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

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• product 24f. To show the applicability of this novel methodology, a gram-scale reaction was carried out obtaining comparable results as in a small scale. Besides, an α-bromination of the product 24f was performed obtaining 25 in 73% yield and complete diastereoselectivity (Scheme 9). In 2021, Zhao and co

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• into the polymer system, further modification and structural analyses were performed [48][74]. The axle end was easily modified by bromination of the benzene ring and successive transition metal–catalyzed cross-coupling reaction, such as Suzuki or Sonogashira coupling (Figure 10A). Furthermore, the

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• Information File 1) [75]. Different reagents for the bromination or chlorination were also evaluated (Table 1, entries 1–3) and NBS was the most efficient one (Table 1, entry 1). With the best reaction conditions in hand, the nature of the hydrazone part was first investigated (Scheme 2). Under standard

• conducted in the presence of 1a in a THF/MeCN mixture (1:1) [75], but no product was detected (Scheme 4D). Based on these experiments and literature data [66], a two-step one-pot process was suggested based on 1) the bromination of the hydrazone 1 followed by 2) the anion metathesis in the presence of

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• be developed by considering active structures. This was demonstrated by Crawford et al. [86] in their investigation of a peptide-catalysed atroposelective bromination (Figure 5). The authors found that the peptidic catalysts can broadly be defined in two categories of β-turns: a type I’ pre-helical

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• for our needs [52][53]. Benzylic bromination followed by nucleophilic substitution offers a general approach for the introduction of the nitrogen atom [54][55][56]. Consequently, the continuous flow Wohl–Ziegler bromination of 2b was attempted [57]. Even though we could observe excellent LCMS

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Avenida Francisco J. Múgica S/N 58030, Morelia, Michoacán, México 10.3762/bjoc.20.141 Abstract The reaction mechanism for the chlorination and bromination of 2-naphthol with PIDA or PIFA and AlX3 (X = Cl, Br), previously

• an equilibrium of Cl–I(Ph)–OTFA–AlCl3 and [Cl–I(Ph)][OTFA–AlCl3], rather than PhICl2 being the active species. On the other hand, bromination using PIDA and AlBr3 was more efficient, wherein the intermediate Br–I(Ph)–OAc–AlBr3 was formed as active brominating species. Similarly, PhIBr2 was higher in

• halogenation via PhIX2. Keywords: aromatic bromination; aromatic chlorination; density functional theory (DFT); hypervalent iodine; iodine(III); Introduction Hypervalent iodine(III) reagents have gained attention as strong oxidants with a low toxicity [1][2][3][4][5][6][7][8] and due to the ability to mimic

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• type haloalkenes. (b) Fate of unsymmetrical dialkyl ketones on direct bromination. (c) This work. Substrate scope. Unless otherwise stated 0.2 mmol of 1 was used and the isolated yields are given. Proposed catalytic cycle. Conditions screening (without oxidant)a. Conditions screening (with oxidant)a

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• -bromoaniline (1a) and ethyl trifluoroacetoacetate (2), adapting a known procedure from Schlosser and Marull (Scheme 1) [17]. The cyclization of 1a with 2a chemoselectively afforded 8-bromo-2-trifluoromethyl-4-quinolone (3) rather than 8-bromo-4-trifluoromethyl-2-quinolone. Bromination of 3 with phosphoryl

• bromination in position 3, followed by treatment of brominated intermediate 10 with phosphoryl bromide (Scheme 5) [34]. To our delight, the optimized conditions for the synthesis of alkynylated quinolines 6 could be applied also to the three-fold Sonogashira reaction of 11. However, the reaction time had to

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• be employed in two variants modulated by light irradiation. This external switch can be used to selectively trigger side-chain or core halogenation. Keywords: aryl halides; benzyl halides; bromination; sustainability; Introduction Activation through halogens has become a key strategy in achieving

• functionalisation on the aromatic ring when used in the dark [20]. A classic example is the bromination of toluene with molecular bromine. When the system is exposed to light (right side of Figure 1), a radical mechanism is initiated by Br• coming from Br2 homolysis. Propagation involves the reversible abstraction

• CCl4 to prevent undesired solvent degradation. Furthermore, the direct use of Br2, even if used in low concentration, exhibits limited selectivity towards benzylic bromination, primarily due to co-bromination occurring on the aromatic ring. This side process produces awkward halogenated byproducts that