Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• which their observed relative dienophilic reactivities could be rationalized. Besides, the Fukui functions of the carbon/nitrogen and phosphorus atoms of the >C=P– and –N=P– functionalities were also computed which revealed their hard electrophilic character and accorded well with the dienophilic

• calculate various reactivity descriptors, such as electrochemical potential, electrophilicity and nucleophilicity indices, global hardness, electronegativity, etc. The concept of hard–soft acid–base (HSAB) was used to explain the reactivity of the organic molecules towards electrophilic and nucleophilic

• reagents [19]. Thus a quantitative descriptor, the Fukui function was defined as for nucleophilic attack and for electrophilic attack, where ρN+1(r), ρN(r), and ρN−1(r) are the electron densities at a point r in the system with N+1, N, and N−1 electrons, respectively, all with the ground-state geometry

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• containing an unsubstituted cyclopropane ring (1) or bearing Me (2) and COOMe (3) groups were obtained using previously reported protocols [15][19]. Complex 4 is new. Compound 4 was obtained by the reaction of an electrophilic dehydroalanine complex with a bromomalonate anion (Scheme 1). The reaction

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• addition, radical cation addition, and electrophilic aromatic addition, have also been proposed [1][10][29]. A proposed mechanism is depicted in Scheme 2: First, the hydroxy group on the A- or B-ring is converted into a radical by a P450-induced single-electron transformation. The resulting radical then

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

• , the optimal reaction conditions for the electrophilic monobromination was set as to grind the substrates (1 mmol) in an automated grinder with 1.1 mmol of NBS at 100 rpm in PEG-400 (0.2 mL per mmol of the substrate) as a grinding auxiliary. We next explored the substrate scope of the catalyst-free

• observed for 4-phenylphenol indicating this electrophilic halogenation is selective to electron-rich aromatic rings only (product 2f, Scheme 3). Also, aromatic halogenation prevails over α-halogenation of a ketomethyl group as was demonstrated by the formation of product 2m as the sole product for the

• just 2 min of grinding (products 2q and 2r, Scheme 3). Next, a series of aniline derivatives were taken as the substrates for this electrophilic bromination by NBS. To our delight, the corresponding bromo derivatives were formed in high yields (75–89%) within 5–15 min of grinding (products 2s–y, Scheme

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• atom is reversed (umpolung) from electrophilic to nucleophilic (Scheme 3). This approach can be exploited in many organic reactions, such as: the benzoin condensation [16][17], esterification and amidation of benzaldehydes and cinnamaldehydes [18][19], synthesis of γ-butyrolactones [20], synthesis of

• [33]. Flow electrochemistry was applied to oxidize the Breslow intermediate to the corresponding electrophilic acylthiazolium intermediate, which then functioned as an acyl-transfer reagent, reacting with alcohols or amines. To the best of our knowledge, only one research group reported the cathodic

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• amine) on the most electrophilic component of the α-ketoaldehyde (its aldehyde) to give intermediate 5. However, the ensuing cyclization (via a hydration of its imine bond to allow for a rotation) would then lead to compound 4 which is rarely the major reaction product. Since compound 3 is the main

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• , it was observed that the MBH reaction of 6b with acrylonitrile A resulted in the formation of product 8bA which evidenced that 6b underwent Morita–Baylis–Hillman reaction at the electrophilic carbonyl center as well as Michael addition reaction at the nucleophilic nitrogen center (N-9). Similar

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

• proceed due to their reduced nucleophilicities, generating the corresponding phosphonamidates only through the reaction with the more electrophilic phosphonochloridate (Scheme 32) [57]. [4 + 1] Annulation via formations of both C–P and P–N bonds (1S,3R)-2-(tert-Butyldiphenylsilyl)-3-methyl-1-phenyl-2,3

• ortho-directed lithiation with tert-butyllithium with carbamate as the directing group followed by electrophilic quench with methyl chloroformate and intramolecular aminolysis. Finally, hydrolysis removed the directing group, affording the final product 239 in 50% yield (Scheme 38) [59]. Structurally

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• olefins in moderate yields [5]. Prakash et al. also achieved fluoride-induced nucleophilic (phenylthio)difluoromethylation of carbonyl compounds using PhSCF2SiMe3 [6]. Quite recently, Shen et al., developed various nucleophilic, electrophilic, and radical difluoromethylthiolating reagents [1]. However

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• , it is essential to explore the mechanisms. Welch et al. supposed that the strong electrophilic Lewis acid triggers charge transfer with nitrogen-containing heterocycles containing lone-pair electrons. Consequently, it reduces the electron density of the π-conjugated system and the characteristics of

• the addition of suitable Lewis acids can lead to a dramatic red-shift in the absorption and emission of the mixtures. The electrophilic Lewis acid as electron acceptor frequently reacts with the nitrogen-containing heterocyclic conjugated molecules, ascribed to the charge redistributions of the

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , trifluoromethyl radicals and its longer-chain analogues, share a common electrophilic character and a stabilizing stereoelectronic effect [14], we envisioned that the “dummy group” methodology could be translated into the formation of sought after perfluoroalkyl radicals (Scheme 1). In this work, we report the

• perfluoroalkylsulfinates 2 and halogenated electrophilic partners. Left: isolated yields of synthesized perfluoroalkylating reagents: perfluorobutyl (1a), perfluorohexyl (1b), and perfluorooctyl (1c) analogues (after conversion of byproduct); middle: gram amounts of perfluorooctyl product 1c; right: UV–vis absorption of

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

• proceeds by electrophilic cleavage with neutral NBS or the hydrogen bond complex NBS∙∙∙TsOH as a bromine source. Here we present the mechanochemical selective halogenation of unsymmetrically substituted azobenzenes by NXS (X = Cl, Br, or I). The liquid-assisted grinding of para-halogenated derivatives of

• 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

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