Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• ). Further geometrical adjustment and conformational restriction of the transient structure enable the N9 nonbonding p orbital to align parallel to the σ(C19–C3)* orbital (Figure 2f, TS2 → F-10 → F-40 → IN3), which reinforces the hyperconjugative interaction. Facilitated by the bond stretching and bond-angle

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• between 10 µM and 30 µM, and poor under 10 µM. Compounds with no value were under the detection limit. As a result, seven compounds had good solubilities: (E)-7c, (Z)-7c, 7d, 7e, 3b, 3c, and 3e. We also carried out a gastrointestinal parallel artificial membrane permeability assay (GI PAMPA). The

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• synthesis of amines by replacing the current toxic pathway based on ethylene oxide and dichloroethane [29]. Due to the high reactivity of α-hydroxycarbonyls, the main issue in this reductive amination reaction [30] was to control the cascade of consecutive and parallel reactions. The use of methanol as

• ][87][88][89][90][91][92]. Essayem and co-workers reported the conversion of DHA with the help of TiO2-based catalysts having dual properties. Two parallel pathways are as follows: on one hand the catalyst Lewis acidic sites promote the formation of pyruvaldehyde and lactic acid (LA) by a two-step

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• similar compounds based on 5-amino-1H-pyrazole-4-carbonitrile [22]. It should be noted that diazocines 4 were stable and did not undergo transformations when heated or irradiated with ultrasound. This may indicate that pyrimidine-7-carboxylic acids 5 and 6 are formed in parallel processes under kinetic

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• coplanar with a dihedral angle of 170°. The two dichlorobenzene rings are parallel to each other and perpendicular to the pyrene plane, and the four tert-butylphenyl groups are directed on one side of the pyrene plane to minimize steric repulsion. MC2 takes a C2v-symmetric saddle-shaped geometry with two

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• -diimines. Later, in 2001, Yudin and co-workers described the parallel reductive coupling of aldimines using a spatially addressable electrosynthesis platform, which employed a stainless steel cathode, a sacrificial aluminum anode and a procedure adapted from Torii's earlier work including the use of PbBr2

• , TFA, and Bu4NBr [45]. Under these conditions, parallel electrosynthesis allowed the synthesis of up to 16 vicinal diamines in good yields in 30 minutes. To the best of our knowledge, the most recent example of electroreductive coupling of imines was reported in 2025 by Wang’s research group [46], who

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• antiparallel conformation (Scheme 41). However, open-ring diarylethenes usually consist of an equilibrium between a parallel conformation (not active) and antiparallel (active). For some examples, the equilibrium was also found to be affected by the polarity of the solvent: polar solvents could stabilise the

• parallel excited state because of the larger dipole moment [121]. To enrich the population of the antiparallel (and thus increasing the quantum yield of cyclisation), bulky substituents on the 2,2’ positions of benzothiophene were added [122], also the antiparallel conformation could be fixed by

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

• rely on specific properties such as dielectric anisotropy, where the molecular dipole moment aligns parallel to the molecule’s long axis [19]. Compound 1.2.3-c.c. exhibits a "Janus"-face-like structure, characterized by a positively charged region on one side and a negatively charged region on the

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• •NO2 radical substitution mechanism during the HNO3-mediated nitration of arylboronic acids, providing mechanistic justification for this synthetically valuable transformation [58]. Parallel evidence came from Plouffe and colleagues microreactor studies on salicylic acid nitration, where kinetics

• nitration process using continuous-flow, several approaches are listed in the literature, e.g., external numbering up, internal numbering up and sizing up [74]. In the numbering-up approach, ensuring a uniform flow distribution in parallel channels is difficult. The numbering-up approach inherently

• struggles with uniform flow distribution across parallel microchannels due to manufacturing tolerances, reactor fouling-induced pressure imbalances, and gas bubble entrapment, leading to localized deviations in nitration kinetics and consequent product quality inconsistencies in industrial-scale operations

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• chiral catalyst. Central-to-axial chirality transfer In parallel with Zhu’s work, Du, Chen, and co-workers reported an alternative way for the preparation of axially chiral 3-arylpyrroles [41] through a catalytic asymmetric Barton–Zard reaction [42] via central-to-axial chirality transfer strategy [43

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• influence of MW irradiation in the enhancement of the reaction rate for the CuCl-catalysed reaction, we carried out the model reaction in parallel, using both an oil bath and MW irradiation at 60 °C. Figure 2 clearly shows that MW irradiation drives the reaction to completion in 2 hours. By contrast, the

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• , or selenium enables spectral tuning across the visible to near-infrared range, improved photostability, and dual-state emissive behavior. In parallel, significant progress in synthetic methodologies – including enantioselective catalysis, electrochemical cyclizations, and multicomponent reaction

• nm) attributed to reversible intramolecular charge transfer [20]. In parallel, several groups explored the functional versatility of heterohelicenes in device-oriented and sensing applications. Crassous’s group synthesized bipyridine-embedded helicenes via the Mallory reaction, enabling coordination

• solvents, highlighting their potential for NIR bio-imaging applications. In parallel, Církva’s group synthesized a series of aza[n]helicenes 14a–d via photocyclodehydrochlorination [27]. These compounds exhibited dual fluorescence bands, with emission red-shifting progressively with increasing helical

