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

• synthesis of various benzoxazole derivatives, demonstrating its versatility and practical applicability. Keywords: aerobic oxidation; copper; grafted silica; heterogeneous catalysis; microwave; Introduction 2-Aminoazoles are nitrogenous heterocyclic compounds of high relevance due to their biological and

• developed for the amination of oxazoles, with many of them utilizing aerobic oxidation to improve the sustainability of the process. Indeed, in 2011, Guo et al. [45] developed a protocol for the direct C–H amination of benzoxazoles and oxadiazoles, under an O2 atmosphere using 20 mol % of a Cu(II) catalyst

• open derivative, and the subsequent ring oxidation upon closure (as shown in the mechanism in Scheme S1 (Supporting Information File 1), the reaction mixture may contain the desired 2-substituted benzoxazole 2a together with its open-form precursor 2a-o. The latter can be hydrolysed to give N

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

• with Ru(II) to form NIR-emissive complexes that exhibit redox-responsive chiroptical switching, notably with complex 8 showing reversible electronic circular dichroism (ECD) upon oxidation [21]. Liao and co-workers introduced a narrowband CP-TADF emitter 9, characterized by a narrow emission bandwidth

• BCPL value of 13.2 M−1 cm−1. Notably, compound 21c undergoes reversible redox interconversion to its radical cation 21c•+ and dicationic 21c2+ states via chemical oxidation, enabling controllable switching between antiaromatic and aromatic configurations. These results provide a compelling strategy for

• ), exceptionally high BCPL as 100.2 M−1 cm−1, and marked chiroptical activity (|gabs| = 2.50 × 10−3 at 435 nm; |glum| = 5.00 × 10−3 at 460 nm) (Table 6). Upon mild oxidation, neutral 22 undergoes stepwise conversion into highly charged, multispin open-shell species 222+2• and 224+4•, preserving strong chiroptical

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

• from esters of functionalised arylacetic acid 5 or 6 and involves two separate protocols: first, a metallacarbene, which undergoes the insertion, is generated from the corresponding diazo precursor formed either in flow via hydrazone oxidation (PS-TsNIK packed column), or in batch mode via diazo

• /RPC mechanism starts with a single-electron oxidation of the cobalt catalyst followed by a reaction with the siloxane to generate a cobalt–hydride complex. Subsequent hydride transfer to the alkene produces radical pair 23 which collapses to alkylcobalt intermediate 24. Another single-electron

• oxidation of the metal centre turns the cobalt into an excellent leaving group, allowing for an intramolecular displacement reaction that affords the oxetane ring and regenerates the Co(II) catalyst. In 2023, Silvi et al. described a versatile and practical methodology that couples Williamson etherification

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• -Alkylbenzamide constitutes the primary structural unit of this class of compounds. The structures of these compounds are relatively simple and readily synthesizable. In these photocatalytic systems, direct single-electron oxidation of the amide HRP occurs in the presence of a photoredox catalyst and a base via a

• PCET process, involving the oxidation of excited 4CzIPN* and deprotonation by a base. The resulting amidyl radical 20 smoothly abstracted a hydrogen atom from the substrate via a HAT process, generating a radical 4. This C-centered radical subsequently underwent Giese addition with activated alkenes

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

• red solid in only 4% yield. A similar strategy was used by Osborn for the synthesis of isomeric compound 6 (Scheme 1) [32]. In this case, compound 3 was dehydrogenated giving compound 4 which was then reduced to the direct precursor 5. Subsequent oxidation using chloranil yielded cyclohepta[klm]benz[e

• construction of the azulene moiety in the final step by creation of new C–C bond(s) or oxidation of a partially saturated precursor (Figure 3a); 2) The use of precursors that already contain the azulene moiety or moieties, which are then annulated into fully fused PAHs in the final step (Figure 3b). Obviously

• , the synthesis of more complex molecules may require elements of both strategies. Construction of the azulene moiety in the final step Oxidation of partially saturated precursors: With modern cross-coupling reactions providing access to larger precursors, a synthetic strategy involving the

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

• -coupling, using Cp2Fe-catalyzed electrochemical oxidation. This method leveraged the selective activation of the acidic α-C–H bond within the 1,3-dicarbonyl moiety to generate a carbon-centered radical, which was crucial for the subsequent cyclization. The reaction was carried out under reflux conditions

• . Based on these results and previous studies, a detailed reaction mechanism was proposed as shown in Scheme 12. The process begins with the oxidation of Cp2Fe at the anode to form Cp2Fe+, which then facilitates the deprotonation of the α-C–H bond of the 1,3-dicarbonyl compound by methoxide, generated at

• , affording the products 29e and 29f in quantitative yields. A plausible mechanism for the electrochemically induced radical cyclization is proposed in Scheme 16. Due to its lower oxidation potential, Cp2Fe(II) is first oxidized to Cp2Fe(III), which then oxidizes the carbanion intermediate 30 generated from

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I

• radicals and product 3 can be described by several pathways. The direct oxidation of 2 by Cu(II) A leads to the formation of P-centered radical E and Cu(I) B. Under air atmosphere, the formed Cu(I) species B can react with molecular oxygen resulting in the formation of peroxycopper intermediate C [75][76

• hydroperoxide transfer from copper complex D with the formation of intermediate H and, therefore, regenerating Cu(I) B. Alternatively, the latter can be formed by oxidation of benzylic radical G with the formation of carbocation I. However, given that in the absence of oxygen the β-ketophosphonate was formed

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

• to afford the corresponding sulfone 41. However, Uguen found that a more efficient route involved treating alcohol 40 with tosyl chloride in pyridine and DMAP, followed by nucleophilic displacement with sodium thiophenol and oxidation of the resulting sulfide with m-CPBA, yielding sulfone 41 in 85

• 94% yield. Like 40, iodination of ent-40 gave crystalline product ent-42, and its structure was confirmed by XRD crystallography. The intermediate ent-40 was then subjected to the same tosylation/thiolation/oxidation sequence used for the 40 to 41 conversion, yielding ent-41 in comparable yield (82

• , followed by oxidation with m-CPBA to provide sulfone 33, which readily was reacted with another epoxide 46b. The sequential treatments used for the condensation of ent-27 and 46a to 48a were applied to 33 and 46b, yielding the desired product 49a (77%) along with a small amount of isomeric 49b (8%). The

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• and/or audio, bringing the benefit of enhanced signal transmission (because of its high conductivity), reliability and durability (a direct result of its high resistance to oxidation) [7][8]. In medicine, gold is used as an inert and non-allergenic alternative metal in devices such as pacemakers [9

• , heat, oxidation, and hydrolysis. Owing to their properties, cyclodextrins are frequently applied in pharmaceutical formulations with low-soluble or unstable drugs [28][29][30], in cosmetic formulations [31][32], and in the food industry [33][34]. The vast majority of guests in these applications are

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