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

• -metathesis reaction smoothly in the presence of the Hoveyda–Grubbs second-generation catalyst to afford the enone 13 in 63% yield with the desired trans-configuration. Enone 13 was then subjected to the Pd/C-catalyzed hydrogenation to give the thermodynamically favored bicyclic hemiketal 21 in 92% yield as

• intermediate 22 (see Supporting Information File 1 for the details). Reasoning that the preferential coordination of the palladium catalyst with the hydroxy group at C15 and the carbonyl group at C18 in compound 22 may have deactivated the palladium catalyst [34], we protected the hydroxy group. Compound 22

• controlled by the stereoelectronic effect of the axial hydroxy group at C11 (Scheme 4) [28]. First, β-keto ester 21 was synthesized (Scheme 5). Cross-metathesis of allylic alcohol 18 and olefin 28 with the assistance of the Hoveyda–Grubbs second-generation catalyst delivered the desired product 27 in 68

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• . PPL-catalyzed desymmetrization of 10 with vinyl acetate yielded monoacetate (R)-11 in 41% yield (94% brsm) with 78% ee. Diene 12 was prepared from (R)-11 via a ten-step sequence. The following ring-closing metathesis (RCM) reaction catalyzed by Grubbs catalyst 13 converted 12 into the bicyclic

• . Alcohol 28 was obtained from 27 in two steps, and was subsequently converted to hyperione A (30) and ent-hyperione B (31) by refluxing in toluene with Shvo’s catalyst 29. Notably, the authors found that hyperione A (30) could be obtained in higher yield and enantiopurity from alcohol 28 via a two-step

• enantioselective acylation of glycerol derivatives [53]. Since then, desymmetrization strategies for prochiral 1,3-diols involving transition-metal-catalyzed acylation have been developed. Trost and co-workers then developed a Zn-based catalyst for asymmetric aldol reactions [54][55], later adapting it to the

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the

• multiplicity of reaction types between rhodium carbenoids and the many different co-substrate classes, and the catalyst-driven selectivity between these pathways. The probes were screened for activity against Trypanosma brucei, and four probes with promising anti-trypanosomal activity were identified

• a co-substrate (5 equiv; 16 μL of a 6.25 M solution in CH2Cl2) were added to glass vials in a 96-well reaction block, and the solvent left to evaporate after each addition. Subsequently, a dirhodium catalyst (1 mol %; 200 μL of a 1 mM solution in CH2Cl2) was also added to each vial. The final volume

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

• framework of the diol precursors, predominantly axially chiral structures such as BINOL, H8-BINOL, SPINOL and VAPOL scaffolds, which are widely used in the development of CPA catalysts. Furthermore, the ortho-aryl substitutions of the CPA catalyst can efficiently modulate the stereochemical and electronic

• ortho-positions. The dual hydrogen-bonding interactions were critical for this reaction, ensuring that the reaction proceeded within the chiral pocket of the CPA catalyst. Moreover, the authors proposed that the extended π-substituents at the ortho-positions of CPA could engage in π–π-stacking

• interactions with the enehydrazine intermediate, which is essential for achieving high levels of stereocontrol. Using the optimal catalyst CPA 1, a series of aza[6]helicenes 3a,b was synthesized with excellent enantioselectivity and high yield. However, this method demonstrated notably reduced efficiency and

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• Pricilla Matseketsa Margret Kumbirayi Ruwimbo Pagare Tendai Gadzikwa Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States 10.3762/bjoc.21.144 Abstract We systematically lipophilized an amine-based metal-organic framework (MOF) catalyst and applied the

• groups. This selective functionalization yielded MOFs in which the catalytically active amines are confined within highly lipophilic pores, reminiscent of many enzyme active sites. We determined that systematically increasing the lipophilicity of the pores results in a commensurate increase of catalyst

• catalytic performance and/or systematically investigate the influence of a particular chemical or structural property on catalyst efficiency [23]. For examples of tailoring the pore environment in MOF-based catalysts to modulate catalytic performance, we can refer to the elegant work of Telfer and co

