Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• formation and N-Boc-protection [24] provided nitroarene 5 in 40% yield over three steps. Reduction of the nitro group was performed with Pd/C and hydrogen to obtain aniline 6 in 98% yield, which served as a precursor for mono- and dimethylated unit B derivatives 7 and 8, respectively. While dimethylaniline

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• -amine reduction and tosylation from diethyl (S)-2-(hex-5-en-2-yl)malonate ((S)-6). The stereocenter in geminal ester (S)-6 could be derived from (R)-2-methyloxirane ((R)-2) via a ring-opening reaction and a stereospecific inversion of the chiral secondary tosylate (R)-5. Following the similar procedure

• , geminal acid (S)-7 was decarboxylated with DMSO to yield chiral acid (S)-8 [33], followed by TiCl4-catalyzed reduction with ammonia-borane to obtain the chiral alkenyl alcohol (S)-9 [34]. The final tosylation with p-tosyl chloride provided (S)-3-methylhept-6-en-1-yl 4-methylbenzenesulfonate ((S)-10) [29

• ]. Similarly, chiral tosylate (R)-10 could be prepared from (S)-2-methyloxirane ((S)-2) through the ring-opening reaction, tosylation, stereospecific inversion, hydrolysis, decarboxylation, reduction, and second tosylation (Scheme 3). With two the chiral building blocks (R)-10 and (S)-10 in hand, we next

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• because the design of a photoswitchable agent usually starts with a known, non-switchable drug or a known biological molecule, which is already carefully "optimized" either by pharmaceutical industry or by nature. Hence, there is a high risk that any change in structure will also lead to a reduction in

• except the preparation of the aminoaniline building block tert-butyl (2-amino-5-bromophenyl)carbamate (5), which was prepared by Boc-protection of the 5-bromo-2-nitroaniline (6) and subsequent reduction of the nitro group (see Supporting Information File 1, section II.1). Cross-coupling reactions Stille

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

• -diaminopyrimidin-4(3H)-one to afford preQ0 (7), as originally reported by Townsend et al. [30]. The next step, namely the reduction of the nitrile moiety by hydrogenation is critical and notoriously difficult due to the low reactivity of this group in preQ0 [26]. We solved this problem by applying strongly acidic

• -step synthesis of O6-methyl preQ1 (16, m6preQ1) [28]. The direct reduction of the precursor O6-methyl preQ0 (15, m6preQ0) was possible, eliminating the need for the previously introduced protection/solubility concept, which shortened the synthetic route to only four steps (Supporting Information File 1

• of the electrophile. We thus identified aldehydes 9 and 10 as suitable branching points, which were easily derivatized to their aminomethyl-modified preQ1 analogs by reductive amination (Scheme 3). Their syntheses by Raney-Ni reduction of nitriles 7 and 8, previously described by Gangjee and co

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• , as a beam of light traverses through a solution, photons are quickly absorbed, resulting in abrupt reduction in light intensity. Thr Beer–Lambert law imposes the most stringent constraints from a practical point of view, mainly in terms of scalability. This requires highly diluted solutions, which in

• yield of 79%. Scanning electron microscopy (SEM) analysis revealed the deformation and reduction in size of SAOED particles upon milling. Interestingly, carbon determination experiments revealed that SAOED is quickly poisoned by organic matter, thus hampering recyclability. This can be to some extent

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• extractive workup followed by reversed-phase chromatography and its structure was unambiguously confirmed by X-ray crystallography (Table 1, graphic). Gratifyingly, a two-fold increase in the yield was achieved by a slight reduction of the current density to j = 8 mA·cm−2 (entry 2 vs entry 1 in Table 1). A

• ) experiments (0.1 M TBA-BF4 in HFIP on a Pt disk electrode) revealed that the reduction current increases almost 4 times upon the addition of 5 mM 1a to the electrolyte (see Supporting Information File 1, Figure S1). At the same time, passing 6.0 F through a solution of 1a in 50 mM TBA-BF4/HFIP at j = 8 mA·cm

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• ][344][345], which show early promise for low-symmetry cavities with catalytic potential [42][43][44][340]. Notably, Otte has used semi-stepwise self-assembly via imine formation/reduction to access a robust organic cage with reduced-symmetry and internal functionality able to chelate a copper(I) ion

• , organocatalytic motifs, and functional triads in precise-enough ways to permit a new wave of enzyme model studies, this time to reveal details of electric field catalysis [99][417][438][439][440] and the elusive roles of enzyme dynamics [395][401][441]. Catalytic rate enhancements from a reduction in the Gibbs

