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 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

• exceptionally high yield (97%). A Suzuki cross-coupling reaction between 47 and 45 gave compound 48 which was subjected to a final Scholl oxidation using DDQ. The target compound 49, containing two azulene subunits, was obtained in a relatively low yield (16%). Analysis of NICS values for 49 revealed similar

• oxidation of azulene units is particularly efficient when performed in an electron-deficient system, as demonstrated by Tani and co-workers [71] in their synthesis of azulene-fused tetracene diimide 107 from precursor 106 (Scheme 15). Oxidation with DDQ gave the target product in very high yield (95

• authors attempted to directly oxidize 170 to 172 using Scholl reaction. However, compound 172 was isolated in only 1% yield. As an alternative, they brominated 170 to form 171, followed by Yamamoto-type coupling using Ni(COD)2 and 2,2’bipirydyl (COD = 1,5-cyclooctadiene), which produced 172 in high yield

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

• the trend C–I > C–Br > C–Cl, consistent with bond dissociation energies (90g–j). Notably, deuterated chloroform was successfully employed to obtain deuterated oxindole 90k in high yield, demonstrating the method's potential for isotope labeling applications. A plausible mechanism, as outlined in

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

• reacting it with Eschenmoser’s salt, followed by hydrolysis with lithium hydroxide. The resulting unsaturated acid 54, isolated in 92% yield, underwent asymmetric hydrogenation using both (Ra)-50 and (Sa)-50 catalysts. This step provided the respective compounds 55 and 56 in excellent high yield and

• demonstrated when compound 100 was treated with MeMgBr/CuBr and either 94 or ent-94, affording 101a and 101b, respectively, with high yield and exclusive diastereoselectivity. Compound 101a, featuring the relevant stereochemistry of borrelidin at the C4, C6, C8, and C10, underwent Baeyer–Villiger oxidation

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• ]pyrazine was explored here for phenethylamine and 13 other liquid primary amines. This convenient synthesis involving only addition of liquid amine to starting material, and stirring at room temperature, was found to proceed readily within 6 to 16 h, in generally high yield. Exclusive tele-substitution (8

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

• acid (7-ACA) from cephalosporin C by cephalosporin C acylase [37], was used as a chiral starting material. After esterification of both carboxylic acid functions followed by cyclization to the lactam [38][39], the six-membered ring structure was established as (R)-methyl 6-oxopipecolate (7) with a high

• 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

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• obtained (S)-13k in good yield with moderate enantioselectivity. Furthermore, when (E)-1,3-di(p-chlorophenyl)-2-propenyl acetate (15) was utilized as an allylic acetate, the desired product (S)-13l was obtained in high yield with excellent enantioselectivity. We confirmed that the product 13 from the Pd

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

• -silyl substituted cyclopentanone 41, and acyl chloride 42 produced enamide 43. The polycyclization then took place under the catalysis of Cu(OTf)2/L3 and In(OTf)3, delivering tricyclic product 44 in high yield with excellent enantioselectivity. Despite formation of multiple diastereomers due to the

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

• regulating the chemical selectivity of a three-component radical cascade reaction involving α-brominated aryl ketones 72, olefins 73, and 1-methylquinoxalin-2(1H)-one (74) with an inorganic base, they were able to obtain two important types of products with high yield and enantioselectivity. Through

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

• converted to the desired nitrile 5g in high yield. Gram-scale reactions were conducted using allenes to demonstrate the practical applicability of this hydrocyanation method (Scheme 5). Allene 1q (1.04 g, 7.2 mmol) and allene 4b (1.08 g, 6.0 mmol) were effectively transformed into nitrile products 3q and 5b

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

• activities. Budnikova et al. [50] reported a C–P bond formation via the reaction of acridine compounds with trialkyl phosphites in electrochemical conditions without metal catalysts and strong oxidizing reagents, conducting selective C9 phosphorylation with high yield. The reaction was carried out in an

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

• optimization revealed LiOt-Bu and diphenyl phosphate as the optimal metal alkoxide and leaving group, delivering the desired product 32 in high yield and high enantioselectivity at room temperature with only 2 mol % catalyst loading. The scope of this transformation proved to be remarkably broad. In addition

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• attachment – a near two-fold decrease in yield was observed (H2a vs H2e), inferring that the reaction is strongly affected by steric effects. A high yield (78%) was also observed for the hydroxy-bearing hydantoin from threonine (H2g), suggesting that the reaction works smoothly in the presence of an electron

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

• ). Later, we evaluated the effect of the carbocyclic ring size, observing a high yield (up to 80%) when the 5-aminopyrazole 3ga prepared from cycloheptanone was used, while 5-aminopyrazole 3fa bearing a cyclopentenyl ring afforded alcohol 5faa with lower yield (27–44% yield). Unfortunately, in the case of

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

• ] or hydrazine dithiocarbonate [116][117]. Owing to its versatile selectivity, it has been widely used in oligosaccharide synthesis [118][119][120][121][122] to implement the neighbouring group participation protocol, thereby producing 1,2-trans glycosides in high yield and selectivity without

