Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• mechanistic strategies, namely, electrophilic, radical and nucleophilic approaches, and highlighted when emerging technologies, such as photo- and electrochemistry effect the desired transformation [22][27]. Review Electrophilic benzylic C(sp3)–H fluorination Base mediated Electrophilic fluorinating reagents

• subsequently attack electrophilic Selectfluor to afford the benzyl fluoride (Figure 2) [34]. The methodology was demonstrated on eight para-substituted benzylic substrates. The authors noted that resubjecting the monofluorinated compound 1 to the same reaction conditions afforded the difluorinated compound 2

• monofluorination radiolabelling using [18F]NFSI. Electrophilic fluorination of benzylic C–H bonds has been demonstrated as a powerful approach. However, these techniques can be constrained to defined substrate classes and the requirement of using strong bases. Palladium catalysis Palladium-catalysed chemistry is

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• addition, the recent years have seen remarkable progress in utilizing electrophilic azide-transfer reagents, i.e., hypervalent iodine-based compounds, for (asymmetric) α-azidations [16][17][18][19][20][21][22][23]. Besides these valuable approaches, which either require appropriate pre-functionalization of

• the starting materials (nucleophilic approach), or rely on more advanced N3-transfer agents (electrophilic approach), over the course of the last years also α-azidations of enolate-type precursors using nucleophilic azide sources under oxidative conditions have been introduced very successfully [24

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• reduction. This electrophilic aromatic substitution usually needs harsh reaction conditions, tedious synthetic procedures and sometimes encounters the trouble of separating positional isomers caused by orientation or steric effects of the pre-existed amino group on the aryl moiety. Nevertheless, anilines

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

• study, benzonorbornadiene (1a) and the chiral natural product (+)-camphene (1b) were used as bicyclic alkenes. Safe, easily soluble, easy to use, stable solid, reactive and commercial available selectfluor [18][27][28] was selected for electrophilic fluorination source. Water and various alcohols were

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• oxidant. This metal-free approach was postulated to involve the in situ generation of reactive thio/selenocyanogen chloride (Cl–SCN/SeCN) from the reaction of PhICl2 and NH4SCN/KSeCN, followed by an electrophilic thio/selenocyanation of the pyrazole skeleton. Keywords: PhICl2; pyrazoles; selenocyanation

• ][44][45]. However, the electrophilic thiocyanation of biologically important pyrazoles has been less explored [46][47][48]. Among them, the majority of the reported methods proceed through a radical pathway, with the SCN radical generated by the reaction of the thiocyanate source with a corresponding

• presented a method for the C–H thiocyanation of pyrazoles by using a sustainable catalyst of graphite-phase carbon nitride (g-C3N4) under visible light irradiation (Scheme 1c) [2]. Furthermore, Yao harnessed an electrochemical approach to form the electrophilic SCN+ intermediate, which reacted with

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• hypervalent iodine(III) reagents has been developed [12][13][14][15][16][17] (Figure 1), including the well-known Zhdankin reagents [13] and Togni reagents [14]. These reagents are popularly used as electrophilic group transfer reagents [18][19] in a variety of reactions, such as C–H functionalization [20][21

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• carbon atom of isocyanide has both a lone electron pair and empty orbitals, so it has outstanding electrophilic and nucleophilic reactivity. At the same time, isocyanide also has good coordination ability to coordinate with metals to form diverse metal complexes [1][2][3]. Therefore, isocyanides have

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• -hydrazino form [17][24][25], we conceived the idea of reversing the reactivity of 4a–r in the six-membered cyclization process (N- vs O-annulation) through the generation of an electrophilic oxocarbenium [26][27] cation intermediate from the acetal residue at N-3 of the (thio)hydantoin core. To pursue our

• and very practical synthetic intermediates commonly employed for the in situ generation of highly electrophilic iminium ions [38][39][40][41]. Conclusion In summary, we planned the synthesis of decorated imidazo skeletons accessible through a judicious choice of the starting components of a 3-CR

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• electrophilic alkene and forms the target product. N-Alkoxyphthalimides: In 2019, Tang and co-workers [53] utilized N-alkoxyphthalimides for the generation of alkyl radicals by reacting photogenerated alkoxyl radicals with P(OMe)3 (Scheme 17). This strategy provided the alkylation of allyl and alkenyl sulfones