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

• used for glycosylation reactions in combination with the PIFA-TfOH reaction system. MeTetMe was particularly effective and could be orthogonally removed under Birch reduction conditions. Inference on neighbouring group participation Thus, we see that the electron-withdrawing groups like an ester

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• equation formalism (IEFPCM) [38]. Biological experiments The MTT colorimetric test for cell viability assessment is based on the reduction by NADPH-H-dependent cellular oxidoreductase enzymes of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, which has yellow color, into

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• ) begins with an acetate moiety that is extended six times by HR-PKS, programmed C-methylations took place after the first and second extensions with a cycle of full reduction occurring after the first extension. Subsequently, four acetate extensions with programmed reductions and dehydrations to afford β

• viability at concentrations as low as 3.9 µg/mL for farinosone D (1) and 1.9 µg/mL for farinosone A (2), as demonstrated by the XTT assay. This reduction in metabolic activity may explain why S. aureus was unable to form robust biofilms, as reflected in the CV biofilm inhibition assay. Therefore, it can be

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

• have been proven to be efficient in photoredox catalysis [9][10][11][12]. Actually, MLCT enables a charge separation for which the ligand-based electron can trigger a chemical reduction while the metal-centered hole, a chemical oxidation. This type of excitation is particularly enhanced in heavy metals

• reduction potential to −0.97 V vs SCE, a value low enough to reduce the ruthenium complex 2, whose potential is estimated at −0.89 V vs SCE, thereby yielding 3, the active species for the metathesis reaction. The catalytic cycle is closed by the reduction of the resulting osmium(III) complex, regenerating

• -bismuthinidene complex can drive formal oxidative addition even with substrates that exhibit high reduction potentials such as aryl iodides and aryl thianthrenium salts, thereby expanding the scope of aryl electrophiles that can be subjected to oxidative addition. This mechanistic advancement, combined with the

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• such as DABCO, DBU, triethylamine, and K2CO3 also resulted in the significant reduction of the yields. Therefore, the reaction of MBH nitrile of isatins and arylamines can be simply carried out in toluene at room temperature in the presence of a catalytic amount of DMAP. With the optimized reaction

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• significantly higher than the reduction of force constant of the CC bonds shared with the adjacent NAP rings, which justifies the wavenumber upshift from 1689 to 1713 cm−1 on the ν(CC)exo-CBD Raman band in the dication. Despite the symmetry lowering with respect to m-1, D2h → C2h, the force field of neutral m-2

• reduction of 53% with respect to m-1. On the contrary, the decrease for the d bond (NAP adjacent) from m-2 to m-22+ is 0.77 mdyn/Å, i.e., 30% higher than in m-1. In the case of the j bond, which is shared by CBD and NAP, both trends compensate each other, as its k[ν(CC)] decreases, upon double oxidation

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

• tetrabutylammonium iodide (TBAI)/H2SO4 reduction system using sodium sulfinate as key component, thus eliminating the need for thiols and redox reagents commonly used in traditional methods. Various disulfides and 3-sulfenylchromones were obtained in moderate to excellent yields through this methodology. Mechanistic

• the reaction, an attempt was made to increase the concentration, reducing the amount of solvent to 1 mL (Table 1, entry 12), product 2a was obtained in 67%, and a further reduction to 0.5 mL failed to increase the yield significantly (Table 1, entry 13). Although the amount of solvent used could have

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• Synthesis of primary amides via the generation of copper–imidate radical intermediates In a subsequent study, the research group of Son developed a method for the reduction of dioxazolones to synthesize primary amides under mild reducing conditions in copper catalysis (Scheme 10) [103]. The reaction was

• of alkynes. Proposed catalytic cycle for the copper-catalyzed reduction of dioxazolones. Formation of isocyanates and amidated arenes from dioxazolones. Copper-catalyzed synthesis of δ-lactams via open-shell copper nitrenoid transfer. aCuBr (10 mol %) and BOX-1 (15 mol %) were used. bA stereoisomeric

• of primary amides through N–O bond reduction using reducing agent. Funding This work was supported by the National Research Foundation of Korea grant (RS-2024-00333890) funded by the South Korean Government (MSIT). This work was also supported by the Korea Environment Industry & Technology Institute

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• constructs. Although many of the CF2H HB donors studied here can promote relatively strong hydrogen bonding interactions with n-Bu3PO, even the strongest CF2H HB donor (3b) is still 30 times weaker than phenol (10), corresponding to about a 2 kcal/mol reduction in binding energy at 25 °C. These results

