3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• under the Vilsmeier–Haack reaction conditions provided aldehyde 8 in high yield. To further assess the scope and limitations of the developed annulation protocol, we investigated the reactivity of aza-analogs of ester 1, indoles 9a‒c, toward azirine 2a under the same conditions. The reaction of N

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

• processes. It is worth noting that, in some cases, due to the high reactivity of nitrile oxides towards certain types of dipolarophiles, such as monosubstituted or activated by electron-acceptor groups olefins [31], no additional attention to this is required. However, when introducing obstructed

• benzonitrile oxides, in this case the dropwise addition method of triethylamine resulted in complete inactivity of the dipole towards the dipolarophile 2f, which was quantitatively recovered from the reaction mixture. The low reactivity of CEFNO can be explained by considering nitrile oxides in terms of

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

• [37][38]. In this context, the reactivity of enaminones under visible-light-mediated reaction conditions has attracted significant attention [39]. However, it is rather surprising that a photocatalytic approach for the synthesis of enaminones has yet to be explored. Herein, we report the first light

• enaminones. This transformation is simple, straightforward, and proceeds under mild conditions. Results and Discussion The initial challenge in achieving the desired reactivity was the activation of the unsaturated system towards the nucleophilic addition of the amine. The most common strategy to increase

• the reactivity of unsaturated esters towards an aza-Michael addition is the use of transition metal complexes as catalysts/promoters [40][41][42]. Considering this background, we reasoned that Ni(II) could be a suitable catalyst for the amination of unsaturated systems. Initial investigations were

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

• propensity (∆G° = −5.81, −5.25, and −2.55 kcal/mol for 3, 2, and 1, respectively). The protonation is more favorable in DCE (∆G° between −2.55 and −5.81 kcal/mol) than in MeCN (∆G° between −1.74 and −4.74 kcal/mol), highlighting solvent effects on reactivity. For 3 in DCE, the addition of a second MSA

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

• instances, both products were formed side by side and could be separated by chromatography. Two novel, sterically overcrowded bis-spiro(cyclopentyl) and bis-spiro(cyclohexyl)-substituted thiocarbonyl S-methanides were thermally generated from the corresponding 1,3,4-thiadiazolines and their reactivity

• 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

• chemoselectivity was observed in reactions of 1a with 5-mercaptotetrazole 4b. However, due to a lower reactivity observed for 4c,d towards 1a, the experiments with these derivatives were unsuccessful and formation of undesired side products was observed in both cases. Unexpectedly, a different chemoselectivity was

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

• –LUMO gap observed for the charged species compared to their neutral counterparts suggests enhanced reactivity and a low charge injection barrier. In the case of negatively charged FNAAP, the LUMO shifts toward the Fermi level, facilitating low electron injection. In the case of positively charged

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• Experiments, supplementary note 1). It is known that the counteranion of an iodonium salt could be a crucial factor for the reactivity pattern. Thus, we tested iodonium salts with different anions. Reactions with diphenyliodonium tetrafluoroborate 1a-BF4 (Table 1, entry 22) and tosylate 1a-TsO (Table 1, entry

• not significantly change for EWG- or EDG-substituted species except for extreme cases [44]. Additionally, such reactivity pattern cannot be explained only by steric factors since the yield dramatically dropped for o-methyl-substituted iodonium salt 1f compared to o-halo-substituted salts 1g and 1h

• (4-NO2C6H4) compared to (4-OMeC6H4) [45]. Therefore, despite the fact that literature data mostly suggest similar reactivity for aryl radicals with different substituents in the phenyl ring, the formation itself is more favorable for EWG-substituted radicals. To gain a deeper understanding of the

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

• . Additionally, using supported metals instead of metal salts can prevent the formation of chelates, which might otherwise impact the efficiency of the procedure. Moreover, this approach can provide bifunctional catalysis as the support itself contributes to the catalyst's reactivity, thus enhancing its overall

• mol % of CuCl2, an 87% product yield was obtained, while the use of CuCl enhanced reactivity, providing a nearly quantitative yield of 98% (Table 2, entries 1 and 2). When the reaction was conducted in the SynthWave reactor, pressurised with 5 bar of nitrogen, the yield of desired product dropped to

