Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• ]. When a para-fluorine substituent is present on the naphthalene ring of the substrate, the reaction proceeds with a yield of up to 90% and an enantioselectivity reaching 92% ee. The methodology demonstrates a broad substrate scope, accommodating various polycyclic naphthalene isoquinolines as well as

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• Baeyer–Villiger oxidation affording the fluorinated, chlorinated, and brominated dideoxyribonolactones. Keywords: butyrolactone; cyrene; fluorine; halogenation; levoglucosenone; Introduction The γ-butyrolactone ring is a privileged scaffold found in natural products and can be used as a valuable

• intermediate in synthesis [1][2]. Several nucleoside analogue drugs are prepared using γ-butyrolactones, that when reduced give pentose sugars that can be used as glycosyl donors [3][4]. A number of these clinically used drugs contain fluorine as a hydroxy bioisostere at C2, most notably gemcitabine (1) and

• electrophilic fluorine in the best case gave 15% conversion for NFSI and less than 8% isolated yield of 7c for SF. The major product in these reactions was 5, due to a β-elimination of the amine. In comparison, the reaction of 15 with NBS afforded 7b in an unoptimized yield of 48% after hydrolysis, which

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• polarity, with these effects varying based on the amount, position, and orientation of the fluorine substituents [7][8]. Mondal and colleagues have extensively reviewed additional properties of fluorinated cyclopropanes, including the conformational behavior of substituents attached to a fluorinated

• kcal mol−1 more stable than two isolated molecules – and an atoms in molecules (AIM) analysis reveals a bond path between hydrogen and fluorine atoms, with an electron density of 0.0048 at the bond critical point (Figure 2). Based on AIM charges (qH = +0.0851 and qF = −0.6003) and a H···F distance of

• these complexes, the cation coordinates with the fluorine atoms, while the anion interacts with the positively charged hydrogen atoms. The complexation is thermodynamically favorable when compared to the isolated species (ions and 1.2.3-c.c.), as indicated by the ΔH0 of formation: −32.5 kcal mol−1 for

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• surface at ambient conditions. The fluorine substitution is chosen in FNAAP for its better photoisomerization efficiency (in solution as well as in solid state) and higher molecular stability [29]. Possible photoisomers of FNAAP, EEE, EEZ, EZZ and ZZZ are shown in Figure 1. FNAAP molecules assemble into

• is to be noted that the fluorine atoms are oriented toward the aromatic and aliphatic hydrogen and the carbonyl group to aromatic hydrogen. This suggests possible directional non-bonding interactions between the molecules. For molecules with 3-fold symmetry, the 3-fold orientation within the assembly

• the vectors. Black arrows indicate the compact lattice directions of graphite. Magenta dashed lines depict possible non-bonding interactions between carbonyl groups and aromatic hydrogen atoms. Blue dashed lines depict the same between fluorine and aromatic/methyl hydrogen atoms. (a) Current versus

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• group surrounded by fluorine atoms, which could spontaneously deprotonate in polar solvents, while the tautomeric OH/NH group is always a part of strong intramolecular hydrogen bonding and the possibility for deprotonation is low. The deprotonation of the phenyl OH group is also supposed by the

• the diazonium salts are made alkaline the para-fluorine atom is so readily replaced by a hydroxy group, and that the 4-hydroxy-2,3,5,6-tetrafluorobenzene cation is the entity formed first [90][91]. A 50 mL round-bottomed flask equipped with a mini magnet was charged with pentafluoroaniline (0.64 g

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• compounds is provided by the variation of substituents in positions 2–5 of the 1,2-thiazole ring. Thus, arylsulfonyl groups containing a methyl, fluorine, chlorine, or nitro group at the aryl moiety, or a mesyl substituent were introduced into position 2 of the thiazole ring and various aryls, quinolinyl

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• difluoroethylsulfinate (DFES-Na) to generate difluoroethyl radicals via anodic single-electron oxidation (Scheme 23) [14]. The method was evaluated with various N-arylacrylamides, revealing that substrates with different substituents, including fluorine, chlorine, bromine, and iodine, participated well in the reaction

• –c) and electron-withdrawing (e.g., fluorine, chlorine, ester groups) (78d–f) substituents on bromodifluoroacetamides were well tolerated, yielding high reaction efficiency. Interestingly, the reaction was less sensitive to electronic effects on the aromatic ring, as yields remained high regardless

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• low ϕ (see Figure 2a) [50][51]. Perfluorinated triphenylmethyl radicals have been reported as well; however, neither UV–vis nor photoluminescence data are available [54]. Mixed perhalogenated triphenylmethyl radicals with fluorine, chlorine, and bromine substituents have been synthesized in an attempt

