DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• reaction. So, based on literature reports [53][54][55], we have proposed a reaction mechanism in Figure 5b. Initially, DDQ abstracts a hydride ion from substrate 1a to generate the intermediate A. Then intermediate A undergoes an electrophilic intramolecular cyclization to form the cationic intermediate B

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• -Elimination of an azole from A leads to formation of an isolable diene B. Upon further heating, the amino group attacks the electrophilic C–Cl position of the trichlorovinylic group intramolecularly, leading to a 2,3-dihydro-1H-pyrazole C. Finally, pyrazoles 3 are obtained upon 1,3-elimination of hydrochloric

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• anion binding property and potent electrophilic activation ability [31][32][33][34][35][36]. To incorporate extra functionality, tertiary amine groups can be also embedded as Lewis base sites for realizing electrophilic/nucleophilic cooperative catalysis [37][38][39]. For this purpose, one kind of

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• -trisubstituted isoxazoles (Figure 1) [21][22]. Similarly, palladium catalysts were used for the electrophilic intramolecular cyclization of alkynes and aldoximes to produce 3,4,5-trisubstituted isoxazoles, but the scope of the substrates of the method was limited as the substituted 2-alkyne-1-one O-methyl oximes

• thermodynamical product. The solvent polarity also affects the keto–enol equilibrium of the intermediate II-D. In polar solvents, the keto tautomer is predominant as an electrophilic group for the intramolecular cyclization, while in nonpolar solvents, the enol tautomer could not accept a nucleophilic attack for

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• electrophilic bromination of the corresponding phenol, followed by hydrolysis promoted by H2O2 [66]. Variations in the methods of 2-methylnaphthol (17) oxidation to menadione (10) with H2O2 were made by changing the catalytic systems in order to increase the yield and selectivity. These include the catalysis by

• aldehydes and ketones [128]. In this context, Fry and co-workers explored the electrophilic substitution reaction to synthesize 2-methyl-3-bromonaphthalene-1,4-dione (82), an important intermediate used for the synthesis of naphthoquinones functionalized with organochalcogens [127]. Compound 82 was obtained

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• based on Diels–Alder reactions of cyclopentadiene with alkynes [13][14][15][16][17][18][19][20][21][22][23]. However, since this synthetic route requires strongly electrophilic alkynes, its scope is limited to products that contain at least one electron-acceptor group, such as an ester, a nitrile or

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• intermediate spontaneously turns into the carbanion C, thus realizing the imine umpolung and allowing the cross-coupling reaction with the remaining electrophilic ketimine 1. The complete diastereoselectivity would arise from the mutual approach of the two oxindole nuclei from the less hindered side, that is

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

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• salts tested Fe(III) acetylacetonate seemed to be the best catalyst. In order to outstretch the scope of the reaction phenylacetylene was coupled with various electrophilic partners. Liu et al. developed a catalytic system for the cross-coupling of aryl iodides with alkynes by the use of a combination

• catalytic efficiency than other catalytic systems. For studying the efficiency of the catalyst, they selected the reaction of 4-iodonitrobenzene and phenylacetylene in the presence of 0.5 mol % of Fe2O3 nanoparticle as catalyst and K2CO3 as base in ethylene glycol at 80 °C. Both, the electrophilic character

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• -annulated tetrazines. These compounds, bearing a large number of heteroatoms in their structures, have additional opportunities for non-covalent bonding with a variety of biological targets. In addition, a high electrophilic character of the tetrazine ring can provide chemical binding to pathogenic objects

• reaction of 7-methyl-substituted triazolotetrazine 3a with ethyl cyanoacetate, a rather complicated mixture of several products has been obtained, none of the latter failed to be isolated in a pure form. Thus, it has been shown that new triazolo[1,5-b][1,2,4,5]tetrazines retain electrophilic centers

• ][1,2,4,5]tetrazines has been developed. A comparative analysis of their reactivity and fungistatic activity relative to isomeric [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazines has been performed. It has been shown that new derivatives retain the electrophilic character and the reactivity pattern in the

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• TFE replaced by the even more electrophilic 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) component. The 97% TFE has a YCl value (for interaction at chlorine) of 2.83, which increases to 5.08 on going to 97% HFIP [25], corresponding to a considerable increase in its ability to interact with, and assist in

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• alkoxycarbonylketenes, which undergo an electrophilic ring expansion with aziridines to afford alkyl 2-(oxazolin-2-yl)alkanoates in good to excellent yields under microwave heating. The method is a convenient and clean reaction without any activators and catalysts and can be also applied in the synthesis of 2-(oxazolin

• alcohols [13][14][15] (Scheme 1a); (3) oxidative condensation of aldehydes with vicinal amino alcohols [16] (Scheme 1b); (4) cyclization of N-allylamides in the presence of electrophilic reagents or radical initiators or catalysts [17] (Scheme 1c); (5) direct synthesis from alkenes and amides or nitriles

• in the presence of electrophilic reagents [18][19] (Scheme 1d). Aziridines can be considered as the NCC structural fragment after ring-opening and have been applied in the synthesis of aziridine-imine-containing chiral tridentate ligands [20], 2-alkylideneoxazolidines [21], and N-vinylamides [22]. We

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• and earth abundant characteristics. Moreover, much greener methodologies like microwave-assisted cyanation reactions also received much attention in recent times [21]. The cyanation can be carried out using electrophilic and nucleophilic cyanating agents [22]. Usually a cyanation is accomplished via