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

• terminal alkyne 2 in the presence of a chiral copper catalyst and base, which reacts with the electrophilic iminium intermediate 15 to yield the desired chiral product 14. Active Cu(I) is regenerated either through cathodic reduction or by reaction with TEMPO–H. A year after the Mei group’s report, the Xu

• Pt surface for proton reduction, and offering anodic overcharge protection to avoid undesirable substrate oxidation. Conclusion Over the past two decades, significant progress has been made in electrochemical organic reactions, supported by the development of more sustainable and versatile

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

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

• present on the amino group of the 1,3-benzenediamine, lower yields were reported, and substituting the amino group in position 3 for an N-methylamino or N,N-dimethylamino group led to a reduction in the enantioselectivity. Shao et al. developed the first organocatalyzed atroposelective Friedländer

• intermediate Int-53. Control experiments confirmed that this structure could undergo successive reduction and oxidation through intermediate Int-54 to give benzylimine intermediate Int-55. Alternatively, a direct [1,5]-H migration of Int-53 also leads to Int-55. The stereoselectivity of the product is

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• Aalborg, Denmark current address: Centre for Analysis and Synthesis, Lund University, Naturvetarvägen 14, 223 62 Lund, Sweden 10.3762/bjoc.21.4 Abstract Phenethylamines and phenylisopropylamines of scientific relevance can be prepared with a NaBH4/CuCl2 system in 10 to 30 minutes via reduction of

• ), and appetite suppressants (e.g., phentermine) [6]. Phenethylamines can be produced via numerous different procedures [7]. One of the oldest methods involves the reduction of benzyl cyanide with H2 in liquid ammonia with Raney-Nickel catalyst at 130 °C, and high pressure [8]. Another known method is

• ]. One of the most studied and inexpensive routes to synthesize substituted phenethylamines focuses on the reduction of their α,β-unsaturated nitroalkene analogue (β-nitrostyrene), where both the double bond and the nitro group need to be reduced to deliver the corresponding primary amine. Their

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

• better performance in comparison to existing commercial software. In particular, HappyTools showed an enhanced throughput, demonstrating up to a ten-fold reduction of the total processing time for biopharmaceutical samples. The authors have released the source code and an executable program in an online

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• was achieved in 5 steps starting from commercially available 2-bromo-4-fluoro-1-nitrobenzene (1, Scheme 1 and Scheme 2). For the preparation of the key intermediate 5 (Scheme 1), self-coupling of 1 in the presence of copper followed by reduction of the nitro group generated diamine compound 3 (89

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• conducted at room temperature for 20 hours, which resulted in a reduction of the yield for 5aa to 9% (Table 1, entry 5). This result might be due to the reactivity of this hypervalent iodine reagent. Indeed, we have previously observed that the transfer of the benzylamine moiety to carbon-based nucleophiles

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

• features, with small fraction of dark area, which could be possibly attributed to a reduction of the mesophase symmetry. The results of the differential scanning calorimetry (DSC) are summarized in Figure 4 (see also Supporting Information File 1, Figures S37, S38 and Table S5 for details), confirming the

• , with a multitude of sharp peaks, that could be indexed according to a rectangular lattice (p2gg symmetry) [50], confirming the reduction of the phase symmetry and well-defined interfaces between aliphatic continuum, hydrogenated aromatics, and fluorinated arenes. The S/WAXS patterns of the three

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• –activity relationship data, leading to speculation over the moieties responsible for their antibiotic effects. A reduction in the number of amines in the polymeric chain and the absence of a primary amine was noted to decrease bioactivity by Xu et al. [7]. Research reported by Khan et al. in 2014 [9] also

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• substituted 1,4-benzodiazepin-3-ones using the UDC method. This process involves N-Fmoc-amino acids, isocyanides, amines, and derivatives of 2-fluorobenzaldehyde (Scheme 15). Ugi-4CR/reduction/cyclization (URC) strategy: The URC pathway enables the synthesis of benzodiazepines by using amine surrogates, such

• -carboxamide-1,4-benzodiazepin-5-ones when enantiopure (S)-(−)-α-methylbenzylamine and arylglyoxals were used. Thus, a reversal of diastereoselectivity was observed depending on the cyclization methodology employed, the reduction of a nitro group or the Staudinger/aza-Wittig on azide derivatives. This

• -benzodiazepin-5-ones employing Ugi–reduction–cyclization (URC) approach. Ugi cross-coupling (U-4CRs) to synthesize triazolobenzodiazepines. Azido-Ugi four component reaction cyclization to obtain imidazotetrazolodiazepinones. Synthesis of oxazolo- and thiazolo[1,4]benzodiazepine-2,5-diones via Ugi/deprotection