• binding to the metal, but also positively influences its reactivity. The influence of MW irradiation on reducing the reaction time was investigated using the SynthWave MW reactor, and reactions were performed under 5 bar of air to avoid the evaporation of the solvent at 80 °C, with this also potentially

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

• S18 and Figure S19 in Supporting Information File 1). Consequently, the low g values of 3 and 5 are attributable to the offset of CD signals due to the coexistence of two conformations. Reactivity The reactivity of the Wittig products was examined. Mono-olefin 3 was treated with TiCl4 and zinc powder

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

• reaction did not occur. In the presence of metal catalyst PhINTs form a nitrenoid specie, containing electrophilic nitrogen. In metal-free conditions PhINTs participates in reactions as ylide with a nucleophilic nitrogen. We expected different reactivity of the two different forms of PhINTs. However, our

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

• yields. Although the reactions do occur at ambient pressure, the pressurized reactions generally provide higher yields under the otherwise same conditions. It also appears that the reactivity of the hydrazine plays a significant role. In the case of the highly reactive hydrazine, the positive effect of

• HHP is somewhat diminished and only about 10% increase in yield was observed. In contrast, when using substituted phenylhydrazines of lower reactivity HHP results in more significant benefits, for example a nearly 70% higher yield in the case of the chalcone/3-(trifluoromethyl)phenylhydrazine reaction

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

• stable isosteric replacements for gem-dimethyl and carbonyl groups. This work reviews possible synthetic strategies towards these strained heterocycles, covering both de novo constructions of the 4-membered ring as well as derivatisations of oxetane building blocks, then reactivity of oxetanes in terms

• chemistry; natural products; oxetane; reactivity; synthesis; Introduction Oxetanes are 4-membered heterocyclic compounds containing one oxygen atom whose discovery dates back to the 1870s when the first synthesis of the parent, unsubstituted oxetane was reported by Reboul [1]. Over the next 100 years, it

• transformations of 3-oxetanone leading to advanced oxetane building blocks. In chapter 3, we review the reactivity of oxetanes with regards to ring openings and ring expansions including both symmetric and enantioselective variants. Finally, chapter 4 covers isolations, biological activities and total syntheses

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

• of amidyl radicals as HAT reagents, with a particular emphasis on their role in the intermolecular HAT process. We highlight key developments, mechanistic insights, and emerging strategies that harness the unique reactivity of amidyl radicals in the selective functionalization of a variety of

• 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

• catalytic methodology through the rational design of zwitterionic acridinium amidates. These photoactive amidyl radical precursors demonstrated exceptional HAT reactivity, enabling efficient functionalization of unactivated C–H bonds under mild irradiation conditions (Scheme 13) [98]. The mechanistic

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

• acenes from anthracene to pentacene (57a–d) in rather low yields (16–38%). The synthetic pathway leading to the hexacene isomer 60 was more complex due to the high reactivity of intermediate pentacenes. Instead, pentacene-6,13-dione 58 was subjected to the reaction with di-n-butylacetylene (56) giving

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

• , pharmaceutical development, and agrochemical production, representing one of the most significant classes of unsaturated organic compounds. Due to their broad availability and high reactivity, numerous elegant methodologies have been developed for their functionalization [1]. Among these, oxidative radical

• yields (80f,g). Perfluoroalkyl iodides, ranging from trifluoromethyl to longer perfluorinated chains, also performed well (80h). However, substrates with unprotected N–H bonds (80i) and monosubstituted olefins (80j) exhibited limited reactivity. Mechanistic investigations suggested a radical-mediated

• energy (327 kJ/mol) and is less reactive compared to alkyl bromides or iodides. Previous methodologies predominantly relied on alkyl bromides and iodides due to their lower bond dissociation energies. By leveraging the excited-state reactivity of Pd(0) complexes under blue LED irradiation, this method

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• [4.3.3]_2CHO after 1.5 h (Table 1, entry 5), which was consistent with the absence of [4.3.3]_2CHO in monoformylation. Due to the low reactivity, the reaction time was elongated to 18 h (Table 1, entry 6). The yield of [4.3.3]_2CHO was improved to 9.9%, whereas the yield of [4.3.3]_CHO decreased to 33