• , these molecules display greatly enhanced photostability compared to PTM and TTM. The ortho-positions on the pyridyl ring have been substituted with fluorine, chlorine, and bromine moieties, and it was found that the change in substitution affects the emission color from yellow in case of fluorine, to

• orange for chlorine, and to red for bromine [6][57]. This shift can be explained by the decreasing electronegativity of the halide substituents. The more electronegative fluorine will reduce the HDMO energy more strongly than the bromine, while the SOMO remains energetically almost unaffected, explaining

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• imides and TMS-alkynes, enabling the rapid construction of S(VI)–C(sp2) or S(VI)–C(sp) bonds efficiently (Scheme 24) [55]. This linkage utilizes the high bond dissociation energy (BDE = 135 kcal/mol) of silicon–fluorine bonds, employing trifluoroborate as a fluorine transfer reagent to simultaneously

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• phosphoroselenoates were formed with moderate to high yields in the presence of electron-donating groups such as methyl (Me) and methoxy (OMe), as well as electron-withdrawing groups like fluorine (F), chlorine (Cl), bromine (Br), and nitro (NO2) at the 5-position of the phenyl ring in indole. Studies showed that

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• azobenzene derivative 9 [34] to furnish 10. This reaction had to be carried out at −78 °C in order to suppress nucleophilic substitution of the ortho-fluorine substituents in 9 by the thiol 8, a reaction that competes with the desired cross-coupling. For the second Buchwald–Hartwig–Migita cross-coupling, the

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• stereoelectronic effects such as hyperconjugation and electrostatic attraction/repulsion. These fluorine-derived conformational effects have been exploited to control the shapes, and thereby enhance the properties, of a wide variety of functional molecules including pharmaceutical agents, liquid crystals

• fluorine atoms into the structure. The C–F bond has certain fundamental characteristics that enable it to serve as an effective conformational tool (Figure 1) [2][3][4]. First, the C–F bond is quite short at only ≈1.35 Å (cf. ≈1.09 Å for C–H, or ≈1.43 Å for C–O). The short length of the C–F bond, and the

• compact size of the fluorine atom itself, means that fluorine can be incorporated into an organic molecule as a replacement for hydrogen without drastically altering the molecular volume. Second, the C–F bond is highly polarised. This means that any molecular conformation in which the C–F dipole is

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• phenacene molecules are quite robust against an oxidative environment even under photoillumination, they are considered to be promising platforms for constructing practical organic functional molecules. Recently, fluorinated PAHs attracted considerable attention because the introduction of fluorine atoms

• 18-crown-6 produced fluorine-containing diarylethene 8 as a mixture of E- and Z-isomers. Subsequently, the E/Z mixture of 8 was subjected to the Mallory photoreaction without separation. Thus, compound 8 was irradiated with fluorescent black-light lamps (300 nm, 6 × 16 W) in the presence of a

• -extension (ΔλABS = ca. 6 nm per increment of one benzene ring) and the spectral profiles resemble each other irrespective of the length of the phenacene π conjugation and the fluorine substitution. The results suggest that these factors could provide insignificant effects on the apparent electronic spectral

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• -fold. These observations supported the hypothesis that the crown ether effectively disrupts the interaction between the alkali metal cation and fluorine atom, thereby decreasing the rate of β-F elimination. This asymmetric copper-catalyzed protocol represents one of the rare examples that allows to

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• ] as electrophiles. It is noteworthy that the development of such vinylogous functionalizations of this nitrogen heterocycle with a fluorine-containing electrophile may be of interest to pharmaceutical and medicinal chemists. Results and Discussion 4-(Alkenyl)-5-aminopyrazoles 3 were selected as

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• observed for 9,10-ANTH(X)2 derivatives bearing fluorine-containing electron-withdrawing groups. For example, the Φf values increased from 0.28 for ANTH to 0.54 (X = F) to 0.68 (X = CF3) which is similar to that of X = C6F5 [32]. To our knowledge, 9,10-ANTH(BnF)2 has the second highest Φf value reported for

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• 1. If electron-withdrawing substituents are added in ortho-position of the additional phenyl ring (12 and 13) the half-life is not affected significantly as well. An increase of about 10% of the half-lives has been observed for the weak +M substituents bromine (10) and fluorine (11) or methyl groups

• the switching behavior while weak +M substituents like bromine and fluorine as well as electron-poor heteroaromatic systems lead to increased thermal half-lives. An amino-substituted derivative 21 was obtained via Buchwald–Hartwig coupling with Boc-carbamate and subsequent deprotection. Amino

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• instability, where the cleavage of the phthalimide and glutarimide rings comprises the major metabolic pathways [9][10]. Computational analysis confirms that C1, C3, C2’, and C4’ are the most electrophilic sites of thalidomide (Figure 4). As expected, introducing a fluorine atom to C4 activates it toward SNAr

