Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• the displacement of the chloro substituent with the allyl group, affording 21 in good yield. Electrophilic aromatic substitution reactions at the chloroalkyl ether site were possible when promoted by aluminium chloride, with anisole and diphenyl ether giving addition products 22 and 23 containing

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• bonds of unactivated aryls or aromatic sulfenylation by electrophilic aromatic substitution (SEAr) has also recently received attention [38]. In recent years, N-(aryl/alkylsulfenyl)succinimides and N-(arylsulfenyl)phthalimides have been widely employed as new alternative sulfenylating reagents in the

• the best of our knowledge there are no review articles focusing on the application of N-(sulfenyl)succinimides/phthalimides in sulfenylation reactions. In this context, we describe various sulfenylation reactions, such as electrophilic aromatic substitution, ring-opening, dehydrogenative cross

• nucleophilic trapping of the electrophilic SAr unit to furnish C2-sulfenylated product 65 and Co-complex IV. At last, active cobalt species I regenerated from IV in the presence of AcOH. It should be noted that when R = H, C2-sulfenylated product 65 may be sulfenylated via a thermal electrophilic aromatic

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• conjugated enones afford O,C-diprotonated forms under superelectrophilic activation conditions. These dications can participate in electrophilic aromatic substitution reactions with arenes ([11] and references therein). Recently, we have shown that the reaction of (E)-5,5,5-trichloropent-3-en-2-one [Cl3CCH

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -derived ketimines 49 was reported by Vila, Pedro and co-workers. Regioisomeric hydroxyquinolines were tested in this reaction to facilitate the electrophilic aromatic substitution on the ortho-carbon atom with respect to the hydroxy group in quinolines 15. The reaction affords oxindole scaffolds 116 with

• aromatic substitution involved isatin-derived ketimines 49 as the electron-demanding partner to achieve this aromatic p-C–H bond functionalization framing an all substituted stereocenter at the C3 position of the oxindole scaffold in the products 60. A very low reaction temperature (−55/−60 °C) was ideal

• -pyrrolyl, trifluoromethyl and alkynyl as other three substituents (Scheme 15c) [42]. In 2020, a completely para-selective aza-Friedel–Crafts protocol with N-monosubstituted aniline derivatives 59 catalyzed by the chiral phosphoric acid P19 was disclosed by Zhu, Zhang and co-workers [43]. The electrophilic

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• . In addition, the lone pair electrons of the nitrogen atom interact with Lewis acids instead of the π-electrons of the ring system thus resulting to its reduced reactivity for electrophilic aromatic substitution reactions, such as a Friedel–Crafts reaction [21][22][23]. Hence, it is challenging to

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• , the reaction of 4aa in DCE at 50 °C gave the product 5aa in 23% yield (Table 1, entries 1 and 2). A larger amount of TfOH turned out to increase the solubility of the product and therefore impeded the purification process. However, an excess of acid is required for the electrophilic aromatic

• substitution to take place. With 2.5 equivalents of TfOH as the optimum amount of acid the product 5aa was obtained in a yield of 69% (Table 1, entry 3). Similar results were observed with DCM at 40 °C (Table 1, entry 5). A higher amount of mCPBA did not lead to a better yield due to more washing required to

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• transformations of aryl substrates have also been reported for thiovinyl ethers, and also for dihydrodithiins (Scheme 5), although there are obvious limitations to this point of view. Classical electrophilic aromatic substitution procedures such as the Vilsmeier–Haack reaction or a simple nitration have been

• products (viz 16, Scheme 5b) [37]. Electrophilic aromatic substitution under less forcing reaction conditions of the same substrate 15, using a room temperature nitration procedure, does yield the expected mononitrated dithiin 17 in good yield, without desulfurization [38]. 1,4-Dithiin-2-carbaldehyde (18

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• synthesized from 2-aminobiphenyl according to the literature [47]. Subsequent reaction with phosphorus trichloride and electrophilic aromatic substitution gave a chlorophosphine intermediate, which was directly reacted with (S)-1-phenylethylamine, then hydrogen peroxide. Phosphonamide diastereoisomers 17 were

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• addition of 1.1 equiv of NBS afforded a mixture of products with reduced regioselectivity to the expected p-bromophenol (yield: 62%). From the mechanistic point of view, it is expected that a standard electrophilic aromatic substitution pathway was followed for the halogenation using NXS (X = Br, I, or Cl

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• ; N-halosuccinimide; palladium(II); Introduction Electrophilic aromatic substitution [1][2][3] and ligand-directed transition-metal-catalyzed reactions [4][5][6][7][8] are among the most widely used synthetic approaches for the preparation of halogenated arenes. They are important precursors in cross

• in the para position occurred in the absence of the added PdII catalyst and additives, in the ortho position to the substituent, which is typical for the products of electrophilic aromatic substitution. In addition, an additive- and solvent-free protocol without the added PdII catalyst was developed

• azobenzenes with strong electron-donating groups was carried out without an added PdII catalyst. These transformations, which take place via electrophilic aromatic substitution, resulted in products halogenated in the ortho position to the electron-donating groups. The reactions of azobenzenes containing a

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• approaches toward such compounds have been developed. Among these, cyclization and annulation of 3,5-unsubstituted, 4-substituted indoles involving an electrophilic aromatic substitution (SEAr) as the ring closure are particularly attractive, because they avoid the use of 3,4- or 4,5-difunctionalized indoles

