Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• situ formation of an active enol ester 26. The phenol was formed in situ during the second step from phenylboronic acid oxidation utilizing H2O2 (30%) as green oxidant (Scheme 8B) [40]. Sureshbabu and co-workers (2023) activated the carboxyl group of 4-hydroxycinnamic acid (1) by selectively reacting

• CuBr promoted hydrogen atom abstraction from the amide 94 resulting in the benzylic radical species 95, followed by oxidation to give acyliminium species 96. Luque and co-workers (2020) developed a biogenic carbonate of CuO–CaCO3 to catalyze solvent- and additive-free amidation reactions in air

• reaction (143) to activate the isothiocyanate as the coupling partner (Scheme 44) [83]. On the other hand, nucleophile activation could also be achieved via a catalytic oxidation reaction. For instance, Ablajan and co-workers (2024) reported the preparation of phenyl cinnamate (24) starting from the acid

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

• the terminal alkene and the conformational strain of forming a bridge[3.2.1]bicycle might be responsible for a selective 6-exo-trig cyclization. From tricyclic compound 4, anti-Markovnikov oxidation catalyzed by palladium led to the formation of aldehyde 5. When treated with p-TsOH, the intramolecular

• on this strategy, the authors also accomplished the total synthesis of (−)-lycospidine A in only 10 steps [20], another Lycopodium alkaloid with a truncated tetracyclic skeleton and distinct oxidation levels, further highlighting the versatility and efficiency of the enamide aza-Prins approach

• a regioselective manner. From tetracyclic compound 11, a one-pot facial and regioselective hydroboration/amide reduction followed by oxidation produced (+)-lycoposerramine Q, which was then converted to (+)-fawcettidine by Ley oxidation. Alternatively, hydroboration of 11 in mild conditions without

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

• radical unit. Now, the chlorine substituents screen the hemispheres above and below this plane, protecting the unpaired electron in the p-orbital from oxidation or other detrimental degradation. The weak emission of PTM with ϕ of 0.7% peaks at 609 nm (in tetrachloromethane (CCl4)) [40]. The racemic

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• : alkene; amino-sulfonoxylation; metal-free; tethered nitrenium; Introduction Our laboratory has a programmatic focus on the development of metal-free oxidation reactions that avoid the use of toxic reagents such as osmium and chromium [1][2][3]. In line with this agenda, we recently explored a mild amino

• reagent served to initiate nitrenium formation and alkene oxidation. Not all sulfonic acids, however, were compatible with these conditions and were recalcitrant for steric or electronic reasons. For these acids, replacing 1-acetoxy-1,2-benziodoxol-3-(1H)-one with the more reactive iodomesitylene

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• the Eox of the D–A structures. For instance, IMD (b) with an oxidation potential of 0.73 V when present in the molecule 5b resulted in a considerably different Eox of 1.32 V (Figure 3). A molecule that in the excited state exhibits both strong oxidative power (E*ox up to −1.5 V) and strong reductive

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• tricyclo[4.2.110,30.11,4]decane ring system. Additionally, krishnolides A and C contain 9–11 stereogenic centers and exhibit diverse oxidation patterns. Their relative and absolute configurations were determined through NMR, HRESIMS and ECD experiments, as well as single crystal X-ray diffraction analysis

• molecules could be synthesized from diol 9 through a late-stage modification involving adjustment of the oxidation state and regioselective acylation. The formation of 9 was envisioned to proceed via an intramolecular pinacol coupling [30][31] of [5,5,6,6]-tetracycle 10, which forges the A2 ring while

• bicyclic ketone 21, which was prepared from (+)-Hajos–Parrish ketone in 49% yield over two steps (Scheme 3) [40][41][42][43]. Ensuring silyl enol etherification of the ketone at C29 coupled with IBX-mediated Nicolaou oxidation [44] furnished the corresponding enone in 72% yield (90% brsm). The methyl group

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• . Access to vicinal boron scaffolds 4f and 4g provided conclusive evidence that sensitization of alkenylboronic esters is achievable using xanthone, with in situ oxidation enabling direct access to otherwise challenging to synthesize cyclobutyldiols. The lower observed diastereoselectivity may reflect

• excitation [66][67], product derivatization was explored (Scheme 2A). While initial efforts for oxidation proved challenging, due to a competing retro-aldol ring-opening reaction, employing a buffered system enabled access to β-alcohol 5. Given the previous power of trifluoroborates in cross-coupling

• the substrate scope. Conditions: 3 (1 equiv), xanthone (20 mol %), MeCN (0.03 M), under 365 nm irradiation, rt, 16 h; axanthone (50 mol %) was used and reactions were run for 48 h; bto aid characterization of isolated material, the product was isolated after oxidation to the corresponding

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• response, respiratory, vasodilation, apoptosis, tumor growth, and cardiovascular system [1][2]. Nitric oxide (NO) is released as product of the NADPH and oxygen-dependent oxidation of ʟ-arginine to ʟ-citrulline under the catalysis of the enzyme nitric oxide synthase (NOS) [3]. There are three distinct

