Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• ). (c) Simulated absorption spectra of these compounds (B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d,p) level of theory), and (d) molecular orbitals mainly contributing to the optical transitions indicated by arrows. Emission decay curves of Pe–PTZ(TPA)2 in benzene excited at 403 nm and probed at 460 and 632 nm

• (a, c) 350 nm (20 nJ/pulse) and (b, d) 420 nm (6 nJ/pulse) at room temperature. (a) Femtosecond-to-nanosecond transient absorption spectra and (b) evolution-associated spectra (EAS) of Pe–Ph–PTZ(TPA)2 in benzene excited at 350 nm (20 nJ/pulse) at room temperature. Summarized photophysical process of

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• advances require expanding the range of pH-responsive systems and discovering new molecular architectures. Here, we investigate the pH-responsive behavior of ortho-disubstituted benzamidine, which generates atropisomers and E/Z isomers. The amidine moiety allows modulation of the C–N and C–N/C–C rotational

• barriers by protonation, providing a novel approach to control the kinetics of isomerization via pH adjustment. The results showed that protonation of the amidine moiety significantly suppresses both C–N bond rotation and C–N/C–C concerted rotation, demonstrating the potential of ortho-disubstituted

• switches [19]. For example, hydrazone-based molecular switches undergo reversible E/Z isomerization around the C=N bond [1][2][3][4][5][6][7], with protonation significantly shifting the equilibrium. Beyond double-bond isomerization, pH stimuli have also been employed to modulate rotational barriers in

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , respectively [19][20]. Recently, our group established an efficient synthetic strategy for strained macrocyclic polyarenes, such as compound C, in which o-phenylene units preorganize adjacent heteroaromatics into close proximity, thereby facilitating oxidative ring-closure reactions [21]. Among these, the

• macrocycle whose structure has been confirmed by X-ray diffraction analysis. Next, oxidation of 4 was attempted using [bis(trifluoroacetoxy)iodo]benzene (PIFA) in CH2Cl2 at −78 °C (Scheme 2). These reaction conditions had previously proven effective for the oxidation of 3 and other o-phenylene-bridged

• acyclic heteroaromatics [26][27]. Thus, to a solution of 4 in CH2Cl2 was added 15 equivalents of PIFA at −78 °C and stirred for 3 h. The mixture was then allowed to warm to room temperature to give a dark solution. The system was worked-up with NaBH4/MeOH for 10 minutes followed by extraction with CH2Cl2

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• Federation, 115478, Moscow, Russian Federation 10.3762/bjoc.21.118 Abstract The cycloaddition of 1,3-dipoles at C=N bonds is a relatively rare process, in contrast to the widespread cycloaddition reactions at C=C, C≡C, and C=S bonds. In this study, we present the syntheses of novel hydantoin/1,2,4

• -oxadiazoline spiro-compounds using a 1,3-dipolar cycloaddition of nitrile oxides to C=N bonds of 5-iminohydantoins. The efficiency of the approach was demonstrated by varying the substituents at four positions of the resulting spirocyclic molecules. Cytotoxicity of the target hydantoin/1,2,4-oxadiazolines was

• of double and triple bonds, most of the described reactions are related to dipolarophiles with C=C, C≡C or C=S bonds [7]. However, the [3 + 2]-cycloaddition of nitrile oxides to exocyclic C=N bonds, is a much less explored area. There are few known reactions of these dipoles with imino derivatives of

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• it is negative in the Ames test [25]. Recently, we determined key physicochemical properties of CyreneTM and showed that it has a negligible vapor pressure (<9.6 kPa) and low viscosity (<6.8 mPa·s) at typical transition-metal-catalyzed reaction temperatures (30–140 °C) [26]. CyreneTM has been

• , a wide range of organic reactions, e.g., urea and amide formation [32][33], amide coupling [34], aldol condensation [35], C–H difluoromethylation [36], aromatic substitution [37], and MOFs synthesis [38] were demonstrated in CyreneTM. Very recently, Fasano and Citarella first reported a CuAAC

• ) were tested in the conversion of 1.15 mmol benzyl azide (1a) and 1 mmol phenylacetylene (2a) in 2.5 mL CyreneTM at 30 °C. All the selected Cu salts catalyzed the cycloaddition; however, Cu chlorides and oxides resulted in unexpectedly low product yields after 0.5 h. The solubility of Cu oxides was

