Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• -osaka, Osaka 577-0056, Japan 10.3762/bjoc.22.61 Abstract E-Selective bromination for diphenylacetylene was established by using the combination of NBS and FeBr3 in CH2Cl2. In addition, easy purification and separation from the crude product were found. When the crude product was treated with heptane

• , the E isomer could be recovered as a solid material by utilizing the difference in solubility. On the other hand, the Z isomer could be removed by filtration while remaining in solution. Keywords: bromination; diarylacetylenes; green chemistry; purification and separation; stereoselective reaction

• reported studies suggest that it is surprisingly difficult to obtain the E isomer selectively (Scheme 1). For selected examples, Espenson and co-workers reported in 1999 that E-selective bromination of diphenylacetylene took place by using H2O2, NaBr, and AcOH in the presence of MTO (methyltrioxorhenium

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• ]pyridine-2-carbaldehydes has been developed that proceeds via the 2-methyl esters resulting from the Groebke–Blackburn–Bienaymé reaction, followed by reduction to the corresponding alcohols, bromination and then mild Kornblum oxidation. Other typical oxidation reagents such as PCC, IBX and laccase gave

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• purity (>95%). Semisynthetic analogues 3−5 are known compounds [25][26]. However, some of these compounds have not been fully characterized. Regarding compound 5, this molecule had previously been reported as an intermediate in the total synthesis of racemic pinoresinol [25]. Through a bromination

• /z: [M + Na]+ 395. Bromination of (+)-pinoresinol (2) (+)-Pinoresinol (2, 10.0 mg, 0.028 mmol) was dissolved in CH2Cl2 (600 μL) before NBS (9.9 mg, 0.056 mmol, 2 equiv) was added. The reaction mixture was stirred for 1 h at room temperature and dried before being preadsorbed to C18-bonded silica (≈1

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• photoredox activation, followed by anion-binding-catalysed functionalisation to form β-amino esters. Here, the reacting atom is the one with the lowest hydricity and BDE. Compounds 8–10 Schmidt et al. [44] reported the visible light-catalysed bromination of compound 8, Kamon et al. [45] reported the light

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall

• give protected acetophenone 1 in an excellent yield of 78%. Next, the reaction conditions for the following α-bromination of acetophenone 1 to intermediate 2 were screened (Table S1, Supporting Information File 1). The treatment of compound 1 with CuBr2 in EtOAc at either room temperature or 60 °C

• (Supporting Information File 1, Table S1, entries 3–5, and 7). When NaHCO3 was used as an additive to neutralize HBr in the reaction mixture that was responsible for the cleavage of MOM, bromination with PTT was also unsuccessful in that the bromination occurred at the benzene ring and MOM was partially

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• -nitrobenzaldehyde, which is accomplished by benzylic bromination followed by a Kornblum oxidation. This gentle oxidation avoids the need for chromium trioxide-mediated or nitrone-based methods. While other published syntheses of 6,6’-dibromoindigo have resulted in higher overall yields, our approach offers the

• nitration of p-toluidine (2), followed by a Sandmeyer bromination [5][6][7][8][9]. While such chemistry is effective in smoothly generating 3 in good yield, this process requires the production of and use of a potentially explosive aryldiazonium intermediate [10]. Oxidation of the methyl group in 3 yields 4

• intermediate, synthetic challenges remain. Specifically, the synthesis of 3 is challenging, often requiring Sandmeyer bromination to set the regiochemistry of the bromine [5][6][7][8][9]. Additionally, the oxidation of 3 to 4 often utilizes toxic chromium(VI) or a lengthy process [8][9][11][12][13][14][15][16

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• excellent yield, the structure being confirmed using single crystal X-ray analysis (CCDC 2495984). Bromination afforded a mixture of symmetric cycloheptatriene 4b and norcaradiene 6b, while intermediate cycloheptatriene 5b was not even observed. Iodination gave exclusively norcaradiene 6c. Previously

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• followed by reaction with CH(OMe)3 afforded acetal 17, which was then subjected to a CH2Cl2 solution of TMSOTf and iPr2NEt. A mixture of enol methyl ethers 18 were thus produced by an elimination reaction. Eventually, a site-selective bromination of the double bond over the electron-rich benzene rings with

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

• monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• compound [29] and can be prepared from readily available m-anisyl alcohol by using iodination and bromination reactions (see Supporting Information File 1 for the details). Subsequently, an SN2 reaction between 2 and tert-butyl cyclopropanecarboxylate (3) in the presence of LDA delivered product 4 in 87

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 amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• radicals, while halogenation was promoted by the introduced halogen atom [26]. In 2014, Alexanian’s group reported a site-selective aliphatic C–H bromination utilizing modified HRP as both the bromination reagent and HAT reagent (Scheme 11) [25]. Initiated by visible light, HRP-10 underwent homolytic

