Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• presence of NHC (20 mol %), 4CzIPN (2 mol %) under mild conditions, producing corresponding unsymmetrical ketone derivatives 8 in up to 95% yield. An Ir-based photocatalyst was initially selected because its excited state is a strong oxidant (E1/2[Ir*III/II] = +1.21 V). Although 4-ethylanisole exhibits a

• /organophotocatalyzed oxidative Smiles rearrangement of O-aryl aldehydes 26 has been developed using oxygen as the terminal oxidant under visible-light dual catalysis. This approach afforded highly functionalized 2-hydroxyarylbenzoates 27, tolerating electron-deficient and electron-rich substituents. The C–O bond

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• ]dec-5-ene)-catalyzed intramolecular aldol reaction connected C6 and C8, assembling the trans-pentalene ring and affording the core carbon framework of illisimonin A. The C1 hydroxy group was initially introduced by a Mukaiyama hydration reaction using O2 as the stoichiometric oxidant; however

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• and copper salts were examined as an oxidant to enhance the yield. Surprisingly, none of the tested silver salts afforded the desired product, while copper salts resulted in either trace amounts or a lower yield of 2a (Table 1, entries 4 and 5). We also evaluated inorganic oxidants, but these oxidants

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• of alkenyl halides 7a and 7b with the green oxidant H2O2 gave trace conversion after 3 days; however, the reaction using m-CPBA catalyzed with p-TSA was complete in 24 hours and afforded the halogenated lactones 8a and 8b in 33% and 34% yield, respectively (Scheme 1). We have recently reported the C3

• epoxidations of 5 are highly stereoselective [44]. Unambiguous assignment of configuration for the diastereomers was not possible on the basis of the selective 1D NOE spectra due to the lack of informative crosspeaks. Limiting the amount of oxidant (H2O2 or peracetic acid) resulted in mixtures, suggesting that

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• applied in the development of enantioselective polyene cyclizations, which demonstrated the power of the catalytic strategy. In the presence of a chiral amine catalyst 16 (Scheme 3) and the mild oxidant Cu(OTf)2, polyenes with a terminal aldehyde group underwent intramolecular cyclizations affording

• chemical oxidant or reductant [80][85], thereby reducing toxicity and waste. With these advantages, organic electrochemistry holds significant promise for improving efficiency and sustainability while enabling the development of new transformations. Meggers and co-workers developed an electrochemical

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• as an oxidant, combined with NaH as the base, increased the formation of 3a, achieving GC yields of up to 65% (Table 1, entry 3). Control experiments demonstrated that palladium, phosphine, and base were all essential for this reaction (Table S4 in Supporting Information File 1). However, under

• addition of 2 equivalents of water (Table 1, entries 12 and 13). Finally, the oxidant t-Bu-OO-t-Bu could be replaced by O2, yielding compound 3a with GC yields of up to 79% (Table 1, entry 14, 75% isolated yield). In reactions giving <70% isolated yield, no single side-product dominates; the missing mass

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• -metal catalyst and oxidant, was an economic and efficient protocol compared with the previous method [174][175][176][177][178][179][180][181][182][183][184]. The ruthenium-accelerated electrochemical dehydrogenative annulation of alkyne with an aniline derivative was also an efficient method to build

• , oxidant, and base-free conditions. An electrochemical enantioselective tandem C–H indolization of 2-alkynylanilines with 3-functionalized indoles towards 2,3′-biindolyl atropisomers was achieved by Zeng in 2025 (Scheme 7) [204]. After screening the reaction carefully, the optimal conditions were gained as

• nucleophilic substitution of D afforded target indeno[1,2-c]pyrrole 40a along with eliminating I. Notably, this oxidant-free and catalyst-free approach could be potentially applied in the pharmaceutical manufacture. A Rh-promoted synthesis of pyrroles through annulation of alkynes and enamides was demonstrated

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

• a C1 building block for the N-formylation of secondary amines to formamides under catalyst-free conditions and air as oxidant. This method was applied to different aromatic and aliphatic (both cyclic and acyclic) amines (Scheme 3) [31]. Already in 1955, Parham and Reiff reported the synthesis and

• simulated solar light and molecular O2 as the oxidant, and mesoporous carbon nitride (SGCN) as the photocatalyst. The latter showed excellent photoconversion (>95%) of furfural with 33% and 42% selectivity of HFO and MAN, respectively (Scheme 35). Xiao et al. developed this method and suggested that the

• Fe2B2 can be used as electrocatalyst for the production of furanoic acid and HFO with potentials of −0.15 V and −0.93 V, respectively [117]. Chavan et al. reported a simple and efficient method for the synthesis of HFO from furan by using oxone as oxidant (Scheme 36a) [118]. Before this study Kumar et