• bond homolysis. In 2022, MacMillan and co-workers [56] outlined a comprehensive and direct deoxygenative hydroalkylation method for various types of electrophilic olefins (Scheme 20). This method involved primary, secondary, and tertiary alcohols and was facilitated by the use of a newly developed NHC

• β-scission, NHC 72 was found to be most effective. Unstrained secondary alcohols were efficiently activated with the help of NHC 65. Deoxygenation of sterically congested alcohols, which has been a longstanding challenge in organic synthesis, was achieved by using a more electrophilic alcohol

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• intrinsic properties, which result in protonation-initiated cyclization, Cope rearrangement, and atropisomerism. Finally, we exploited the reactivity of the trans-eunicellane skeleton to generate a series of 6/6/6 gersemiane-type diterpenes via electrophilic cyclization. Keywords: atropisomer; Cope

• rearrangement; DFT calculations; diterpene; electrophilic cyclization; eunicellane; Introduction The eunicellane diterpenoids are a family of nearly 400 natural products that present a conserved 6/10-bicyclic hydrocarbon framework [1][2][3]. Mostly known from soft corals [2], but with a growing number of

• recent discovery of the aridacins, which transforms a 2E-cis-eunicellane into a 6/7/5-tricyclic diterpene via a cytochrome P450 [12]. Coincidentally, these reactive skeletons also provide chemists the ability to access synthetically challenging scaffolds with simple electrophilic cyclizations. With

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• enabling the activation of small yet highly relevant organic substrates. For example, Huber and co-authors recently designed a Te-based catalyst in an indole Michael addition reaction [1][2][3][4][5]. Pale and Mamane utilized another Te-based catalyst in an electrophilic bromine-mediated cyclization

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• , and methyl anthranilate, with selenium dioxide in acetonitrile. A systematic analysis of the reaction products with the help of 77Se NMR and single-crystal X-ray crystallography revealed that the reaction progress follows three major reaction pathways, electrophilic selenation, oxidative

• using SeO2 as an electrophile source in aromatic electrophilic substitution reactions. Keywords: arylamines; electrophilic substitution; oxamides: polymerization; selenium dioxide; Introduction Organoselenium compounds have received considerable attention due to interesting medicinal properties, such

• interest [12][13]. The various approaches used for selenation of aromatic compounds include directed lithiation [14][15], copper-catalyzed selenation [16][17][18], and aromatic nucleophilic substitution reactions [19][20][21][22]. Electrophilic selenium reagents (e.g., phenylselenenyl bromide) have often

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• (LUMOs). In addition, silylenes are characterized by both nucleophilic properties based on the high HOMO levels, and electrophilic properties because of the low LUMO levels [50][51]. The Mulliken charge densities of 2s are also shown in Figure S2 (Supporting Information File 1), which shows that the

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• heterocyclization reactions by exploiting the electrophilic character of Pd(II) species. Starting from substrates bearing a triple bond and a nucleophile in the appropriate position, a versatile process of heterocyclization can be initiated, resulting in indole derivatives with important properties. Gabriele et al

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• products) were found to be somehow unstable when concentrated to dryness during work-up. We hypothesize that a possible cause of such instability might consist in the formation of a highly electrophilic iminium ion upon protonation of the hemiaminal ether by silica or glassware acidity and further

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• from a self-propagating process initiated by addition of an adventitious nucleophile to the electrophilic thioester. This results in elimination of a (trifluoromethyl)thiolate (−SCF3) anion (C, Scheme 4), which can subsequently undergo β-fluoride elimination, releasing a fluoride anion. Addition of F

• highly electrophilic compound can react with the carboxylic acid in the presence of DIPEA via addition/elimination affording a thioic anhydride species E and a fluoride ion [9]. Addition of F− to the carboxyl carbon followed by fluoride elimination from the resulting thiocarboxylate would provide acyl

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• functional groups adjacent to them, due to withdrawing effects. Chlorine has a stronger electron-withdrawing effect than bromine, so the electrophilic character of the 6-position should be higher than that of the 5-position. However, it is unlikely to be the only reason for the formation of just one

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• was developed by Anderson and co-workers and was shown to be the more versatile than initiator-free activation. Both initiator-free and Et3B-initiated reactions only tolerated electrophilic radicals (to 134a and 134e), while photoredox catalysis also tolerated electron-rich radicals (to 134b). The