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

• . Electricity can perform the oxidation and reduction process by exchanging electrons on the electrode surface in a region called the double layer (DL) [12]. Unlike traditional methods that require high temperature, pressure, and external oxidants, electrochemistry is an efficient and energy-saving approach

• . They consist of two electrodes – anode (where oxidation occurs) and cathode (where reduction occurs) – immersed in an electrolyte. Galvanic cell The redox reaction occurs spontaneously in these cells, converting chemical energy into electrical energy. The potential difference between the two electrodes

• reaction. Some of their applications include hydrogen and oxygen production, metal electroplating, and organic compound synthesis using electrochemical methods. Depending on the reaction conditions, these cells can be divided or undivided. Divided vs undivided cells In divided cells, oxidation and

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

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• under constant current conditions in aqueous acetonitrile and provides access to N-sulfonyl, N-benzoyl, and N-Boc-protected 2-aminoproline derivatives. Keywords: anodic oxidation; decarboxylation; electrosynthesis; Hofer–Moest reaction; non-proteinogenic amino acids; Introduction Non-proteinogenic

• amount of water was reduced from 33% to 17% (Table 1, entry 8 vs entry 7), an observation that might be useful for substrates of low aqueous solubility. However, further reduction of water amount to 5 equivalents completely inhibited the anodic oxidation of 9a, and only traces of the desired 6a were

• F led to a drop in the pyrrolidine 6a yield due to the formation of a new side-product. We hypothesized that the side-product formation at increased amounts (>2.5 F) of passed charge results from undesired Shono oxidation of pyrrolidine 6a [10][11]. Indeed, CV studies of 6a revealed an irreversible

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• aggregation during photoconjugation reactions represents a major challenge for the stability and efficacy of conjugated antibodies [60]. Exposure of antibodies to light, particularly UV light, can trigger photoinduced reactions that compromise their structural stability. These phenomena include the oxidation

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• were optimized to achieve product 20 with 85% yield, minimizing potential side reactions. The subsequent dearomatization step is crucial for the construction of the cyclohexadienone unit. Oxidation of compound 20 with PIDA in trifluoroethanol, the original phenol was converted into a quinone moiety

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• reactions [10]. Oxidation of the alcohol is done in situ to avoid problems regarding the isolation and instability of the aldehyde produced, although undesirable reactions, such as oxidation of the amines or isocyanides or overoxidation of the alcohol, could also be problematic [11][12]. In this regard

• , several efforts have been made to improve the chemoselectivity of the oxidation step. Among the most relevant examples, o-iodoxybenzoic acid (IBX) has been used in Ugi and Passerini reactions to oxidize the suitable alcohol to the desired aldehyde [13]. Alternatively, catalytic amounts of a ternary system

• , in a recent work, Pan et al. could chemoselectively oxidize methanol using a TEMPO-catalyzed electro-oxidation process, even in the presence of oxidizable amines, such as benzylamine, paving the way for the use of methanol as a formaldehyde surrogate in these isocyanide-based MCRs (Scheme 3) and

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• to suppress undesirable fluorescence self-quenching [15]. Not only do bulky substituents disrupt intermolecular interactions of this type, they can also provide higher chemical stability and reduce or prevent the photodimerization and photo-oxidation to which all acenes are prone [13]. Furthermore

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

• with Grignard reagent, and oxidation with RuCl3/NaIO4. Keywords: aggregation pheromone; chiral 2-methyloxirane; red flour beetle; total synthesis; Introduction The red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), is a cosmopolitan, destructive stored product pest [1], which

• coupling, and finally leads to the target pheromones by olefin oxidation with RuCl3/NaIO4. Results and Discussion The retrosynthetic analysis of the aggregation pheromone (4R,8R)-1 is shown in Scheme 1. Obviously, the target pheromone (4R,8R)-1 could be synthesized via an oxidation of chiral terminal

• oxidation. The optical purity of the chiral secondary alcohol (R)-4 was more than 99% ee, determined by 1H NMR spectrum of its Mosher ester [27][28]. The subsequent tosylation with p-tosyl chloride gave (R)-hex-5-en-2-yl 4-methylbenzenesulfonate ((R)-5) in 88% yield [29]. The reaction of (R)-5 with the

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

• exposing fresh material to light. In 2016, König and co-workers exploited rod milling to develop a photomechanochemical approach for the riboflavin tetraacetate (RFTA)-catalyzed photocatalytic oxidation of alcohols to the corresponding carbonyl compounds upon irradiation with five LEDs (λ = 455 nm) [69

• oxidation of 1,2-diphenylethyne to benzil [71]. Thus, when a 1:2 mixture of 7.1 and 4-chlorothiophenol (7.2) was ground in the presence of eosin Y as the photocatalyst and anhydrous Na2SO4 as a bulking agent, benzil (7.3) was obtained in 43% GC yield under blue light irradiation (LED, 14.5 W). Isolation led