• summarizing recent relevant literature reports. Keywords: annulation; cyclization; fused indoles; regioselectivity; SEAr; Introduction Over the decades, countless cyclization and annulation reactions of substituted arenes/heteroarenes involving an electrophilic aromatic substitution (SEAr) reaction as the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• examining of other potential arenes capable of undergoing electrophilic aromatic substitution would expand the applicability of the reaction. Carboazidation In 2018, Yang investigated the three-component carboazidation of styrene derivatives 115 with alkanes 101/139b and trimethylsilyl azide for the

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• methods, which provide active ingredients to prevent or reduce the effects of oxidative stress in cells. Recently, our research group reported the synthesis of 6-amino-4-(trifluoromethyl)quinolines, which were obtained through an electrophilic aromatic substitution reaction catalyzed by sulfuric acid from

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• AlBr3 to both the nitrile and acetylene bonds of the starting compound 1 furnishes the highly electrophilic species A bearing a positive charge on the acetylenic carbon atom C3. The subsequent reaction of species A with the arene molecule via electrophilic aromatic substitution results in the formation

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• development of efficient methods to access multifunctional ferrocenes has attracted tremendous attention. Conventionally, functionalized ferrocenes were derived via electrophilic aromatic substitution mediated by strong Lewis acids or direct metalation using strong bases, such as alkyllithium reagents [3][9

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• aromatic substitution reaction. The substrate failed to give the same product when subjected to alkylation with the isolated putative iminium ion intermediate. The authors then suggested the reaction took place through a radical mechanism instead. This vanadium-mediated aminoalkylation reaction was found

• heteroaromatic electrophilic substitution and a non-radical pathway. An aminomethylation of the heteroaromatic ring with N-methylmorpholine-N-oxide catalyzed by VO(aca)2 reported by Mitchell and co-workers [109], however, was found to undergo with a regioselective outcome incompatible to an electrophilic

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• in determining ring closure either via path a or path b. In path a, the protonation of the imine nitrogen in 7a by the conjugate acid (+ BH) leads to an electrophilic aromatic substitution at the 3-position of the indole unit to form a carbon–carbon bond in the intermediate 8. A further proton

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• the chemistry of naphthalene. The last one dates from 1887 and deals with the formation of isomers in the electrophilic aromatic substitution of naphthalene with chlorine and bromine [32]. This work was done in collaboration with Pietro Biginelli (1860–1937), the only collaborator of Guareschi who

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• expand the library of derivatives containing core structure 13, electrophilic aromatic substitution of this compound was explored (Scheme 2). Nitration of 13 using 70% nitric acid in glacial acetic acid gave the corresponding regioisomers 14 and 15 in 53% and 41% isolated yield, respectively. The 1H NMR

• . Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13). Synthesis of isomeric oxazole-fused derivatives. Fused derivatives from 16. Supporting Information Supporting Information File 164: Experimental part as well as 1H and 13C NMR data. Funding We thank the KU Leuven for financial

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• of pyrroles to the 3,4-disubstituted derivatives is challenging because an electrophilic aromatic substitution of pyrroles or the metalation of N-substituted pyrroles and the subsequent reaction with electrophiles take place in position two of the ring [6][7]. Recently, N-sulfonyl-1,2,3-triazoles

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• obtained with DeoxoFluor at elevated temperature (Scheme 2). A side-product in this fluorination reaction was the tricyclic compound 12, which presumably formed through an electrophilic aromatic substitution reaction of the activated alcohol intermediate. The inclusion of TMS-morpholine [29] reduced the

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• crystal of sumanene derivative 82 by means of time-resolved microwave conductivity technique. On the other hand, four years later, Sakurai and his teammates have reported the selective synthesis of diverse monosubstituted sumanene derivatives by employing electrophilic aromatic substitution reactions as

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• °C, 19F NMR monitoring of the reaction’s progress indicated the appearance of a second product beside the 1,4-cyclohexadien-1-iminium salt 4-Ch. Further investigations revealed that the new product was the dihydrofluorene 7, resulting from 4-Ch by an intramolecular electrophilic aromatic substitution

• propyn-1-iminium ion via its C3-position to the olefinic bond of styrenes initiated a reaction cascade which was again terminated by the already mentioned cyclization step through intramolecular electrophilic aromatic substitution, resulting in the formation of 2-(1-phenylvinyl)-1-(trifluoromethyl)-1

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• . The developed methodology is capable of predicting reactivity of various substrates by differentiation between two major mechanisms – proton abstraction and electrophilic aromatic substitution. An attempt has been made to predict new C–H activation reactions. This methodology can also be used for the

• was proposed for classifying whether the carbon atoms are active or inactive toward electrophilic aromatic substitution [17]. Also, a quantum mechanical approach was introduced to compute ortho-directing groups (DGs) in palladium-catalysed aromatic C–H activation reactions [18]. However, there is a

• : a) electrophilic aromatic substitution (SEAr) mechanism and b) proton abstraction (PA) mechanism. The key step for the electrophilic aromatic substitution is an electrophilic attack by Pd(II) onto the aromatic substrate that also defines the regioselectivity of the overall process [24]. The key

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• ][8]. Every student of organic chemistry is taught the importance of arenium ions in the classic two step SEAr mechanism for electrophilic aromatic substitution. Addition of an electrophile to an arene leads to a bound species, sometimes called a σ-complex, which then loses a proton at the site of