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• molybdenum catalyst allows partial conversion of the recovered by-product to the final product 35b, while for the S-heterodiazocine lead was used for the reduction in neat conditions (Scheme 14) [53]. N-Heterodiazocines (Scheme 15) can be synthesised by coupling of monoprotected diamine 55 with benzyl

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

• [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

• , the present C–H annulation reaction of aniline (1a) with styrene (2a) was initially carried out in TFE (trifluoroethanol) as solvent in the presence of 25 mol % FeCl3·6H2O as a catalyst and 1.5 equiv of TFA (trifluoroacetic acid) as an additive (Table 1, entry 1). For this reaction, 12% of 2,4

• , FeCl3·6H2O provided the best results (Table 1, entry 2). A further reduction in catalyst loading from 25 mol % to 20 mol % and 10 mol % resulted in a noticeable decrease in both selectivity and conversion efficiency (Table 1, entries 7 and 8). This is likely due to insufficient C(sp2)–C(sp2) bond

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• successful as the reaction was stopped at the spirocycle 4d formation stage (Table 1, entry 9). The removal of the N-Alloc group in unsaturated ester S-3d was performed using a Pd catalyst and pyrrolidine as a nucleophile. The use of Pd(PPh3)4 as the catalyst led to a fast consumption of the starting

• analogously from ester R-3d. Thus, Alloc was validated as non-expensive and relatively small N-protecting group, removal of which is compatible with double bond and acetal function of amides S-5 and R-5. The removal of the Pd catalyst at laboratory scale was done by chromatography. For large scale synthesis

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• coordination of the boron center with the remaining C2-OH group increases its acidity, thereby generating in situ an acidic catalyst for the activation of the glycosyl donor [62][63]. In this approach, the use of glycosyl phosphites of gluco- (35) and galacto- (38) configuration as donors, in combination with

• lactol 42 afforded the corresponding 1,1'-linked diglucosamine 43 in almost quantitative yield in the borinic acid-promoted glycosylation with the phosphite donor 35 (Scheme 4). This outcome was attributed to the involvement of the NH group in complex formation with the borinic acid catalyst, suggesting

• addition, 2-amino-2-deoxy-1,3-diols were successfully employed as glycosyl acceptors, as exemplified by the use of GlcN-derived lactol 42, which was reacted with the 2N-Troc-protected GalN phosphite donor 47 in the presence of borinic acid catalyst to give the β,α-1,1'-linked disaccharide 48 (Scheme 4) [63

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

• technologies including ultrasonication, microwave irradiation, and microreaction technology into conventional nitration frameworks. Nikseresht et al. developed a novel heterogeneous heteropoly acid catalyst (PMA@MIL-53(Fe)), enabled efficient regioselective nitration of phenols under ultrasonic irradiation

• (11%), dichloroethane (8%). and acetic acid (8%) (Figure 4b), which are particularly valued for their ability to dissolve both organic substrates while maintaining chemical stability under the reaction conditions. Notably, sulfuric acid plays a dual role – as catalyst and solvent – in these systems, a

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• halogen atom transfer (XAT) agent [17][18]. Standard reduction potentials illustrate that hypophosphite is a powerful four-electron reductant [19]. Our previous studies have proved that NaH2PO2 can be a selective reducing agent in the catalyst-free reductive amination process [20][21][22] that can impart

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• ] involving 6-aryl-2-aminopyridines 27, aldehydes, and isocyanides (Scheme 5a) [35]. By employing chiral phosphoric acid (CPA) C1 as the catalyst, this reaction worked well to afford axially chiral imidazo[1,2-a]pyridines 28 in high-to-excellent yields (up to 99%) and enantioselectivities (up to >99% ee). It

• of the resulting products in developing chiral organocatalysts was investigated as well. For instance, 28a was converted to a thiourea-tertiary amine 29 through a four-step procedure in an overall 36% yield. This compound was then utilized as the catalyst in the electrophilic amination reaction

• condensation between 27 and the aldehyde afforded INT-A, which was activated by the CPA catalyst through hydrogen bonding interaction. The nucleophilic addition of isocyanide to Int-A produced INT-B bearing a stereogenic center. Subsequently, INT-B underwent intramolecular cyclization to generate axially

