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

• alcohols 13 and a binary Al/TBAB catalyst (Scheme 5) [40]. The reaction is carried out in toluene upon mild heating, providing the bicyclic products in high to excellent yields. Both electron-rich and electron-poor phenyls as well as aliphatic chains worked well, however, increased temperature and catalyst

• under mildly basic conditions to prevent possible side-reactions, specifically iododesilylation and oxetane opening by the relatively nucleophilic succinimide. Attempts to prepare the bulkier 2,3,3,4,4-pentasubstitued oxetanes were unsuccessful due to very poor conversions (<5%) and heating those

• , anhydrous conditions and mild heating to afford the products in moderate to good yields. The reaction worked well for both aliphatic and aryl-substituted substrates but best results were obtained for shorter hydrocarbon side chains and 2,6-disubstituted phenyls. The authors demonstrated the applicability of

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

• insight in the development of novel methods for amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer. Although, amidyl radicals employed in many reactions as HAT reagents via heating conditions have been summarized in several studies [52][53][54][55][56][57][58]. To advance

• effective, the use of heating conditions resulted in a higher yield of the corresponding products. This advancement prompted scientists to explore alternative pathways for generating amidyl radicals, as an alternative to the traditional SET reduction of the N–O bond [80][81][82]. The SET reduction is able

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

• (Scheme 24). Further heating on the Au(111) surface led to products with partial skeletal rearrangement, driven by intramolecular structural strain. Both nanographenes, 186 and 187, contain six formal azulene subunits and exhibit nearly planar geometry. However, theoretical analysis of NICS values

• -dibromoazulene (203) was annealed on an Au(111) surface, leading to the formation of 2,6-polyazulene chains 204. Upon heating these chains to 730 K, laterally fused chains were observed. The distinctive phagraphene nanoribbon 205 and the THP-graphene nanoribbon 206 were formed. This transformation provides solid

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

• heating process. T90 and CY of [3.3.3]_branch (415 °C and 64 wt %) were lower than those of [3.3.3]_linear because of two-step decay profile (Figure S703a in Supporting Information File 1). All the samples showed broad powder X-ray diffraction (PXRD) patterns with unclear peaks at around 2θ = 11° and 20

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

• )-configurations, respectively. The macrocyclization study of borrelidin was subsequently carried out using model compounds 155a and 155b (Scheme 24). Heating compound 155a in dichloromethane for 18 hours in the presence of 5 mol % Grubbs’ second generation catalyst yielded coupling product 156a and unreacted

• starting material 155a. Encouragingly, the addition of an extra 5 mol % of the catalyst followed by further heating for 28 hours successfully converted the remaining 155a into 156a, which was isolated in 54% yield. A trace amount of an unwanted dimer of 155a was also detected. In contrast, different

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

• processes with high energetic costs such as heating or applying high pressure. Seeking to find an eco-friendlier method to strip the gold from carbon, the Stoddart group investigated the use of α-CD in a series of tests at the laboratory scale in which suspensions of KAu(CN)2-loaded carbon (50 mg

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

• into the near-IR (λem = 780 nm, ϕ = 0.8% in toluene). While the ϕ of TTM-TTM is low, no photoluminescence has been reported for PTM-PTM. ΔEST of TTM-TTM is at −1.22 kcal mol−1 indicating a singlet ground state as well; however, the value is larger than for PTM-PTM, requiring heating to observe

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

• achieved by a few-step transformation starting from brevicolline ((S)-1) isolated from natural sources (Scheme 2) [19]. When heating (S)-1 in benzoyl chloride, opening of the pyrrolidine ring and N-benzoylation occurred, resulting in compound 9. Debenzoylation of the latter to 10, followed by the catalytic

• 21 under extremely harsh conditions (100 °C, 130 bar), followed by N-acetylation gave a mixture of diastereomeric racemates 22, which was cyclized to a diastereomeric mixture of β-carboline derivatives 23. Heating of 23 in pivalic acid in the presence of a catalytic amount of trifluoroacetic acid

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

• (Scheme 3A). The mesylate could be cleanly substituted with azide by heating substrate with excess NaN3 in DMSO (Scheme 3B). With an excess of Schwartz’s reagent, the carbonyl was cleanly reduced to give 1,3-oxazine 62. Contrary to what we had initially predicted from literature precedent, there was no

