Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• from diisopropyl H-phosphonate (2a) was confirmed by HRMS analysis of the crude reaction mixture. Finally, vinyl azide 4a and silyl enol ether 4b were introduced into standard reaction conditions (Scheme 4, reaction 3). However, no phosphorylation product 3a was observed. On the basis of the obtained

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• led to recovery of starting material or a complicated mixture probably owing to the modestly electron-rich and sterically demanding naphthalene α-positions (Table S202, entries 1–3, Supporting Information File 1). By contrast, a combination of dichloromethyl methyl ether and TiCl4 (Rieche reaction

• [3.3.3], diformylated product [3.3.3]_2CHO was obtained in 5.1% yield. In expectation of successful multifold formylation, the equivalents of dichloromethyl methyl ether and TiCl4 were doubled (Table 1, entry 4). The yield of [3.3.3]_2CHO modestly increased to 25% with a slight decrease in the yield of

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• activation [34]. Overview of the predictive workflow: For the shown substrate on the left, three unique activation sites are possible (labelled “Ha−c” with two directing groups, a pyridine (blue) and an oxime-ether (red) group. The latter has two potentially directing atoms, nitrogen and oxygen. The

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• reacted with deprotonated diethyl malonate to obtain compounds 36 and ent-36 in 95 and 92% yield, respectively, over two steps from 34 and ent-34. The diols 28 (85%) and ent-28 (90%) were isolated after reduction of their parent malonates 36 and ent-36 using LiAlH4 in ether. Following several experiments

• LiAlH4 in ether to form alcohol 40 (89%) (Scheme 3). The primary alcohol 40 was then converted to its iodide derivative 42 (89%), from which single crystals were obtained, and its structure was determined unequivocally by XRD crystallography. Iodide 42 was then reacted with sodium phenylsulfinate in DMF

• % yield over three steps. This compound was isolated in its pure form as a white solid after recrystallization from ethanol, confirmed by HPLC and NMR. In parallel, the primary alcohol group of ent-38 was protected as a TBDMS ether, and the acetate group was converted to a tosyl ester by hydrolyzing the

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• , led to the quick formation of co-precipitates when added to aqueous solutions of β-CD and KAuBr4 (both at 5 mM): dibutyl carbitol, isopropyl ether, chloroform, dichloromethane, hexane, benzene, and toluene [51]. The most effective one was dibutyl carbitol (DBC), which caused 99.7% precipitation when

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• further understand the complexation with metal cations, separate co-crystals of HIM 1 with LiBArF20 and NaBArF24 were obtained by vapor diffusion of diethyl ether into acetone. The details of the co-crystallization experiment are provided in the crystallographic information section of Supporting

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• . Petroleum ether (PE, 60–90 °C fraction) and ethyl acetate (EA) were used as eluent. Reactions were monitored by thin-layer chromatography (TLC) on GF254 silica gel plates (0.2 mm) from Anhui Liangchen Silicon Material Co., Ltd. The plates were visualized by UV light. 1H NMR (400 MHz) and 13C NMR (101 MHz

• , dried over sodium sulfate, and freshly distilled prior to use. All solid aldehydes were used after recrystallization from petroleum ether (PE, 60–90 °C fraction) or a mixture of ethanol and water. All dialkyl 3-aryl-1-sulfonylaziridine-2,2-dicarboxylates 1 were synthesized by previously reported

• with a syringe and the mixture was stirred at 55 °C for 24 h. After gradually cooling to room temperature and removal of the solvent under reduced pressure, the crude residue was purified by basic aluminum oxide column chromatography with petroleum ether/ethyl acetate 1:10 to 3:7 (v/v) as eluent to

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• formation of an active α-ketenyl phosphorus ylide 345 (Scheme 77A) [130]. Similarly, Lin and co-workers (2024) employed PPh3 to selectively catalyze the esterification reaction of cyclopropenone 309 and amides to give the corresponding esters 346–348 containing an oxime ether in good yields (Scheme 77B

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• cyclopentane ring, dihydroxylation, and oxidation of the diol to a diketone, produced intermediate 25 in its enol form. From this common intermediate, regioselective etherification at the less hindered position formed an enol ether. Final reduction of both the amide and the ketone using alane completed the