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 narrow optical gaps. A striking example is the perylene isomer 172, which displays absorption extending to 1720 nm and an electrochemical gap of just 1.07 V [104]. The presence of two parallel azulene moieties in this structure results in an enhanced dipole moment (1.97 D) compared to pristine

• azulene (1.28 D). This parallel alignment appears to be critical for achieving a narrow optical gap: in contrast, a recently reported azulene dimer with antiparallel azulene units exhibits a lowest-energy transition at 680 nm [116], comparable to that of pristine azulene. However, the molar extinction

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

• % 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

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

• ). Reactions were set up in tandem and samples from both reaction vessels were taken, at 2, 4 and 6 h time points and used for TLC analysis to monitor reaction progress. The reactions proceeded in parallel, and both reactions had reached completion at 6 h. After isolation in high purity (≥95%) by silica flash

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

• ground state with parallel spins and S = 1 for the diradical molecule. Whether a molecule has a singlet or triplet ground state can be expressed by the energy difference between the first singlet and first triplet states ΔEST. When the energy difference is negative, ΔEST < 0, the diradical exists in a

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

• emerges. The 1,3-C–F bonds tend to avoid a parallel alignment, due to dipolar repulsion (III, Figure 3) [30][31][32]. This phenomenon can be harnessed to control molecular conformations in a predictable way, and once again the stereochemistry is important. For example, compare the natural product

• analogues 18 and 19 (Figure 3) [30][33]. Compound 18 contains a 1,3,5-trifluoroalkane moiety with syn,syn-stereochemistry, and it is found to adopt a bent alkyl chain which is necessary for the avoidance of parallel 1,3-difluoro alignments [30]. Compound 19 also contains a 1,3,5-trifluoroalkane moiety, but

• it has anti,anti-stereochemistry and now this portion of the alkyl chain is able to adopt an extended zigzag conformation without incurring any parallel 1,3-difluoro alignments [33]. Other fluorine patterns have been shown to control molecular conformation when embedded in the middle of an alkyl

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

• phosphate. The absolute stereochemistry of the products was found to be consistent with that of previously reported CuH-catalyzed transformations using (S,S)-Ph-BPE (L1) as the supporting ligand, suggesting a common mode of stereoinduction. In parallel, Hoveyda and co-workers demonstrated the first copper

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• E. M. Kosower in 1978. In this study, we report the topochemical cycloaddition of diethyl 2,6-dichloro-1,7-dioxo-1H,7H-pyrazolo[1,2-a]pyrazole-3,5-dicarboxylate (Cl2B), initiated by visible light. Crystal structure analysis confirmed that the reactive double bonds are parallel and coplanar, in line

• ] cycloaddition reactions, states that for the reaction to occur, the distance between the centers of the double bonds must be less than 4.2 Å, and the double bonds must be coplanar and parallel [11]. Designing topochemically active compounds is a challenging task, as the crystal packing mode must first be

• is 0(0°), indicating that the reacting double bonds are coplanar and parallel. Furthermore, the intermolecular distances between the reacting carbons are identical. The distance between two carbon double bonds in Cl2B (B) was determined to be 3.487(4) Å (Table 1). The key question is why did Cl2B

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• -electron contributions) for a perpendicular magnetic field over a plane 1 a.u. above the molecular plane of the pyrazole ring of the o-carborane-fused pyrazoles. Red/blue arrows when the component parallel/antiparallel to B is greater than 30% of the vector modulus. Diatropic/paratropic circulations are

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

• source at 660 nm led to a reduction in the isolated yield from 70% to 56%. Despite the full conversion of the starting material, the overall efficiency was hindered by the formation of side-products. Furthermore, various nucleophiles were found to be compatible with this transformation. In parallel the

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• utilized numerous times in medicinal chemistry campaigns as hits, leads and eventually even drugs, such as 2-aminothiophenes, -quinolines and -indoles [42][43][44][45]. Synthetic exploitation The synthesis of the key cyanoacetamide building blocks was our primary objective. In a parallel setup, a variety

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

• obtained 15 diversely substituted heteroannulated pyrimidones, employing privileged thiophene, quinoline and indole scaffolds in a rapid fashion, without the need of column chromatography, in a parallel setup. Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• , particularly π-stacking interactions between the aromatic rings in a parallel fashion from both host and guest, which is demonstrated by the crystal structure of the key element of the recognition motif. Results and Discussion Backdrop for design considerations Our interest in macrocycle-mediated

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

• constraints of parallel reactors that share the same MTP. In addition, challenges arise when standard MTP-based reaction vessels are used at a temperature near the solvent's boiling point, as this labware is not enclosed or able to cool the top of the reaction vessel to facilitate reflux conditions. Although

• of parallel flow reactors, where several distinct reactions conditions are tested simultaneously, has been proposed as a pathway to increase the throughput of flow reactions. Ahn et al. [54] designed and fabricated a complete prototype equipped with a unique built-in flow distributor (Figure 4) and

• 16 microreactors capable of executing diverse conditions in parallel, including photochemistry. The temperature of the capillary reactors can be controlled independently, providing flexibility in experimentation. The reservoir-type distributor, featuring a baffle structure, not only ensures uniform