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• formation of O-QC2 was achieved after 15 minutes (Supporting Information File 1). Next, thermally induced back-conversion to Q-NBD2 was attempted by heating the sample to 50 °C overnight. This process resulted in the initial formation of O-UnS2, followed by further rearrangement, consistent with the

• isomerizes into another species with prolonged irradiation. The formation of the same species was also observed while attempting the back-isomerization of O-QC2 to O-NBD2 at elevated temperatures. However, prolonged heating resulted in rearrangement to a 4th unidentified species. Clean recovery of O-NBD2

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• Schlenk vessels at a Schlenk unit/oil pump vacuum under nitrogen atmosphere. The stated reaction temperatures are the respective values of the silicone oil heating bath. All reactions were stirred with an electric magnetic stirrer. 1H, 13C, and 19F NMR spectra were measured at room temperature with a JEOL

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• advantages over conventional heating, such as enhanced reaction rates and yields [17]. Microwave irradiation is also aligned with our group’s sustainability goals of adhering to the principles of green chemistry [18]. Following our previous works in the synthesis and evaluation of biologically active

• were first verified using different equivalents of KOCN at different temperatures in water under microwave heating conditions (Scheme 1, Table 1), and 5.0 equiv of KOCN and microwave irradiation at 80 °C produced the best yield for H1a (Table 1, entry 2). Inspired by the simplicity of the procedure, a

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

• colorless crystals from the reaction between Et3N and CH2Cl2 at 100 °C in DMF. Subsequently, the corresponding α-aminophosphonate 35a was obtained by heating 36a with an equal amount of diethyl phosphite (Scheme 28b). Furthermore, when the reaction was carried out with CD2Cl2, the corresponding deuterated

• formaldehyde and ammonia in situ by heating [83]. Under these conditions, the water present in hydrated HMTA is sufficient for this hydrothermal decomposition to occur. On the other hand, an excess of ammonia must be added to the reaction mixture to shift the equilibrium towards the imine. Using this procedure

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

• reactions) Dry Mg turnings (excess) were added to an oven-dried 100 mL Schlenk flask and mechanically activated via stirring and heating. After 1 h, dry THF (20 mL) and 9,10-ANTH(Br)2 (84 mg, 0.25 mmol) were added. Several activation methods were tried (ultra sonic bath, careful heating, addition of I2

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• was observed, and the alcohol intermediate was isolated in pure form. In both cases, quantitative bromination was achieved by heating the compounds in concentrated aqueous hydrobromic acid, which after evaporation afforded the pure compounds 4b–d. To generate iodide 4e, alcohol 11 was isolated and

• 3b in almost quantitative yield. The bis(3-bromopropyl)-modified ligand 3c was generated by heating preQ1 together with bis(3-hydroxypropyl)amine. It is noteworthy that the amine exchange reaction is thought to proceed via a purine methide intermediate [11]. Subsequent treatment of the diol with

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• resulted in 40% yield. Alternating grinding and irradiation, the authors managed to obtain quantitative conversion of 2.1 to 2.3. Overall, in this work, mechanochemistry worked akin to agitation provided by stirring or heating in solution. In fact, 1H NMR spectroscopy, XRD and DFT analyses showed that

• Na2CO3 was ground in a mortar at room temperature for 3–5 min. Second, the reaction mixture was transferred into a quartz tube, heated to 50 °C (heating mantle) for 18 h, while being irradiated with blue LEDs under air-equilibrated conditions. In these conditions, product 3.3 was isolated in excellent

• starting materials. The authors also noted that the reaction proceeds in the dark upon vigorous heating (120 °C). The reaction could be performed on a gram scale as well, leading to the formation of 3.3 in 92% yield. The examples described above demonstrate that manual grinding offers simplicity and low

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• the formation of trichlorosubstituted 1,3-tropolones 7a,b as the main reaction products (Scheme 2). Heating 2a,b in acetic acid with a two-fold excess of o-chloranil (3) (method B) is accompanied by the formation of tetrachlorosubstituted 1,3-tropolones 8a,b (Scheme 2 and Supporting Information File 1