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• -dimethylformamide (DMF) at 20 °C afforded the best results, giving the desired product 9a in 70% isolated yield (Table 1, entry 1). Changing NiBr2·diglyme to other nickel salts, such as Ni(OTf)2 and NiCl2·diglyme led to lower yields (Table 1, entries 2 and 3). Similarly, changing the ligand for dtbbpy or

• . Simultaneously, acridinium photocatalyst PC1 absorbed energy and transitioned from the ground state to excited state under visible-light irradiation. This excited state PC1* is quenched by the amine, generating the amine radical cation and PC1 radical via a single-electron transfer (SET) process. Then, the C−Br

• bond of I is cleaved by PC1•, generating a C-centered radical II, which can be further reduced to give an enolate III, that ultimately evolves to the more stable anion IV and undergoes protonation to afford the final enaminone product 9a. Conclusion In summary, a simple and effective nickel-assisted

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• is assumed. Stronger electron donation gives rise to larger red-shift, and hence more pronounced color changes, upon protonation, as illustrated in Figure 1C. Figure 1D illustrates the shift in protonation equilibrium with increasing acidity when MSA is added to DCE solution of 3 at 25 °C. Due to the

• with 1.44 mM MSA over a 10–80 °C temperature range. Comparing the maximum absorbances at the neutral and protonated peaks provides a measure of sensitivity and optimal working range. Figure 2B presents this comparison for 1–3 in MSA/DCE solutions, calculated as the ratio between neutral and protonated

• , the rate of change should be both high and systematic. For example, in Figure 2B, the optimal range for 3 appears to be between 30 and 80 °C, where the rate of change is fastest and follows a clean, exponential trend. All three compounds show similar sensitivity in DCE, while the sensitivity of 3 is

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• acetylene production, was investigated. The catalyst was obtained by calcination of calcium carbide slag at 600 °C (CS600) and characterized by XRD and FTIR analysis. The transesterification reactions were carried out with primary alcohols, producing fatty acid alkyl esters in 51–99% yields, depending on

• was calcined at 600 °C before use and the catalyst CS600 was characterized using XRD and FTIR analysis, confirming the presence of CaO as the main phase. The primary alcohols successfully reacted in the transesterification reaction to give the corresponding fatty acid alkyl ester mixtures in yields

• fine organic synthesis. Results and Discussion The carbide slag was prepared by hydrolysis of commercially available calcium carbide (Sigma-Aldrich) and oven dried at 80 °C for 3 hours. The active catalyst CS600 was prepared by calcining the carbide slag at 600 °C for 2 hours. The composition of the

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• five-membered heterocycles via [3 + 2]-cycloaddition reactions. Depending on the type of the dipolarophile used in these reactions, the target heterocycles may contain only one sulfur atom (cycloadditions with C=C or C≡C dipolarophiles) or more heteroatoms (cycloadditions with C=S, C=O, C=N, N=N, S=O

• sulfur (χ = 2.55 (for C) and χ = 2.58 (for S) according to the Pauling scale), thiocarbonyl S-methanides 1 are considered as electron-rich 1,3-dipoles with basic and nucleophilic reactivity displayed by the =S+–CH2‒ unit [6]. Therefore, acidic compounds of type R–XH (X = NR’, O, S), which are able to

• ], were analogously treated with CH2N2 at ca. 0 °C and the expected cycloadducts 2c and 2d were formed with complete regioselectivity, and subsequently could be isolated in good yields without a remarkable decomposition (Scheme 3). Thermal decomposition of 2a and 2b, and the behavior of the corresponding

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• intermediates. (c) All 8 states are accessible reversibly even at lower sample voltages, indicating that switching can be performed between any given state at a low threshold voltage. That is, all states are accessible and are remarkably stable at all sample voltages. It is concluded that the high energy

• pyrolytic graphite (HOPG, ZYB grade from μMasch). Approximately 4 μL of solutions of FNAAP were drop-casted on the HOPG surface, dried (a few minutes) in ambient conditions, and AFM/STM studies were performed. Relative humidity (≈50%) and temperature (22–25 °C) of the room were controlled by an air

• conditioner and a dehumidifier. While drop casting, the sample was kept at ≈20–30 °C to ensure a smooth flow of the solvent over the substrate. After drop casting, all films were subjected to vacuum pumping (typically 0.01 mbar) for about 1 h. Before depositing molecules, freshly cleaved graphite surfaces

