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

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• ]pyrrole α,β-isomer 4 was found to be catalytically active providing a 57% conversion to 10, suggesting a concerted cycloaddition mechanism. Calix[4]pyrrole α,α-isomer 3 and dipyrromethane 5 were catalytically inactive. The authors concluded that the catalytic inactivity of 3 is caused by the parallel

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• backbone adopt a nearly parallel orientation with a slight tilt compared to the horizontal axis which results in one short (Figure 3a, left ligand: 2.2 Å, and right ligand: 2.3 Å) and one longer Htriazole···Hquinolate (Hg···Ha) distance (left ligand: 2.8 Å, and right ligand: 2.8 Å). Contradictory, the

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• hypervalent R–I–X bond and the plane of the arene substituent (Figure 3c): When the plane of the arene ring was parallel to the R–I–X bond (φ < 5°), relatively stable compounds ensued, while a large twist away from planarity resulted in compounds that were destabilised towards thermal decomposition. For

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• and breast carcinoma MCF7. In parallel, human skin fibroblasts were used as reference for non-tumor cells and roscovitine (ROSCO), doxorubicin (DOXO) and Taxol as positive controls. For details see: ref. [2] and Supporting Information File 1, Table S1. Compounds 4a–f, 4h, 4i, 4k, 4l, 4o and 4q that

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• clearly arise from repulsion of the axial fluorine at C2 and the axial halogen at C4 as exemplified with the H3–C3–C2–F2 and the X4–C4–C3–H3 torsion angles being smaller than the expected 180° (Table 3, entry 16 and 17). The 1,3-diaxial repulsion leads to a deviation from parallel alignment as shown in

• Table 4. The Newman projections of the halogenated analogues show deviations from parallel alignment for the C2–F and C4–X substituents of 12.08° for 17, 17.08° for 13, 18.18° for 14, and 18.59° for 15 (talopyranose, 18: 5.92°). This deviation is responsible for the distance between F2 and the halogen

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• disease [2][3]. In parallel, mass spectrometry (MS) has been crucial in many areas centered around the characterization of NPs [4]. First to annotate their often complex structures using diverse fragmentation techniques [4]. Nowadays, MS is applied for the identification of NPs’ cellular protein targets

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

• also the structure for which the descriptors are considered. This can either be ensured by expert-knowledge of preselecting relevant structures, for example based on a known mechanism, or by considering information from the entire conformer ensemble. Parallel to the evolution in modelling steric

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ) [43]. In parallel, Sheng and Zhang et al. found that 2-(1,3,4-oxadiazol-2-yl)aniline derivatives 38 could be electrochemically synthesized from isatins 35 and acylhydrazine 36. The transformation was carried out in an undivided cell at high temperature in DMSO using potassium iodide as supporting

• electrolyte ammonium acetate and the alcoholic solvent acted as N and C1 sources, respectively. The authors proposed the mechanism depicted in Scheme 10. The deprotonation of hydrazone 52 afforded anion 54 which underwent SET anodic oxidation to form radical 55. In parallel, an elusive oxidation of alcohol

• oxidation of N-arylhydrazone by electrogenerated iodide radical (Scheme 11) [50]. In parallel, the group of Yuan achieved the electrosynthesis of 1,3,5-trisubstituted 1,2,4-triazoles 67 from arylhydrazines 64, aldehydes 65 and primary amines 66. Iodine-mediated electrooxidation of in situ-generated aldehyde

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• and 3, their conformational ensembles, datasets of a structure and population of each conformer [25], were determined using a Spartan 24 parallel package conformational search tool (Wavefunction Inc, USA), followed by geometry optimization of the most weighted conformers (Boltzmann distribution weight

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• allow the reaction to take place under the mildest possible conditions. This search goes in parallel with the urge to use increasingly diverse and complex building blocks, up to and including DNA conjugates, which would be degraded under the classical conditions developed by Groebke, Blackburn and

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• stereoselective cyclization reactions. This review aims to provide an overview of these approaches and parallel comparisons with original biosynthetic pathways by highlighting five examples of chemo-enzymatic total syntheses of natural products reported since 2017. The examples are the synthesis of cotylenol (1

• aromatization provides chalcone 43. Prenylation of the resultant aromatic ring of 43, catalyzed by MaIDT (Morus alba isoliquiritigenin 3-dimethylallyltransferase), leads to morachalcone A (44) [50][51]. In parallel, benzofuran 46 was biosynthesized from 4-coumaroyl-CoA via thioester 45. Further prenylation of

• classification, along with parallel discussions of the original biosynthetic pathways, helps organize the current state of the art and offers a comprehensive overview of how synthetic methodologies leverage the natural biosynthetic pathways. The development and optimization of chemo-enzymatic synthetic processes

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• . Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Akademik Kukhar Street 1, Kyїv 02094, Ukraine 10.3762/bjoc.20.143 Abstract Parallel Groebke–Blackburn–Bienaymé reaction was evaluated as a source of multimillion chemically accessible chemical space. Two most popular classical protocols

• last two decades, the GBB reaction has been studied in more than 200 research papers [21] and a number of works (including the original publication by Blackburn and coauthors [20]) described its parallel synthesis version [24][25][26][27][28][29]. Recently, we have shown that other (pseudo-)three

• the corresponding library members were denoted as 4{i,j,k}. Results and Discussion Library synthesis Preliminary experiments on the parallel GBB reaction were performed with heterocyclic amines 1{1–430}, aldehydes 2{1–583}, and isonitriles 3{1–73} available from our stock (based on our previous in

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• Discussion This study evolved from a parallel exploration of reactions involving unsymmetrical phenyl(mesityl)halonium salts, i.e., Ph(Mes)X+. DFT analysis revealed similar structural trends to our previous work [21] when we expanded the halogens to include astatine (At). Due to its radioactivity and short

• points, in which XB donors with larger Vs,max values also had more exergonic associations, we actually observed two almost parallel clusters of data (Scheme 6c). In this case, neutral XB donors 26–28, and 30–36 had Vs,max values ≈5–50 kcal/mol and a slope of −0.24 (Scheme 6c, light grey dots), whereas

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• , promoting, via hydrazone–enamine tautomerization [17][24][25], the nucleophilic addition which concludes with the construction of the heterocyclic N,O-aminal 5 through the intramolecular N–C bond formation. The FeCl3 can also interact with the newly formed N,O-aminals 5, giving rise to the second parallel

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• corresponding ESP maps. A comparison of the ESP maps of 3a and hydrocarbon [6]CMP showed induction of biased densities by the nitrogen dopants. Similar biased densities were previously found to be critical in determining the packing structures of nitrogen-doped π-systems to make parallel-displaced

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• as a cofactor [10][11][12][13]. The parallel behavior of Flu17 and AlpJ in the reaction with 8 provides additional support for the shared oxidative B-ring cleavage and contraction steps in the biosynthesis of fluostatins and kinamycins. Nevertheless, the mechanism by which a B-ring-contracted

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• validation report can be generated for each carbohydrate in the molecular model. This report is put out in JSON format for easy consumption by web-based database frontends. The initial report generation was completed in parallel over 64 CPU cores in around 5 h. After the initial surveys through PDB and PDB