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• good tolerance for both electron-withdrawing groups such as fluorine (–F), bromine (–Br), and chlorine (–Cl), as well as electron-donating substituents like methoxy (–OMe) and methyl (–Me), yielding the corresponding 6-membered tricyclic imidazoles in moderate to good yields (3b–h). Benzene rings

• aryldifluoromethylation/cyclization reaction (for details about optimization conditions, please see Supporting Information File 1). We were delighted to find that when 2-fluorophenylacetic acid was employed as the fluorine source, a wide range of benzimidazole substrates were also compatible with this reaction. For

• tricyclic and bicyclic imidazoles under additive-, base-, and metal catalyst-free conditions utilizing difluoroacetic acid and α,α-difluorobenzeneacetic acid as the readily available fluorine sources. The significant advantages of this approach, including its environmental friendliness and cost

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• (CF2H); fluorine; hydrogen bond donors; hydrogen bond strength; Introduction Hydrogen bonding interactions are ubiquitous non-covalent forces in chemistry and biology [1][2][3][4]. In canonical hydrogen bond (HB) donor–acceptor pairs, the donor typically comprises an electronegative heteroatom, such as

• Research Fellow supported by the ACS Division of Fluorine Chemistry. M.E.P. acknowledges support from the Office of Undergraduate Research and Innovation at the University of Rhode Island and the CAREERS Cyberteam Program funded by the National Science Foundation (Award No. 2018873). J.M.G. acknowledges

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• successfully synthesize a range of 2-arylbenzofurans with various substituents. The reaction, which proceeded under mild conditions, involved β-fluorine elimination from nickelacyclopropanes formed by the interaction of 2-fluorobenzofurans with zero-valent nickel species. This protocol facilitates orthogonal

• coupling reactions of aromatic C–F and C–Br bonds with arylboronic acids. Keywords: arylboronic acid; benzofuran; C–F bond activation; cross-coupling; nickel; Introduction The metal-catalyzed activation of aromatic carbon–fluorine (C–F) bonds is widely recognized as a challenging task in synthetic

• developed efficient metal-mediated methods for activating (i) vinylic [8][9][10][11][12][13] and (ii) allylic C–F bonds [14][15][16][17][18] using β-fluorine elimination under mild conditions. In these studies, (i) we discovered zirconium-mediated β-fluorine elimination from zirconacyclopropanes A, which

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• fluorescence emission spectroscopies reveal green photoluminescence with fluorescence quantum yields of up to 33% for the Fn derivatives. The J-aggregation for the inner fluorine-substituted dimers Gnm is energetically and stereoelectronically more favorable and G66 exhibits thin-film fluorescence with a large

• fluorine atoms, inserted in the aromatic rings, which considerably modifies the dipole moment of the corresponding fluorinated aromatic rings with respect to their hydrogenated homologs, thus influencing their behavior, binding affinities, and optoelectronic properties. These interactions already represent

• an effective tool for the design of liquid crystalline materials [3][4][5][6][7][8]. Rod-like liquid crystalline molecules with fluorine-substituted arenes are ubiquitous in the displays industry [12]. They are also gaining importance in the design of π-conjugated polycyclic aromatic discotic liquid

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• reactants. Finally, DFT calculations provided insights about the mechanism of this transformation, which strongly suggest that an SN2 reaction is operative. Keywords: alkylation; DFT calculations; fluorine chemistry; hypervalent iodine; sulfoxonium ylide; sulphur ylides; Introduction Introducing fluorine

• of compounds, increase their metabolic stability, and boost their lipophilicity [5][6][7]. Consequently, developing new synthetic techniques that incorporate fluorine and fluorinated groups represents a significant area of research in synthetic organic chemistry [8][9]. Among the various fluorine

• mesh) as a stationary phase (eluent n-hex/AcOEt 5:95%). Representative examples of fluorine containing, biologically active compounds. Possible mechanisms for the reaction of 1a and 2a leading to 3a (via B), proceeding via either halogen-bonded adducts and reductive elimination (path 1) or directly via

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• is known about its β-analog (Figure 3), although β-amino acids have been shown to strongly modulate the structural, metabolic, and biological characteristics of peptides [13]. Finally, it is well known that fluorine is a very useful tool in medicinal chemistry as the incorporation of fluorinated

• 19F,1H NOE experiments of compound 8f did not show any specific correlation between fluorine atoms and the protons of the amino acids (see Supporting Information File 1). Finally, the low chemical shifts of the amide and carbamate protons (6.4 ppm for NH of valine and 5.5 ppm for the NH of