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

• group in compound 10. Compound 10 can be realized by introducing an ester group in 9, which is the [3 + 2 + 1] cycloadduct from 8 and CO using a Rh catalyst. The [3 + 2 + 1] substrate of yne-vinylcyclopropane (yne-VCP) 8 can be synthesized by Wittig reaction from cyclopropyl aldehyde 7, in which the

• . Applying the traditional solvent dioxane for the [Rh(CO)2Cl]2 catalyzed [3 + 2 + 1] reaction (the catalyst loading was increased from 5 mol % to 10 mol %) gave 9 in only 26% yield. To our delight, the reaction yield could be improved to 87% by using mesitylene [30] as the solvent and the loading of [Rh(CO

• )2Cl]2 catalyst can be reduced to 3.6 mol % (the reaction scale was 20.6 mmol). After finishing the key [3 + 2 + 1] reaction, we focused on building the D ring in 1. Initially, we tried to directly close the ring through addition of the α position of the carbonyl group to the bridgehead vinyl group

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• as the relative Lewis acidity of the catalyst (measured by the Child’s method [41][42][43]), but do not follow the same trend as the energy of the LUMO(dienophile). This finding therefore challenges the traditionally used LUMO-lowering concept as the ultimate factor controlling the catalysis in these

• LAs [66] (Table 2). As expected, we found that the reduction of the activation barrier (up to ca. 25 kcal/mol) directly correlates with the relative Lewis acidity of the catalyst. In addition, the process becomes more and more asynchronous as the acidity of the catalyst increases, which strongly

• significant reduction of the Pauli repulsion between the reactants in the catalyzed reaction. Therefore, once again we found that the LA catalyst induces a significant polarization in the reactive carbonyl group which (i) renders the process more asynchronous and therefore, less aromatic, but (ii) diminishes

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

• reaction. The highest yield of 3a (85%) was achieved by treating 1 with 3.2 equiv of the azirine in MeOH at 100 °С with 50 mol % of Ni(hfacac)2 (Table 1, entry 13). Lowering the temperature and the catalyst loading resulted in a slight deterioration in the yield and a significant slowing of the reaction

• -methylindole 9a with 2a, carried out in the presence of Ni(hfacac)2 (50 mol %), unfortunately, did not give any identifiable products. Experiments with the catalysts presented in Table 1 were also unsuccessful. Nevertheless, favorable outcomes were achieved through a substantial decrease in catalyst loading

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• in mannosyl PVB 8 (1.0 equiv) in the presence of TMSOTf as catalyst proceeded smoothly at 0 °C to room temperature, affording the α-Man-(1→3)-Man PVB disaccharide. The further coupling of the above PVB disaccharide with the poorly reactive 2-OH in mannoside 9 (0.9 equiv) under activation with NIS and

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

• formation; thus, keeping water content below 1% is necessary to maintain high reaction efficiency. The negative effect could be due to the decreased solubility of 2a at higher water content [42][43][44]. Hereafter, the readily available CuI was selected as a catalyst precursor to facilitate click reactions

• of volatile compounds from the aqueous phase by vacuum distillation, 88% of CyreneTM (13.7 g) was recovered. The reaction was repeated four times with the same procedure under identical conditions (same catalyst and substrate concentration). It was shown that CyreneTM could be successfully recovered

• , EtLev: ethyl levulinate, GVL: γ-valerolactone. Effect of the Cu source used in the click reaction of benzyl azide (1a, 1.15 mmol) and phenylacetylene (2a, 1 mmol). Reaction conditions: 2.5 mL CyreneTM, 1 mol % catalyst precursor, 0.1 mmol Et3N, T = 30 °C, t = 0.5 h. Copper-catalyzed azide–alkyne

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

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

• 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

• adduct 10 was identified using GC–MS (Figure S1, Supporting Information File 1). When the reaction was performed under air-equilibrated conditions, the intended product 9a was obtained in a 31% yield, indicating that air influenced the interaction between the Ni-catalyst and the α,β-unsaturated carbonyl