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• ][23][24][25][26]. Most of these synthetic approaches rely on similar strategies, i.e., coupling of the A ring and the C ring followed by the formation of the B ring. Additionally, the semisynthesis of analogues of 1 has been reported and led to the discovery of ISIR-050 (4), which shows higher

• activity than cotylenin A in cell growth inhibition assays and less toxicity in single-agent treatments [27][28]. Recently, Jiang and Renata described a chemoenzymatic approach that combines the skeletal construction by chemical methods and enzymatic C–H oxidations [29]. The synthesis employs a catalytic

• Nozaki–Hiyama–Kishi reaction and a one-pot Prins cyclization/transannular hydride transfer to construct the 5-8-5 tricyclic scaffold. Enzymatic oxidations were used to install the hydroxy group at the C-3 position. Ten fusicoccanes were synthesized in 8–13 steps each. Despite these efforts, a strategy

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• straightforward reactions. Complementarily, the Review article by Jang and Kim provides a deep understanding of recent advances in the combination of electrochemistry and copper catalysis for various organic transformations [3]. Their contribution elaborates various C–H functionalizations, olefin additions

• , decarboxylative functionalizations, and Chan–Lam coupling reactions. In doing so, the authors point out the combination of transition-metal catalysis and electrochemistry as an efficient, sustainable method for the oftentimes challenging formation of C–C and C–heteroatom bonds in complex molecules. Another Review

• -workers demonstrates that the efficient and green direct C–H amination of benzoxazoles can be catalyzed by copper chloride salts in acetonitrile in the absence of any acidic, basic, or oxidizing additives [8]. Both CuCl and CuCl2 were found to be extremely efficient in promoting the reactions, which

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

• , and the huge overall economic impact of these processes. Inspired by the logic behind cross-dehydrogenative C–C-coupling methods [15], the direct C–H amination has been developed as a more straightforward, economical and environmentally friendly reaction, compared to its counterparts (such as the

• classical Buchwald–Hartwig amination reaction [16] or the Ullman reaction [17][18]) which require pre-functionalisation steps and harsh conditions [19]. Many protocols for C–H aminations have been applied to heteroaromatic compounds, mainly 5-membered heteroarenes, and a great deal of attention has been

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

• ruled out. The structures of compounds 3, 4, and 5 were determined by X-ray diffraction analysis (Figure 2). Mono-olefin 3 and bis-olefin 5 adopt a bathtub-like chiral macrocyclic structure rather than figure-eight conformation. Both compounds crystallize as a racemic pair of enantiomers with P21/c and

• low racemization barrier as with structurally similar methylenedioxy-substituted DBC derivative [22]. Racemization dynamics The racemization barriers of CBBC 1, mono-olefin 3, and bis-olefin 5 were evaluated by monitoring the decrease of circular dichroism (CD) signals in 1,2-dichlorobenzene at 170 °C

• conformation (Sa,Sa)-A is feasible with a small activation barrier of 9.9 kcal mol−1. The figure-eight conformer (M,M)-B untwists to adopt an achiral conformation C with the exo-alkene units rotated inwards in opposite directions. These conformational changes are almost identical to those of CBBC 1. However

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

• 2a–c featuring a nitrogen-embedded cyclopenta[ef]heptalene core [15]. These compounds exhibit λabs at 363, 452, and 580 nm, and PLQYs of 0.05, 0.33, and 0.32, respectively. While compounds 2a and 2b display broad emission near 505 nm, 2c shows dual-emission peaks at 588 and 634 nm with an ultranarrow

• extending into the near-infrared region, suggesting potential for redox-responsive chiral photonic systems. In 2023, Chen’s group reported three nitrogen–nitrogen (NN)-embedded azahelicenes 21a–c, among which compound 21c, a structurally defined antiaromatic double aza[7]helicene – exhibited distinctive

• , thereby advancing their application in multifunctional chiral photonic and sensing platforms. In 2025, Gryko’s group synthesized a series of heterohelicenes 34a–c, featuring a 1,4-dihydropyrrolo[3,2-b]pyrrole (DHPP) core [48] (Table 10). The compounds exhibit similar absorption and emission profiles