• [130]. The group has shown the formation of 1,2-trans glycosides with both carbohydrate-based and non-carbohydrate-based aglycons and carbohydrate acceptors in high yield. Continuing with the carbonyl-mediated glycosylation protocol, Wang et al. showed the application of the photolabile 2-(2

• -(phenylsulfanyl)ethyl moiety in the C-2 position led to the stereoselective formation of 1,2-cis glucoside and 1,2-cis galactoside in high yield by the formation of a quasi-stable anomeric sulphonium ion intermediate [150]. In continuation with the use of auxiliary protecting groups as the O-2 protection for

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

• in a high yield in the presence of ʟ-proline could be explained by the efficient crotonic condensation of formaldehyde and acetylacetone (1), followed by the addition of the second equivalent of diketone 1 to the highly reactive methylidene intermediate. The mild reaction conditions (room temperature

• , 2,3-dimethylbutadiene and isoprene. In reactions with Meldrum's acid, target products 10, 12 and 14 were obtained in a high yield. But for other CH acid derivatives, the reactions proceeded much less successful due to the side formation of products III. Under general conditions, the least active

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• ]. Control experiments were performed for the 3-thioflavone formation process. It was found that without the addition of sodium p-toluenesulfinate, 3a was converted to 4H-chromen-4-one (3aa) in high yield (reaction 3 in Scheme 5). When 3aa and 1a were used as substrates, product 4a could be obtained in high

• yield (reaction 4, Scheme 5). Additionally, the reaction of 3a with disulfide and thiosulfonate yielded product 4a in 49% (reaction 5 in Scheme 5) and 96% (reaction 6), respectively, confirming that the reaction proceeded mainly by the conversion of thiosulfonate to 3-thioflavone. In order to verify

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

• enantioselective C–H alkynylation of ferrocene carboxamides with terminal alkynes by using Cu/BINOL and an electrocatalytic system (Figure 5) [49]. 8-Aminoquinoline-assisted C–H functionalization provided planar chiral ferrocenes with high yield and enantioselectivity. This reaction can be applied to a wide range

• quinine as a chiral ligand under standard conditions, the chiral product was obtained with a high yield and 79% ee. Enantioselective C(sp3)–H functionalization is an attractive strategy for synthesizing chiral molecules. Significant progress has been achieved in transition-metal-catalyzed asymmetric C–H

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

• atroposelective deracemization of biaryl hydroxy aldehydes 55a–k [37]. NHC catalyst C18 afforded a range of axially chiral benzonitriles 56a–k in high yield and enantiomeric purities (Scheme 18). The reaction likely proceeds via the initial formation of racemic imines, which is followed by the formation of aza

• naphthyl and phenyl substituents provided satisfactory to good yields in general with high degrees of enantiomeric purity. Scaling up the reaction to a one-mmol scale with reduced catalyst loading of 5 mol % resulted in high yield and slightly decreased enantiomeric purity for the representative product

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• glutamate) (PBLG) as the hydrophobic block, which was done to prevent ending on a primary amine in the final product which could disrupt self-assembly due to its ionizable nature. Subsequently, PBLG served as a macroinitiator for the polymerization of sarcosine NCA, yielding the final polymer with high

• yield and low polydispersity index (PDI), crucial for effective self-assembly [29]. Previous studies on PEG-PS vesicles demonstrated a solvent-exchange method for vesicle formation, followed by a shape transformation induced by osmotic pressure from PEG addition [18]. The structure was then frozen by

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• free naphthol group in high yield (91%). We next turned our attention to the synthesis of benzo[j]fluoranthene 28, which is structurally related to 23, but with a free -OH group at a different position (Scheme 4). Our synthetic sequence commenced with the preparation of the known bromonaphthol 29 in

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

• prepared in high yield via FeCl3-oxidative coupling of 1,2-dialkoxy-4-bromobenzene (Scholl reaction). The new triphenylene derivatives, F3–F12, were prepared in moderate to high yields (51–73%). In addition, three bitriphenylene derivatives were synthesized in a subsequent annulation step from Fn

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• a single oligomer across a panoply of different transformations typically range from <1% to ≈30% when n > 1 is desired [35]. To the best of our knowledge, the assembly of functionalized [n]staffanes from 1 in high yield/selectivity and in one step via controlled radical oligomerization remains a

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

• in a high yield. In this reaction, the size of the end-capping agent is the key, as an extremely large reagent does not react well with the amino axle-end groups, whereas an extremely small reagent cannot function as an end-cap. This reaction exhibits the following multiple advantages compared with

• structure analysis, and is purified by simple precipitation without requiring chromatography; (3) various end-capping agents are available, and well-optimized conditions can ensure a high yield (e.g., 2-methoxyphenyl isocyanate obtains an 85% yield after 3 h of reaction [49]). Owing to such a high-yield

• considerably studied. However, in a small-molecule system, high-yield synthesis is still not so conventional except with the urea end-capping method. In the next section, the structural regulation system is explored and discussed in terms of its applicability to polymer systems. Structural control of the (poly