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

• the alcohols’ nature and catalyst amount (1–10 wt %). The CS600 catalyst demonstrated efficiency in the transesterification of low-molecular-weight esters, medium-chain triglycerides (C9–C12), and lactones, resulting in the corresponding methyl esters in 66–99% yields in the presence of low catalyst

• their manufacturing. The transesterification approach is an efficient way, which requires the use of a catalyst [44][45][46][47][48] and of course, there are many catalysts providing the desired transesterification products. However, the availability of the catalysts is limited, and the scope of

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

• experiment without a catalyst and observed only traces of the benzamide 2aa (Table 1, entry 1). However, we detected almost half of the salt 1a remained in the reaction medium after 10 hours of reaction (Supporting Information File 1, Figure S3). Thus, we settled with the similar conditions to the published

• . Unfortunately, 4CzTPN, 4CzIPN, and 3DPAFIPN did not demonstrate increased efficiency, and the yields of the target product 2aa were slightly lower than for [Ru(bpy)3](PF6)2 (Table 1, entries 4–6). Thus, all further optimization studies were done using [Ru(bpy)3](PF6)2 as a catalyst. After, we moved to the

• reactivity pattern in the current transformation, a reaction mechanism was proposed taking into the account the known data and control experiments (Scheme 4). Upon irradiation with blue light, the Ru(II) catalyst undergoes photoexcitation, followed by an oxidative single-electron transfer (SET) process with

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

• one of the most dynamic and versatile areas of contemporary chemical research. Once viewed primarily as a cost-effective alternative to noble metals, copper has emerged as a powerful and versatile catalyst, capable of mediating a wide array of chemical transformations through both two-electron and

• harness their Lewis-acidic and weakly oxidizing properties, respectively. In addition, microwave irradiation increases the reaction rate considerably. Furthermore, the use of a solid Cu(I) catalyst immobilized on an aminated silica support allows for a heterogeneous and cost-effective process, featuring

• straightforward workup and minimized free copper on solution. Due to this, the catalyst could be regenerated and reused in up to eight cycles. Upon optimization, this practical and versatile method could be used for the synthesis of several benzoxazole derivatives. A Letter was contributed by D’Andrea and Jademyr

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

• completed in 1.5–2 h. A solid Cu(I) catalyst supported on aminated silica made the process cost-effective and heterogeneous, thus simplifying work-up and minimising free copper in solution. The catalyst was found to be regeneratable and reusable for up to eight cycles. The optimised method facilitated the

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

• being applied when reacting amides to achieve their decarbonylation. In 2014, Cao et al. [47] reported the amination of benzoxazole with a secondary amine either in air or an O2 atmosphere, lowering the catalyst amount and the reaction temperature. In 2020, a study by De Vos and co-workers [48] focused

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

• using [Cu(MeCN)4]OTf instead of Rh2(Piv)4, the target product 3aa was obtained in higher yield (72%, Table 1, entry 2) and with [Cu(MeCN)4]PF6, the yield of 1,2-thiazole 3aa increased to 82%, while the reaction time decreased significantly (Table 1, entry 3). Using Cu(OAc)2 as a catalyst led to a slight

• 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

• expectations were not fulfilled. The exception is the data from entry 7 (Table 1), where the yield of compound 3aa was 78%. Thus, the conditions described in entry 7 (absence of a catalyst, use of 1.5 equiv of PhINTs 2a and dichloromethane (DCM) as a solvent at room temperature for 10 min) are optimal and were

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

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• reactions were carried out at ambient pressure (control) and under HHP (up to 3.8 kbar) conditions. These representative reactions provided higher yields for the products and HHP enabled truly green processes that are catalyst- and solvent-free, to occur with high yields and producing only non-toxic by

• -products. A computational study accompanies the experimental data to interpret the outcome of the reactions. Keywords: acetaminophen; acetylsalicylic acid; benzimidazoles; catalyst-free synthesis; cyclization; esters; high hydrostatic pressure; pyrazoles; Introduction Non-traditional activation methods

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

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

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