• that regenerated amidyl radical 45. This system effectively examined the site selectivity of aliphatic C–H bromination, yielding products 80–82, and 83 with 54% to 63% yields at selective positions. This bromination system provided a mild reaction environment suitable for aliphatic C–H bonds. In 2016

• carbanion, which undergoes either solvent-mediated protonation or direct proton transfer from the acridiniumamide, ultimately delivering product 89 while regenerating the zwitterionic HRP-12 catalyst. This catalytic platform demonstrated exceptional site selectivity in aliphatic C–H bromination under

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• does not exhibit biradical character. Instead, heptagons and pentagons are primarily non-aromatic, with a localized double C=C bond in the seven-membered ring, giving compound 29 predominantly benzenoid properties. Interestingly, PAH 29 undergoes single or double bromination with NBS in a mixture of

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

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

• reaction temperature and time. Indeed, bromination of [3.3.3] and [4.3.3] was reported as three/six- and two-fold reactions, respectively [45][47][53]. If the amount of bromine was limited, the resulting nearly random mixtures of brominated compounds would be practically impossible to separate by

• % owing to competing decomposition. As a substrate, a mixture obtained by monobromination of [4.3.3] could be used, giving difunctional building block [4.3.3]_Br_CHO in 39% yield (Table 1, entry 7). The reaction was highly successful because the bromination gave nearly random 1:2:1 mixtures of [4.3.3

• on a naphthalene ring. It was reported that bromination proceeded in three- or six-fold manners for a [3.3.3]propellane [45][47][48][49][50][51][52], and in two-fold one for a [4.3.3]propellane [53][54]. Nitration of the [3.3.3]propellane also yielded an exclusive six-fold product [46]. The current

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• yield of 88%. (R)-Methyl 6-oxopipecolate (7) was converted under Vilsmeier–Haack conditions [35][40][41] to undergo N-formylation and concomitant enol bromination to give product 2 (Scheme 2). Due to slow degradation of the bromide 2, the subsequent cross-coupling reaction was conducted immediately

• for (2R,6S)-13 and b) for the chair conformations of (2R,6R)-13. ᴅ-2-Aminoadipic acid (1) can be used to generate C6 aryl and alkynyl-modified pipecolic acid derivatives. Methyl ester formation, followed by cyclization, N-formylation, as well as bromination under Vilsmeier–Haack conditions. Suzuki

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• pyrrolopyrimidine derivatives. The envisioned methodology combines a Sonogashira–Hagihara reaction and a one-pot process comprising a Buchwald–Hartwig coupling reaction followed by a hydroamination [23][24]. Results and Discussion The bromination of 6-chloro-1,3-dimethyluracil (1) afforded, following a known

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

• divergent total synthesis of several Cephalotaxus alkaloids. The α-hydroxylation of cyclopentanone, followed by amide reduction and methanol elimination in one-pot, produced (−)-cephalotaxine in 9 steps. Alternatively, Riley SeO2 oxidation of 31, benzylic bromination/hydrolyzation, facial selective ketone

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

• investigated in the future. In view of future applications in quantum technology, further effort should be directed at ways to increase coherence time, as was done in the study of increasing bromination of trityl radicals [55]. Moreover, such systems would also benefit from strategies to increase their

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• mild reduction with methanolic sodium borohydride. Upon purification by reversed-phase chromatography using aqueous hydrobromic acid as eluent (0.5% in H2O), a considerable fraction of the alcohols was already converted to the desired bromides 4c,d. Only in the case of 4b, no deoxygenative bromination

• was observed, and the alcohol intermediate was isolated in pure form. In both cases, quantitative bromination was achieved by heating the compounds in concentrated aqueous hydrobromic acid, which after evaporation afforded the pure compounds 4b–d. To generate iodide 4e, alcohol 11 was isolated and

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

• cyanoacetic ester and acetylacetone. The configuration of the products 4 and 5 was established by bromination of a small amount of these isomeric compounds in CDCl3 (Scheme 6) and subsequent analysis of the mixture by 1H NMR spectroscopy. For the stereoisomers 4, the main product was lactone 22, identified by

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• , Huang, and Mei et al. explored Cu-catalyzed electrochemical C(sp2)–H bromination of 8-aminoquinoline amide at the C5 site of quinoline using NH4Br as a brominating reagent under anoxic oxidation conditions (Figure 13) [64]. This catalytic reaction has a broad substrate scope, and further investigation

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• -membered ring to an eight-membered ring [2]. Results and Discussion As shown in Scheme 1a, the synthesis of trione 1 started from the bromination of 4-bromo-2,3:6,7-dibenzotropone (4) [24], giving tribromide 5 in a yield of 64%. The subsequent elimination reaction of 5 with KOH afforded dibromide 6 in a