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• E/Z isomerization around the C=N bond leads to reduced efficiency of the tautomeric based switching [52]. In this respect, based on the excellent stability of the azo compounds, it is interesting to understand the effect of the competitive proton transfer and E/Z switching by replacement of the

• reasons are different. While in acetonitrile this is the effect of the increased polarity of the solvent, leading to stabilization of the more polar keto tautomers, in the non-polar chloroform it is caused by its proton-donative nature (formation of a stabilizing intermolecular hydrogen bonding with the C

• equilibrium towards C=O-group-containing structures. In addition, the spectra in the remaining solvents show a single band around 500 nm independent on the nature of the solvent. Obviously, these data cannot be interpreted in the frame of the concept for a tautomeric equilibrium. The rotor in 2 contains a OH

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• as a model for searching the optimal synthesis conditions (Table 1). We found that when processing thioamide 1a with PhINTs (2a, 1.5 equiv) in chloroform at 50 °C in the presence of Rh2(Piv)4 (0.5 equiv), 2,3-dihydro-N-sulfonyl-1,2-thiazole 3aa is formed with a 48% yield (Table 1, entry 1). When

• larger or even commercial scale. The structures of compounds 3 were confirmed by 1H and 13C NMR spectroscopy and high-resolution mass spectrometry. The 1H NMR spectra are characterized by signals from protons of the aromatic rings in the range of 8.08–7.32 ppm, singlets for the proton at the C-3 position

• of the 2,3-dihydro-1,2-thiazole ring in the range of 6.44–6.06 ppm, and multiplets corresponding to the morpholine fragment in the range of 3.80–2.89 ppm or protons of residues of other amino groups in the range of 3.51–1.31 ppm. In the 13C NMR spectra, characteristic signals of the C-4 atom of the

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• in the soil and thereby inhibiting the growth and sporulation of several pathogenic microorganisms [14]. In our effort to discover new bioactive secondary metabolites, our group previously cultured the Pseudomonas UIAU-6B strain in a closed system at 28 °C, and the methanolic extract led to the

• isolation of five phenolic siderophores with some of them exhibiting antimicrobial properties, including pseudomonins A–C and pseudomobactins A and B [15]. In this study we report the isolation and structural characterization of two previously undescribed as natural products (1 and 2) and two new compounds

• File 1, Figures S1–S4) of 1 measured in deuterated DMSO revealed well-defined proton signals identified as four aromatic sp2 methines, two aliphatic sp3 methines, a methyl group and four quaternary carbon signals at δC 157.7 (C-1), δC117.8 (C-6), δC 167.2 (C-7), and δC 172.9 (C-10). The presence of a

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• of catalyst- and solvent-free processes is desirable. Chalcones are a privileged scaffold in medicinal chemistry and are used for the synthesis of a multitude of products [43]. The cyclization between chalcones and hydrazines usually occur via a C=O/NH2 condensation and a subsequent NH addition to

• the C–C double bond, that most commonly require some form of catalysis. Thus, developing catalyst-free processes presents significant challenges, although there are few successful examples in the literature [44]. Similar to the dihydrobenzimidazoles above, the investigations here also started with an

• parentheses. As shown in Table 4 and Scheme 4, the HHP reactions occurred at 50 °C with low to moderate yields, and with nearly quantitative yields at 80 °C. HHP reactions afforded the products in higher yields than those of the control experiments under the same conditions (time, temp. etc.) but only at 1

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

• tetrahedral value which results in a large ring strain of 25.5 kcal/mol, comparable to oxirane (27.3 kcal/mol) and much greater than tetrahydrofuran (5.6 kcal/mol) [4]. Moreover, the strained C–O–C bond angle effectively exposes the oxygen lone pairs, making oxetane a strong hydrogen-bond acceptor and Lewis

• E [30] and daphnepapytone C [31] from the 2020s (Figure 4). Most of these compounds possess intriguing biological activities and selected examples from this list are discussed in more detail in chapter 4 with regards to their isolation, bioactivity and a recent total synthesis. The aim of this work

• categorised into 6 synthetic strategies as depicted in Scheme 1: a) C–O bond-forming cyclisations, b) C–C bond-forming cyclisations, c) [2 + 2] cycloadditions between carbonyls and alkenes, d) ring expansions, e) ring contractions and f) O–H insertions. In the following subchapters, these strategies will be