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• transformation was successfully achieved by using PhI(OAc)2 as oxidant, providing 7-O-demethylmonocerin, containing the cis-substituted THF ring with sole diastereoselectivity. Site-selective mono-methylation gave rise to monocerin. The bioinspired approach successfully found applications in the total synthesis

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• transition-metal-mediated oxidative radical cyclization for constructing cyclopentanone 14. First, we used Mn(OAc)3·2H2O/Cu(OAc)2·H2O [21] as the oxidant system to perform oxidative annulation of β-keto ester 15 in MeCN as solvent. However, only 9% of the desired product 14 was obtained after conducting the

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• good yield and excellent enantioselectivity (Scheme 5). Notably, two distinct oxidative aromatization methods have been developed to yield diverse heterohelicene products. For instance, using DDQ as an oxidant selectively delivered hetero[7]helicenes 19 with monoamido substitution at the peri-positions

• , while utilizing MnO2 as an oxidant selectively yielded heterohelicenes 20 with bisamido substitution at the peri-positions. In 2024, Zhou, Chen and co-workers disclosed an efficient method for the asymmetric synthesis of indolohelicenoids through a sequential enantioselective annulation, followed by an

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• features of this protocol include the use of O2 as an ideal, green oxidant, operational simplicity and scalability, high atom- and step-economy, and cost-effectiveness, collectively enabling the single-step synthesis of two medicinally relevant N-heterocycles in excellent combined yields. Keywords: C–C

• biocatalysts, as well as enzymatic processes. Among these, molecular oxygen stands out as a greener and more sustainable oxidant due to its natural abundance, low cost, and environmentally friendly properties, making it an appealing option for both academic research and industrial applications. Recently, some

• [53]. In this work, the authors used a stoichiometric amount of Zn(OTf)3 as a Lewis acid catalyst and air as the oxidant for the reaction. Jana and colleagues demonstrated an atom-efficient pseudo-three-component C–H annulation reaction catalyzed by Yb and Cu, which involved nitrosoarenes and styrene

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

• the material [70]. Oxygen balance (OB), a critical parameter quantifying how well an explosive provides its own oxidant, reveals potential safety risks when OB values exceed the threshold of −200. Since the energy release predominantly originates from oxidation reactions, the available oxygen content

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• ) transition, resulting in a long-lived charge-separated species. In this excited state, [Ru(bpy)3]Cl2 is both a more potent oxidant and reductant than in its ground state. This reactivity, in combination with the reversible redox behavior of the metal complex, enables reductive or oxidative quenching cycles

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• target Heck coupling, finding that using 1,4-dioxane as the solvent and 20 mol % PdCl2 as the catalyst, 11 could be obtained in 40% yield in the air. We tried by using more catalyst, or adding O2 (or CuCl2) as oxidant, but all these efforts did not give improved reaction yields (the reason for this was

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

• offers wide-ranging potential for substrate expansion and the functionalisation of bioactive compounds. This study presents a green and efficient C–H amination, catalysed by CuCl and CuCl2, in acetonitrile without acidic, basic or oxidant additives that is accelerated by microwave (MW) irradiation and is

• oxidant considerably impacts upon the sustainability of the process because it involves toxic reagents, generates hazardous by-products, increases the overall reaction cost and increases waste production [30][31][32]. In subsequent years, other base-catalysed protocols have been developed for the reaction

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• dibenzo[g,p]chrysene (DBC, 2) via oxidative inner-bond cleavage (Figure 1) [16][17]. CBBC 1 was first synthesized by Suszko and Schillak in 1934 using sodium dichromate as an oxidant [16]. Recently, our group developed a scalable, catalytic, and enantioselective protocol to furnish CBBC 1 [17]. Several

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

• stimuli-responsive chiral electrochromic materials. In the same year, You’s group developed a transition-metal-catalyzed C–H/C–H-type regioselective C3-arylation of benzothiophenes using molecular oxygen as the oxidant [79]. This strategy afforded the TADF-active compound 64a, which exhibits efficient

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

• 27 [43] which first yields the partially saturated product of the Scholl reaction (28) when FeCl3 in CH2Cl2/MeNO2 was used as an oxidant. Further oxidation was possible using DDQ in 1,4-dioxane and finally fully unsaturated PAH 29 was isolated in 87% yield. Compound 29 is a substructure of PAH 26 but

• using FeCl3 as the oxidant (Scheme 14) [70]. The use of K2CO3 as an additional base was necessary because residual moisture, in the presence of FeCl3, led to the protonation of the starting azulenes. Interestingly, when azulenes were substituted exclusively with phenyl groups, no desired product was

• ]. Notably, PAH 109 forms an air-stable radical cation after oxidation. A similar intramolecular oxidation of two adjacent azulene units was also reported with the use of FeCl3 as an oxidant [73] or in one step during Suzuki coupling between 1,8-dibromonaphthalene and borylated azulene [74]. The ease of