• ], [4.3.3]_Br and [4.3.3]_2Br. To gain insight into the different reactivity between [3.3.3] and [4.3.3], theoretical calculations were performed at the ωB97X-D/6-31G(d,p) level of theory (Figures S901–S903 in Supporting Information File 1). Although distribution of the highest occupied molecular orbitals

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• or Cl), it withdraws electron density through its inductive (−I) effect to increase diene reactivity for the cycloaddition to form 7. For example, 6l (R2 = 6-Cl, 68% yield of 8l), 6m (R2 = 6-Br, 80% yield of 8m), and 6n (R2 = 7-Br, 84% yield of 8n) are high-yielding substrates. But an electron

• thiophene to reduce the diene's reactivity or altering the electrophilicity of the dienophile. Based on the computational analysis of the transition states, reaction mechanisms for the IMDA and the dehydration re-aromatization process are proposed in Scheme 5. In the IMDA reaction for the preparation of

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

• failure may have been due to the low reactivity of sulfones 27 and ent-27 under the reaction conditions. Additionally, treating ent-42 with excess tert-butyllithium to form the corresponding lithiated derivative and reacting it with epoxide 23a, both with or without BF3·OEt2, also led to unsatisfying

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

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• only approximately 1.3 days, also has a chiral induction ability. However, improvement is required in terms of the reactivity of the catalytic reaction. Subsequently, we investigated the effect of the base using (aR)-(−)-6 by testing various bases. The reaction in the presence of Na2CO3 delivered the

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

• enamides contain an N-acyl group in place of the original alkyl group. The electron-withdrawing effect of the amide group delocalizes the nitrogen lone pair, thereby reducing the electron density and nucleophilicity of the enamide double bond. These features significantly diminish the reactivity of

• reactions [7][8], the exploration of enamides’ nucleophilic reactivity has only gained momentum in recent years. Inspired by pioneering work from various research groups [9][10][11][12][13][14][15], the potential of enamides in nucleophilic reactions has become recognized. Among them, enamide cyclizations

• the α-position of enamide to be an active cyclization site, with the alkyne tether acting as the nucleophile. Since it is well-established that alkynes, when activated by transition metals such as gold or platinum, can also function as electrophiles, modulating the reactivity of the decahydroquinoline

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• publications [19][23][24] confirmed the structure with IR and MS data, or by reactivity. Herein, we report the full set of assigned 1H and 13C NMR data for both the base and the dihydrochloride salt. In the course of our efforts devoted to elaborating a new and efficient synthesis of brevicarine (2), we

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

• Abstract We present the first examples of alkene amino-sulfonoxylation reactions that leverage the unique reactivity of carbamate tethered N-alkoxy nitrenium ions. In almost all cases examined, the reactions deliver product with exquisite regioselectivity and diastereoselectivity. The protocols followed

• single regioisomer and diastereomer of B was formed (within the limits of 1H NMR detection), attesting to very selective reactivity. Here and in related projects, we found that many I(III) sources could generate a nitrenium ion, including iodosobenzene (PhIO) and iodomesitylene diacetate. However, unless

• new alkene amino-sulfonoxylation reaction that leverages the unique reactivity of carbamate tethered N-alkoxy nitrenium ions. In almost all cases examined, the reactions delivered product with exquisite regioselectivity and diastereoselectivity. The protocols followed were operationally very simple

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

• diverse scaffolds have been reported in the literature, the identification and use of novel PCs with tunable and diverse optical and redox properties can pave the way to uncharted reactivity. In this context, sulfur-based cores, widely used as acceptors in photoelectric materials [9][10][11][12][13][14

• ). Giese addition using N-Cbz-Pro (12) and dimethyl maleate (13). Pinacol coupling of benzaldehyde (15). Supporting Information Supporting Information File 10: Reactivity studies, general experimental procedures, product isolation and characterization, spectroscopic data for new compounds, and copies of

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

• reactivity of those two alcohols toward oxidation allowed for the selective conversion of desired alcohol to ketone 24 using PCC, producing a 50% overall yield, while the recovered undesired alcohol could be reverted to 21 by Swern oxidation. Direct enol triflation (Et3N/Tf2O, NaH/PhNTf2, DTBMP/Tf2O, etc