• the nucleophilic attack of a CN− at an electrophilic carbon center. But there are some reagents that react as CN+ and thus attack the nucleophilic carbon center. Tosyl cyanide [23], 2-chlorobenzylthiocyanate [24], and cyanogen chloride [25] are some of the examples for electrophilic cyanating agents

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

• is the termination of the reaction through the trapping of the reactive intermediate. Organoiron complexes have been shown to undergo electrophilic trapping with external species or proceed through cross-coupling eventually undergoing reductive elimination. Radical addition will typically conclude

• generated. This is where sequential and nonsequential CDC reactions diverge. In the case of a nonsequential CDC reaction, the alkyl radical will directly attack an electrophilic species [79]. On the other hand, sequential CDC reactions involve propagation reactions. These propagation steps typically involve

• electronic properties of the alkenes to control the chronology of the additions. The rate of addition of the acyl radical to an electro-deficient alkene is about three times greater than that of a styrene derivative [109][110]. The electrophilic radical, adjacent to an EWG, will favor the subsequent addition

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

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

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of them (pathway a) includes the formation of the nitrene cation 11 [41][42][44][45][53] under action of PIFA as an oxidant. A subsequent electrophilic attack at the double bond provides aziridinium cation 12 that undergoes selective ring opening with the trifluoroacetate anion to give intermediate

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• homoallylic position that assists the electrophilic attack on the double bond [33][34]. The protection of the homoallylic hydroxy group in similar alkenyl diols in epoxidations with the VO(acac)2/t-BuOOH system led to the formation of the erythro isomer [35]. Actually, highly stereoselective epoxidations of

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• of isoquinoline N-oxides [41][42], condensation of lithiated o‐tolualdehyde tert‐butylimines with nitriles [43], electrophilic cyclization of 2-alkynylbenzamides [44][45] or 2-alkynylbenzaldoximes [46][47][48][49][50][51][52][53][54], oxidative C–H functionalizations (coupling) on aryl and heteroaryl

• synthesis of a wide array of heterocyclic compounds by creating C–C, C–N, C–O and C–S bonds due to their ability to act as electrophiles. The cyano group is considered as a versatile functional group in various organic syntheses because of its participation in various electrophilic, necleophilic and bipolar

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ]. Organocatalytic aryl C–H activation via a nonradical process represents an enormous challenge in organic synthesis, although the nucleophilic aromatic substitution with cleavage of the electrophilic aryl C–H bond has only recently been developed by transition-metal-catalyzed aryl C–H activation [57]. In the

• diarylamines that exist as rapidly interconverting atropisomers, and a VEGFR inhibitor from Wyeth contains a potentially atropisomeric N-arylquinoid [95][96]. In 2020, Gustafson and co-workers reported the first chiral phosphoric acid-catalyzed atroposelective electrophilic halogenation of N-arylquinoids 95, a

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• highly electrophilic N-acyliminium intermediates [17]. As a special aspect, we used a carbamate unit (instead of the commonly used carboxamide), ending up with 1-benzyl-1,2,3,4-tetrahydroisoquinolines bearing an N-ethoxycarbonyl residue, which in turn was easily converted directly into an N-methyl group

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• amines 2c, 2d, and 2f, albeit in drastically lower yield (Table 1, entries 3, 4, and 6). Initially, our focus was on testing tertiary amines, as we speculated that the electrophilic iminium species 4a (R1, R2 = alkyl; Scheme 3) would form more easily with stabilizing electron-donating alkyl substituents

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

• take part in electrophilic [1][2] and nucleophilic [3][4][5][6] addition reactions onto the acetylene bond leading to various substituted nitriles. Reactions onto both acetylene and nitrile groups are widely used for the construction of various heterocyclic systems [7][8][9][10][11][12][13][14][15

• our work on electrophilic transformations of alkynes [18][19][20], we investigated reactions of 3-arylpropynenitriles under electrophilic activation conditions (see [21] for the chemistry of superelectrophilic species). The goal of this work was to study the reactions of 3-arylpropynenitriles with

• incomplete conversion of the starting compound 1a and a low yield of the target product 2a (<10%). The yields of the compounds 2 were moderate (20–64%) that may be caused by possible transformations of the nitrile group in the electrophilic medium leading to oligomeric material [22]. The reaction proceeded

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• bifunctional pyrrolidine-containing sulfinylureas and thioureas. These catalysts operate via enamine activation of aldehydes and hydrogen-bond activation of the electrophilic component, in this study – nitrostyrenes. These catalysts were effective in the Michael addition of aldehydes to nitroalkenes, affording

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• synthetic utility, we surmised that replacing the aroyl component of the N-phenacyl substituent by electrophilic groups such as esters, amides or nitriles might yield 2,3-dihydro-1H-pyrrolizin-6-ones 13 or their hydroxypyrrole tautomers 13’. Our findings with N-(ethoxycarbonylmethyl)enaminones 14 are

• . Firstly, the E-geometry of reactant 15a is obviously incorrect for the cyclization, which requires the nucleophilic methylene adjacent to the ester to approach close enough to the electrophilic carbonyl group of the enaminone for the intramolecular condensation to occur. It is possible that acid-induced

• reaction in the same solvent gave high yields of pyrrolo[2,1-b]thiazol-6-ones [56]. The former results from reaction between the α-methylene position of the ester and the electrophilic carbonyl component of the enaminone, while the latter arises from nucleophilic attack of the enaminone at the ester’s