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

• transfer (HAT) in photocatalytic reactions. These radicals display exceptional selectivity and efficiency in abstracting hydrogen atoms from C–H, Si–H, B–H, and Ge–H, positioning them as invaluable tools in synthetic chemistry. This review summarizes the latest advancements in the photocatalyzed generation

• substrates. Keywords: amidyl radicals; C–H; HAT reagents; hydrogen-atom-transfer; late-stage functionalization; Introduction C–H bonds are the predominant chemical bonds in organic compounds, and their direct conversion can rapidly and efficiently increase the complexity and functionality of organic

• molecules. On the other hand, C–H bonds exhibit low reactivity due to their relatively high bond dissociation energy (BDE) (Figure 1a). Therefore, the direct functionalization of C–H bonds is extremely challenging [1][2][3][4][5]. In recent decades, transition-metal-catalyzed C–H bond functionalization

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

• synthesis of π-extended azulene was the non-benzenoid isomer of pyrene published by Ward and co-workers (Scheme 1) [31]. Cyclohept[bc]acenaphthylene (2) was obtained from a partially saturated precursor 1 via dehydrogenation using palladium on carbon. However, the reaction carried out at 300 °C gave 2 as a

• dehydrogenated using sulfur in trichlorobenzene at 220 °C to yield the azulene-containing isomer of benzo[a]pyrene 9 in 18% isolated yield. Bestmann and Ruppert reported the synthesis of a dinaphthoazulene 14, a non-alternant isomer of benzo[a]perylene (Scheme 2) [34]. In their method, bisylide 10 was reacted

• by Jutz and Kirchlechner in 1966 (Scheme 3) [36]. Condensation between phenalene 15 and pentafulvene 16 gave pentafulvene 17. Pentafulvene 17 was finally subjected to Ziegler–Hafner reaction in quinoline at 180 °C, resulting in the π-extended azulene 18 in 60% yield. A similar synthetic strategy was

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

• transformations, (4) electrochemical approaches, and (5) metal-free or electron donor–acceptor (EDA)-driven systems. The substrate scope, limitations, and mechanistic aspects of these radical cascade cyclization strategies are critically examined. Review N-Arylalkenes: alkyl C(sp3)–H radicals Early investigations

• primarily focused on substrates containing activated alkenes tethered within the molecular framework. N-Arylacrylamides were employed as model substrates, and a diverse range of functionalization reagents, including those with benzylic C–H bonds, C(sp3)–H bonds adjacent to heteroatoms, di

• 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

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• . This can be obtained from renewable biomass and is therefore considered to be a "green" solvent. In 2-MeTHF (conditions (C)), product 1f was isolated with a yield of 95% and derivative 1h with a yield of 91%. This shows that the sustainable solvent is a potent alternative to 1,4-dioxane. With the new

• ® and purified by flash chromatography on silica gel (n-hexane/acetone 3:1). Then, the crude product was suspended in n-hexane, the supernatant separated by filtration and the precipitate was dried under vacuum to afford aroyl-S,N-ketene acetal 1i (1.78 g, 4.93 mmol, 99%) as a yellow solid. Mp 159 °C

• (lit. 155 °C [5]). 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 6.43 (s, 1H), 6.92–7.04 (m, 3H), 7.09–7.16 (m, 3H), 7.19–7.29 (m, 4H), 7.57 (dd, 3J = 7.7 Hz, 4J = 1.3 Hz, 1H), 7.73–7.83 (m, 2H); MALDI–TOF–MS (m/z): 362.2, [C22H16FNOS + H]+. Retrosynthetic analysis of aroyl-S,N-ketene acetals 1 and tentative

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

• ) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert. Keywords: C–P coupling; copper; enol acetates; β-ketophosphonates; phosphorylation; Introduction The construction of C–P bonds is a highly important task in key areas of modern chemistry

• efficiency, strong basic or acidic conditions, and excess of organohalides as starting materials. Recent years have witnessed the upsurge of free-radical oxidative phosphorylation transformations that became a reliable strategy for the construction of C–P bonds in organophosphorus chemistry [2][32][33][34

• leading to β-ketophosphonates have been reported [41][42][43][44][45][46][47][48][49][50][61], challenges in this area still exist primely in the search for new available synthetic equivalents of alkynes and alkenes for effective radical C–P bond formation. Enol acetates are potentially versatile