• oxidation of alcohols. The photos in Scheme 6 were reproduced from [69] (© 2016 M. Obst et al., published by Beilstein-Institut, distributed under the terms of the Creative Commons Attribution 4.0 International License, https://creativecommons.org/licenses/by/4.0). Photomechanochemical oxidation of 1,2

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

• diarylbromonium species by direct anodic oxidation of 2,2'-dibromo-1,1'-biphenyl. The electrochemical method provides access to a range of symmetrically and non-symmetrically substituted cyclic biaryl λ3-bromanes in moderate yields. Keywords: anodic oxidation; cyclic biaryl λ3-bromane; cyclic voltammetry

• oxidation of 2,2'-dibromo-[1,1'-biphenyl] into mono-λ3-bromane 5 would set the stage for the key cyclization event (Scheme 1, reaction 2). We also reasoned that an anodic oxidation of the aryl bromide is perfectly suited for the generation of mono-λ3-bromane 5 under mild conditions [16][17][18]. This

• an electrochemical synthesis of cyclic diaryl λ3-bromanes under anodic oxidation conditions. Results and Discussion Symmetric 2,2'-dibromo-1,1'-biphenyl 4a possessing ethoxycarbonyl groups ortho to the bromine was chosen as a model compound for our study. We anticipated that the presence of the ester

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

• , which can act as an oxidation catalyst (Figure 7C) [44]. The long-standing challenges of synthesis, stability, solubility and internal functionalization are beginning to be tackled, and the remainder of this Perspective will discuss specifics of these hard-earned advances and the opportunities they

• ) [38]. To capture both stability and solubility, we turned to Mastalerz’s post-functionalization chemistry [286][300][304][306][358][359][360][361][362], in which imines are oxidized by a Pinnick oxidation to amides [286][360][363][364], an approach gaining popularity [46][262]. Importantly, we were

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• synthesis of iVeliparib-AP6 [5] starts with a nucleophilic aromatic substitution (SNAr) reaction wherein 4-fluorothalidomide (1) reacts with amino-PEG7-OH 2 to give alcohol 3 (Scheme 1). Subsequent alcohol oxidation followed by reductive amination of the resulting aldehyde 4 with veliparib [6][7] provides

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

• first introduced the 2,2-dimethylpentenoate protecting group 32 (Figure 1) similar to the pivalate group which showed versatility in its cleavage principle [101]. Hydroboration oxidation of the olefinic bond helped in the removal of the protecting group. On the other hand, dihydroxylation with osmium

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

• -(indolin-2-yl)-5,6,7-trichloro-1,3-tropolones 7a,b is accompanied by dehydrochlorination of 6 upon boiling in dioxane according to method A. One of the conditions for carrying out the reaction according to method B is the use of a two-fold excess of quinone 3. Oxidation of dihydrotropolones 6 with an

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

• sustainable photocatalysis, with applications ranging from selective oxidation to cross-dehydrogenative coupling. These organic systems are valued for their reduced environmental impact, their wide availability, and tunability, making them viable alternatives to traditional metal-based catalysts for red-light

• own a large span of colors depending on the nature of the metal and the ligands but also on the various oxidation states these compounds can attain. This property results on the absorption of a visible-light photon complementary to the observed color and has been extensively exploited in photoredox

• 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

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

• bonding changes. Stretching force constants were evaluated to monitor the aromatic–antiaromatic alternation pattern upon oxidation. They showed us that the dication of linear [3]naphthylene became an overall global π-electron delocalized molecule. This result was supported by nucleus independent chemical

• shift (NICS) calculations and anisotropy of the current induced density (ACID) plots, as they evidenced the presence of a perimetral diatropic global ring current upon oxidation. Keywords: ACID; aromaticity; force constants; NICS; spectroscopy; Introduction Since the discovery of conjugated polymers

• attracted a growing interest in recent times, both from fundamental and technological reasons [9][10][11]. Antiaromaticity destabilizes the ground state of organic molecules by raising their highest energy occupied molecular orbitals, thus allowing for easy oxidation, doping, and electron-transfer reactions

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• properties were investigated by UV–vis absorption and fluorescence spectroscopy in compassion to pristine BPP and its oxidation product, benzo[rst]pentaphene-5,8-dione (BPP-dione). BPP-OiPr exhibited a significantly enhanced photoluminescence quantum yield (PLQY), reaching 73% in comparison to pristine BPP

• improving the stability of inverted perovskite solar cells [23]. On the other hand, benzo[rst]pentaphene-5,8-dione (BPP-dione) is known as an oxidation product of BPP [24][25], but to the best of our knowledge, the detailed optical properties of this BPP derivative have not been previously described in the

• reaction conditions to selectively obtain BPP-OiPr 3 in 55% yield from dialdehyde 1. Additionally, oxidation of BPP-OiPr 3 provided BPP-dione 4 in 70% yield. The photophysical properties of BPP-OiPr 3 and BPP-dione 4 were carefully studied, examining the solvent-polarity dependence of their optical spectra