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

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• .) of 24 led only to epimerization at C10 or slow decomposition of the starting material (see Supporting Information File 1, Table S1). Pleasingly, treating 24 with HMDS and TMSI regioselectively generated the expected TMS enol ether [46], which underwent a Li/Si exchange in the presence of MeLi

• H2O under neutral conditions merely resulted in decomposition (Table 1, entry 10). To our delight, photoirradiation of the corresponding methyl ether 31 at 254 nm in the presence of AcOH at 20 °C led to a smooth cyclization, followed by spontaneous elimination, which produced the desired 10 as the

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• target ultracyclic hosts. The synthesized ultracycles were fully characterized by spectrometric and elemental analysis (Scheme 1 and Schemes S1‒S3 in Supporting Information File 1). Single crystals of B4aH were obtained by slow vapor diffusion of ethyl ether into an acetonitrile/chloroform 1:1 (v/v

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• binding Na+ and K+ by oligourea foldamers and macrocycles [37][38][39]. However, in the solid−liquid extraction of Li2SO4 in DMSO, addition of crown ether did not help to increase the extraction efficiency. This is because ion-dipole interactions are negligible in high polar solvent, and Li+ binding is

• to be slightly upfield-shifted in comparison to that of the free crown ether, indicating Cs+ binding, consistent with their extraction efficiency. The relatively upfield shifted chemical shift for the Cs3PO4 complex may indicate strong cooperative interaction upon solid–liquid extraction. To

• understand cooperative interactions between complexed ions, we tried to grow the crystal structure of studied salts. Fortunately, single crystals of Cs2CO3 and Cs3PO4 complexes were obtained by slow vapor diffusion from acetonitrile and diethyl ether. Notably, clearly stronger ion-dipole interactions of

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• efficiently constructed α-all-carbon quaternary centers on β,γ-unsaturated nitriles with excellent >98% regioselectivity and >98% (E)-selectivity. 1,1-Disubstituted allenes bearing silyl ether- and benzyl ether-tethered propyl groups were successfully converted into the desired nitriles 3a–c in yields ranging

• regioselectivity (>98%). Functional groups such as silyl ether, benzyl ether, and chloro moieties on allenes 4d–f were well tolerated under the reaction conditions, producing nitrile-substituted tertiary carbon products 5d–f in yields ranging from 73% to 85%. Moreover, aryl-substituted allene 4g was efficiently

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• prominent Hayashi–Jørgensen catalyst. This prolinol silyl ether was independently discovered by the respective Hayashi and Jørgensen research teams in 2005 [13][14]. Interestingly, the use of prolinol alkyl ethers for asymmetric Michael additions, although at the time added in a stoichiometric manner, has

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• was impractical for the HBC derivative with a C4-handle (N-(4-bromobutyl)-HBC) due to intramolecular cyclization with the amine. To prevent intramolecular cyclization, we considered the 4-bromobutyl HBC ether 11 as a potential candidate with a 4-atom spacer. Accordingly, 4-hydroxybenzaldehyde was

• observed for the HBC ether 11 (C4 homolog) and the bromoethoxyethyl HBC 9 (“C5” homolog). No reaction was observed for the C2 homolog 7 (Figure 2). Notably, the reaction yields for all derivatives increased when the DMSO content of the reaction mixture was increased from 5 to 15%. (DMSO was initially used

• provide fluorophore 19. Subsequent palladium-catalyzed cross-coupling with tributyl(vinyl)tin resulted in the installation of the vinyl group (compound 20). Finally, cleavage of the silyl ether gave the free alcohol 21, which was converted into the corresponding mesyloxypropyl HBC ligand 22. 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

• macrocycle [74][75]. 2 Ethers We now turn our attention from alkanes to what is arguably the simplest heteroatom-containing functional group: the ether. The presence of oxygen within a carbon chain offers several new opportunities for engagement by an introduced fluorine atom. First, we will consider what