• -workers, and was accessed over 8 steps from diene 161 (Scheme 17A) [51]. Diels–Alder reaction of diene 161 and di-tert-butyl azodicarboxylate (160) followed by palladium-assisted elimination of acetic acid gave diene 162. A sequence of 4π-electrocyclisation and electrophilic transcarbamation (to 163

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• . Keywords: annulation; arylocyclization; 3,4-benzocoumarin; diaryliodonium salts; naphthol; Introduction Diaryliodonium salts as electrophilic reagents have attracted significant attention in the field of organic synthesis owing to their efficiency and selectivity [1][2][3][4][5][6][7]. Particularly, they

• , expanding the benzocoumarin family (Scheme 1b) [14]. Recently, ortho-functionalized diaryliodonium salts, due to their coordinating and electrophilic effects, have exhibited unique reactivity and chemoselectivity [15]. As such, a wide range of functional groups including the trimethylsilyl group, boronic

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 glycosidic bond using an organometallic purine or pyrimidine derivative and an electrophilic furanose derivative [23][25]. This process can result in anomeric mixtures, so 5 has potential applications in targeted synthesis, as the configuration of the pseudo-anomeric centre matches the common

• 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

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• electrophilic trapping of onium ylides generated from metal carbenes with nucleophiles, providing an ingenious difunctionalization strategy for diazo compounds to access structurally complex and diverse molecules (Scheme 1b, top) [28][29]. In recent years, radical-mediated MCRs with diazo compounds have become

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• ), a supporting ligand that would be predicted to create more electrophilic gold due to its high π-acceptor properties, major decomposition was observed for the slower substrates (1b and 1c) and the fast urea (1a), indicating catalysts that are much more prone to decomposition, and preventing any

• electrophilic enough to activate alkenes toward the attack of pyrroles [34][35]. Gold-catalyzed reactions are known to be sensitive to subtle anion and media effects [48], and within the binary of rate determining π-activation versus protodeauration, trends do not always provide obvious conclusions. The unique

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• generate a fluoride ion that facilitates limiting enolization processes, and an electrophilic N–F fluorinating agent that is reactive towards neutral enol species. Keywords: difluorination; difluoromethylene; direct fluorination; electrophilic fluorination; organofluorine; Introduction Fluorine is

• fluorodesulfurizations of carbonyl derivatives using a combination of sources of halonium and fluoride ions such as 1,3-dibromo-5,5-dimethylhydantoin (DBH) and tetrabutylammonium dihydrogen trifluoride have been achieved [9][10][11]. The transformation of methylene to difluoromethylene using electrophilic fluorinating

• agents offers an alternative fluorination route, for example, the reactions of MeCN solutions of 1,3-diketones with electrophilic fluorinating agents such as Selectfluor eventually give the corresponding 2,2-difluoro-1,3-diketone derivatives [12]. Monofluorination of the 1,3-diketone substrates is rapid

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• pharmaceutical and biological activities. Among indole derivatives, bis(indolyl)methanes (BIMs) are profoundly interesting, due to their wide range of pharmaceutical properties. The most common approach involves the electrophilic substitution of various aldehydes and ketones by indoles, utilizing either protic

• . The difference between the two mechanistic pathways is the nature of activation of the carbonyl group. Protic acids induce the protonation of the carbonyl group of the aldehyde or ketone, enhancing its electrophilic character. Whereas, Lewis acid catalysts bind to the heteroatom of the carbonyl group

• research group explored the activity of cadmium sulfide (CdS) nanotubes as heterogeneous nanocatalysts for the electrophilic condensation between aldehydes and indoles [106]. The nanorods were obtained with a solvothermal technique, where thiourea and cadmium nitrate were mixed in ethylenediamine for 10

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• electrophilic center C(1) of 1 is much lower. It comes, therefore, with no surprise that the interaction of arylamines and the 5-hydroxy and 5-acetoxy derivatives of 3H-phenoxazin-3-one is directed toward the C(2) reaction center to yield 2-amino-3H-phenoxazin-3-ones as the final products under aerobic

• formation [6]. In turn, without an acidic catalyst, it is driven by the distribution of the electron density (Figure 1), such that the nucleophilic attack occurs at the most electrophilic C(2) center. With this in mind, we presented a convenient procedure for the SNH reaction of aromatic amines with