH [9], d) transition metal catalyzed processes where radicals are suggested to interact directly with copper, nickel, zinc, palladium, gold and so on [10][11][12][13

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

• from the bacterial cell. Due to the elaborate substitution pattern of the parent quinolone ring systems these compounds are usually prepared via a linear consecutive sequence. In the case of moxifloxacin, an intramolecular base catalysed nucleophilic aromatic substitution is used to prepare the

• pyrimidines form very tight hydrogen-bonding arrays as seen in DNA and RNA. Synthetically, the electron-poor nature of pyrimidines accounts for the manifold functionalisation pathways using nucleophilic aromatic substitution chemistry. Electrophilic aromatic substitution reactions are more common during the

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

• pattern is not the one commonly associated with conventional electrophilic aromatic substitution reactions, other mechanism should not be disregarded on the basis of the structure of the final product. So, the alternative mechanistic description summarized in Scheme 4B cannot be firmly rejected, at the

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• -defficient character of this heterocycle. An electrophilic aromatic substitution at the C-5 of a pyrimidine is usually difficult [1][3][4][5]. However, the presence of two or three activating groups leads to the successful introduction of an electrophile (Scheme 1) [1][6][7][8]. On the other hand

• , nucleophilic aromatic substitution reactions of halopyrimidines are smooth and high-yielding, especially when an electron-withdrawing group is present in this heterocycle. It is noteworthy that in the case of non-activated dihalopyrimidines, the first nucleophilic displacement reaction deactivates the

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• indanes or dihydrobenzofurans are too slow to be useful synthetically. Keywords: aromatic substitution; computational chemistry; DFT-D3; free radical; polar effects; radical reaction; Introduction The development of efficient catalytic reactions is one of the central issues of chemistry [1][2]. Radical