• ) bond, such that the endo orientation of the C–F bond (as depicted in I, Figure 6) is lower in energy than the exo conformer (not shown). This is an example of the anomeric effect [77]. The anomeric effect can be visualised perhaps most clearly when the ether moiety is embedded within a small ring [78

• also seen when Ar–O–CF2- is a linker moiety. For example, consider compound 47 (Figure 6), which is a fluorinated analogue of the antipsychotic drug, aripiprazole (46). The presence of the fluorine atoms in 47 causes a change in the conformation of the aryl ether moiety from planar in 46 [83] to

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• precipitated product was filtered, washed with H2O (20 mL), and dried in vacuo at 60 °C. The crude material was purified by flash column chromatography (SiO2, 10 → 100% EtOAc in diethyl ether) to yield 7 as a red solid (10.7 g, 12.9 mmol, 78%, 99% purity determined by analytical HPLC). 1H NMR (600 MHz, CDCl3

• , H2O (50 mL) was added, and the mixture was treated with aq HCl (6 M) to pH 2. The resulting solution was extracted with EtOAc (4 × 50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (SiO2, 20 → 100% EtOAc in diethyl ether) to

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

• otherwise predominant β-F elimination from the α-CF3-alkylcopper intermediate 39. Detailed kinetic studies confirmed the effect of the crown ether. When KOPiv was employed alone, the initial rate of defluorination increased by 1.57-fold, whereas the addition of 18-crown-6 reduced this acceleration to 1.22

• -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

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• ] and has been used in syntheses of natural products containing aryl quaternary carbon centers [9][10]. Unlike the intramolecular alkylation strategy of a phenol derivative, which can only be applied in basic dearomatization reactions, our approach using an α-iodophenol ether as precursor of the

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• binding of tryptophan is therefore important for diagnostic and medicinal applications. Recently, we reported a glucose naphtho crown ether which is a chemoselective receptor for the esters of aromatic amino acids, in particular tryptophan, in water. Herein, we demonstrate that the same compound also

• aqueous media is limited (Figure 1a–c) [13][14][15][16][17][18]. In particular, receptors which bind tryptophan residues in peptides are rare [19][20]. Recently, we developed a glucose-based naphtho crown ether 1 (Figure 1d) which binds amino acid methyl esters with aromatic side chains chemoselectively

• in water [21]. Crown ether 1 is particularly suited for the sensing of Trp methyl ester, which it binds with a higher affinity than the Phe and Tyr esters. Additionally, the binding of Trp-OMe results in a highly efficient fluorescence quenching of the naphthalene unit in the receptor. Herein, we

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

• , dried over 4 Å molecular sieves); quinine hemisulfate salt monohydrate (Fluka); sulfuric acid (EMD Chemicals); diethyl ether anhydrous (EMD Chemicals, ACS grade); chloroform-d (CDCl3, Cambridge Isotope Labs, 99.8%); hexafluorobenzene (C6F6, Oakwood Products); deionized distilled water (purified with a

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• the C-2 position also contribute to the concept of ‘armed–disarmed’ glycosylation wherein C-2 ether-protected ‘armed’ thioglycosides were selectively activated over C-2 ester-protected ‘disarmed’ thioglycosides owing to the electron-withdrawing attribute of the ester carbonyl functionality [93

• intermediates [144]. However, C-2 phthalimidoxy-protected trichloroacetimidate glycosyl donors gave higher 1,2-trans selectivity in comparison to C-2 phthalimidoxy-protected N-phenyl 2,2,2-trifluoroacetimidate glycosyl donors. Ether-type participating protecting groups: In the absence of neighbouring acyl-type

• of a mixture of 1,2-cis and 1,2-trans glycosides. In this respect ether-type non-participating protecting groups like benzyl (OBn), p-methoxybenzyl (OMBn), and allyl (OAll) are implemented as the temporary protection in the C-2 position in order to obtain 1,2-cis glycoside products. Moreover, the

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• alcohol 2. Its 1H NMR spectrum contained a triplet with a coupling constant of 5.1 Hz at 5.52 ppm and a doublet at 4.30 ppm. In methanol, ethanol and petroleum ether, with an increasing reaction time, a significant amount of product 3 was observed in the 1H NMR spectra of the mixtures, as identified by