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• Dried acetonitrile (10 mL) was used to prepare a solution of compound 5 (251 mg, 1.0 mmol) followed by addition of anhydrous K2CO3 (173 mg, 1.25 mmol) under continuous stirring and heating. After 30 minutes, the solution of the respective 2-chloro-N-aryl/benzyl/cyclohexylacetamide 6a–h (1 mmol) in dry

• -benzothiazine-N-aryl/benzyl/cyclohexylacetamides 7i–n Dried acetonitrile (10 mL) was used to prepare a solution of compound 5 (1.0 mmol, 251 mg) followed by the addition of anhydrous K2CO3 (297 mg, 2.15 mmol) under continuous stirring and heating. After 30 minutes, the solution of respective 2-chloro-N-aryl

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• [4][5][6] and polymerization processes of unstable methylidene adducts [7][8][9], instead of the desired formation of a monocrotonic product. Therefore, heating [6][10][11][12][13][14] or Lewis acid activation [15][16][17][18] have often been used in the literature for successful multicomponent

• formaldehyde (generated from paraformaldehyde upon heating), an adduct of a methylidene derivative of a CH acid dienophile was detected in some cases only in reference [15] (when carrying out the reaction in a sealed tube in the presence of copper(II) acetate). However, in most reactions only the hetero-Diels

• ) are worth mentioning since according to the literature, unstable crotonic condensation adducts are usually generated upon heating [6][10][11][12][13][15], in acidic medium [15][23] or using oxidizing agents [24][25]. Three-component reactions under diffusion mixing conditions Under optimized

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• fashion, substituted indolopyrimidone derivatives 7a–e were obtained within 3 h in 31–90% total yield (2 steps) upon heating with formamide (Scheme 5). Next, we characterized certain physicochemical properties of the newly synthesized compounds. The absorbance and emission spectra of 5–7 were obtained

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• demonstrated that polysarcosine-based self-assemblies could undergo shape transformation via dehydration induced by heating [16]. This dehydration of the polysarcosine caused in their system a complete shape transformation but it would effectively also reduce membrane permeability and enhance osmotic pressure

• , as temperature is a factor in the van ‘t Hoff formula for osmotic pressure [21]. Additionally, dehydration strengthens polysarcosine chains interactions [16], potentially rendering the membrane too rigid for shape transformation. This means that the heating of the vesicles made with polysarcosine

• the thermogram unveiled a peak during the initial heating cycle, spanning from 40 °C to 90 °C (Supporting Information File 1, Figure S18). This peak corresponds with the dehydration temperature of polysarcosine, suggesting its role in facilitating subsequent shape manipulation [16]. The assembly of

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• identify the highest yielding reaction times (reaction stopped at 10, 15, 30, 45, 60, 75, and 90 minutes) revealed that longer stirring when heating is applied is not beneficial. In general, soon after the optimal reaction times indicated in Table 1, the yield progressively decreases when the reaction

• structures both prior to and following the production of the target compounds. The application of mild heating is crucial to reach full conversion of the starting materials in the times indicated in Table 1. However, conversion to the desired products is also achievable at room temperature over 18 hour

• stirring with minor yield loss. Increasing the heating temperature up to 110 °C does not lead to increased product yields (for more information on the optimization process, see Supporting Information File 1, page S19). The use of diethylenetriamine (DETA) was also investigated to evaluate its impact on the

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• to increase the experimental throughput. Commonly, batch platforms include a liquid handling system for setting up reactions based on a plunger pump (e.g., syringe, pipette), a reactor capable of heating and mixing, and in-line/online analytical tools. HTE in batch excels in the control of

• , stirring, heating, and cooling modules for enhanced versatility. In addition, the platform is capable of performing under inert and low-pressure atmospheres, handling separation steps, and pressure sensing for reaction monitoring. Its efficacy and robustness were confirmed through the successful synthesis

• laboratory (ASL) was designed and built by Eli Lilly [33]. This state-of-the-art facility allowed for heating, cryogenic conditions, microwaving, high-pressure reactions, evaporation, and workup, empowering researchers to conduct an extensive array of chemical reactions. The ASL comprises of three bench

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• Supporting Information File 1 (Figure S36). Comparative bar graph summarizing the thermal behavior of Fn, BTP6, and PHn derivatives (2nd heating DSC data). Representative S/WAXS patterns of Fn and Gnm compounds. Absorption (a) and emission (b) spectra of F6 and G66, measured in different solvents at a