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

• activated alkenes involving benzylic C(sp3)–H bonds through a cascade cyclization process (Scheme 1) [2]. This organomediated approach can be facilitated by a catalytic amount of Lewis acid. Using DTBP as the oxidant and IrCl3 as the promoter, a range of benzylic C–H bonds in arylmethanes

• heteroatom for the synthesis of functionalized oxindoles was also reported in 2013 [3]. In this study, DBU was employed as a ligand and TBHP as an oxidant. A series of ethers, including 1,2-dimethoxyethane, THF, 1,4-dioxane, tetrahydro-2H-pyran, 2,3-dihydrobenzofuran, tetrahydro-2H-thiopyran, and N

• equimolar amount of tert-butyl hydroperoxide (TBHP) as the oxidant, with the reaction conducted at 100 °C under an argon atmosphere, resulting in a 79% yield of the desired product 7a without the requirement for any metal catalyst. In terms of substrate scope, the study explored various N-arylacrylamides

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

• reactions leading to the corresponding unfunctionalized carbonyl compounds. To date, only the Xu group reported oxidative phosphorylation of enol acetates with dialkyl H-phosphonates and Mn(acac)3 as an oxidant (Scheme 1b) [71]. However, the reported approach is limited by an excess of manganese salt, long

• reaction times, and scope limitations. In the present work, the selective copper(II)-mediated phosphorylation of enol acetates with the formation of substituted β-ketophosphonates employing cheap copper sulfate as a catalyst and atmospheric oxygen as a terminal oxidant was carried out (Scheme 1c). Results

• oxide gave the corresponding product 3s in 58% yield, although earlier 3s wasn’t observed in an analogous reaction when Mn(acac)3 was used as an oxidant [71]. The synthetic utility of the developed protocol was demonstrated by performing the model reaction on a 6 mmol scale (Scheme 3), product 3a was

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

• -workers (2023) employed a Cu(II) square-planar complex {[CuIIL] LH2, 9,9’-(ethane-1,2-diylbis(azanediyl))bis(1H-phenalen-1-one} to convert cinnamaldehyde (162) into methyl cinnamate (44) in the presence of H2O2 as green oxidant via intermediate 164 formation (Scheme 52B) [93]. Using a different earth

• reactions, have also been explored, thus boosting sustainability value. For instance, Wang and co-workers (2019) synthesized benzyl cinnamate (166) from cinnamaldehyde (162) catalyzed by an NHC catalyst (cat 4) in the presence of the low-cost oxidant CCl3CN. The reaction involves formation of acyl azolium

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

• ring was opened in a diastereoselective (SN2 type) and exo-selective manner by a trifluoroacetate anion. The trifluoroacetate anion was conveniently derived from (bis(trifluoroacetoxy)iodo)benzene (PIFA), which was used as the stoichiometric oxidant in the reaction. Overall, this amounted to a highly

• disulfonoxylation [2] and alkene amino-trifluoroacetoxylation [4], we hypothesized that treatment of (E)-hex-3-en-1-yl methoxycarbamate with a mixture of an I(III) oxidant and a sulfonic acid would lead to the formation of amino-sulfonoxylated product. We were thus very pleased to observe 59% of desired product B

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

• derivatives of glycine with diarylphosphine oxide (R2P(O)–H) for the synthesis of 1-aminoalkylphosphine oxides without the use of any transition metal catalyst or external oxidant. In this conversion, 1-aminoalkylphosphine oxides were formed in an undivided cell using a carbon electrode as the anode and

• electrochemical method. They have synthesized 30 different thiazole phosphine oxides with up to 91% yield at room temperature without using an external metal or oxidant. The reaction was carried out in an undivided cell using glassy carbon as the anode and foamed copper as the cathode electrodes at a constant

• process for synthesizing π-conjugated phosphonium salts at room temperature in catalyst/oxidant-free conditions. The reaction was carried out in an undivided cell using a platinum plate as the anode and platinum wire as the cathode at a constant current of 4 mA. The reaction proceeded via an anodic

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

• (CuCl2, NaNO2, TEMPO) using molecular oxygen as a terminal oxidant have also been used [12]. Nevertheless, neither of these conditions was successful when they were applied to methanol to generate formaldehyde, because overoxidation is an important side reaction in these cases [12][13][14][15]. However

• ). Additionally, the Tiwari group developed a metal-free protocol using only K2S2O8 as an oxidant for the activation of DMSO to MMS (Scheme 8, path II) [38]. Under these conditions, an alternative mechanism arises in which the imine intermediate B, formed as previously stated through reaction between the aniline

• to the resulting compounds. Once again, DMSO was confirmed as the origin of the methylene bridge by isotope labelling experiments using DMSO-d6. The proposed mechanism comprises the activation of DMSO by a Ru(III) catalyst and the role of Selectfluor working as the oxidant that allows the "activation