Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• petroleum ether/Et2O (see the Experimental section). Generally, the reactions are fast and afford products in high to excellent enantiomeric purities. The substitution pattern in the phenyl ring has some influence on the results (compare compounds 3a–d). The ortho-Cl substituent in the aromatic ring of 1b

• monitored by 1H NMR analysis. After completion of the reaction, the product was isolated by direct precipitation from the crude reaction mixture by adding a mixture of petroleum ether/Et2O (4:1; 2 mL). The product was collected by filtration and washed with a mixture of petroleum ether/Et2O (4:1; 4 × 2 mL

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• strong affinity of zirconium for oxygen atoms [4][21]. Building on this concept, they envisioned that a similar reaction system could be applied to the homolytic cleavage of C–O bonds in alcohols and ethers. When benzyl alcohol and ether derivatives 49 were treated with zirconocene in the presence of a

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• vary widely across the literature, with solvents ranging from neat conditions to cyclohexane, hexanes, toluene, benzene, carbon tetrachloride, dichloromethane, and diethyl ether. Reaction temperatures span from −10 °C to 100 °C. The first detailed investigation of this transformation was reported by

• ]. The reaction appears limited to electron-rich chromanones, as evidenced by decreased yields upon removal of the electron-donating ether substituent (e.g., compound 90). The authors further noted that the products require cold storage due to their sensitivity. Deoxychlorination with acyl chlorides: The

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• more stable methyl carbonate 8b, readily obtained from maltol (2) via treatment with methyl chloroformate in the presence of base, we found that methylation under typical conditions (LiHMDS, MeI) yielded only a complex product mixture (Table 2, entry 2). Methyl ether 8c was identified as a suitable

• . Subjecting maltol (2) to trimethylsilyl chloride and triethylamine furnished the corresponding silyl ether 8d in nearly quantitative yield (Table 2, entry 4). Due to the instability of the trimethylsilyl ether functionality to flash column chromatography, methylation of 8d was followed by desilylation with

• ) group. Protection of maltol (2) with tert-butyl(dimethyl)silyl chloride (TBSCl) afforded silyl ether 8e in 99% (Table 2, entry 5). Indeed, methylation of the lithium dienolate of 8e with methyl iodide at 0 °C afforded TBS-protected ethylmaltol (9e) in 64% with no trace of maltol (2). Subsequent

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• solvent was removed in vacuo. Product 2f (1.02 g, 4.8 mmol, 68%) was isolated by column chromatography on silica gel (Rf = 0.15, petroleum ether/ethyl acetate, 40:1). Procedure for deprotection of 2f (experimental details for Scheme 3, reaction 2): Acetyl chloride (4.5 mL, 63.3 mmol) was added dropwise to

• . Product 3f (0.79 g, 3.76 mmol, 94%) was isolated by column chromatography on silica gel (Rf = 0.40, petroleum ether/ethyl acetate, 3:1). Procedure for nitration of 3f (experimental details for Scheme 3, reaction 2): 2-Nitro-2-(nitro-NNO-azoxy)-1,3-propanediol 3f (0.63 g, 3.0 mmol) was added in portions to

• with water (30 mL), brine (30 mL), dried over Na2SO4 and solvent removed in vacuo. Product 4f (0.71 g, 2.37 mmol, 79%) was isolated by column chromatography on silica gel (Rf = 0.55, petroleum ether/ethyl acetate, 5:1). Reaction in divided electrochemical cell (experimental details for Scheme 4

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• acetic acid. The reaction was carried out at room temperature and with vigorous stirring for 15 minutes. Next, the solvent was removed and the residue was purified using column chromatography (eluting with diethyl ether/hexane 1:8, then acetone/hexane 2:1 to give products 2 and 3. Procedure for oxidation

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• , hydroboration/oxidation, and an oxidative cyclization protocol. The diastereomers were separable by column chromatography, leading to this faster and more scalable procedure to be performed preferentially over a six-step diastereoselective sequence. After silyl ether deprotection, the Wagner–Meerwein-type

• afford cyclization of the E-ring. The obtained pyridinium species was directly reduced to reveal the piperidine moiety. The observed selectivity for hydrogenation from the α-side was attributed to the steric hindrance of the C20 axial tertiary TMS ether. The survival of the olefin in the D-ring was

• attributed to the hindrance by the axial benzyl ether group on one side, and the C7 axial TBS ether group on the other. Removal of the silyl groups at C7 and C20 with CsF was followed by dihydroxylation of the C14,15-double bond, and the major product 105 was determined to be the desired α-diol by 1H–1H

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• intermediates 40‒43 to chloro derivative 44, which was converted with amines to compounds 45 and with methanol to ether 46. Finally, we synthesized related tetracyclic derivatives containing the ethylenedioxy moiety attached to positions 2 and 3 of the dibenzo[c,f][1,2]thiazepine (1) core (Scheme 8). While the

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

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

• , obtained as a 1.7:1 mixture of diastereomers after protection of one of the carbonyl groups in 19 as enol ether with BOMCl. A silyl-tethered intramolecular Diels–Alder reaction of the in situ generated 22 constructed the tricyclo[5.2.1.01,5]decane core bearing a cis-pentalene unit, yielding compound 23

• deprotection of the cyclization precursor was essential, as the TES-protected analogue of 35 failed to deliver the desired spirocycle 38 under the Nazarov cyclization conditions. α-Oxidation of 38 with molecular oxygen afforded 39, which was then converted to 40 via formation of a chloromethyl silyl ether

• ). Chemoselective epoxidation of the enone double bond in 69 yielded epoxide 70. A Wittig reaction of 70 with (methoxymethyl)triphenylphosphonium chloride and t-BuOK generated a methyl enol ether, which was unstable in the presence of the epoxide. During aqueous workup, simultaneous hydrolysis of the enol ether and

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• the tropical rain forests of the Kalimantan region (Indonesia) [1][2]. These cyclic ether natural products belong to the typical aryltetralin lignans, which have already attracted broad attention from the synthetic community [3][4][5]. Zhu and co-workers disclosed a concise synthesis of (±)-aglacins B

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• precipitate was recovered by filtration and washed several times with ethyl ether, to give pure compound 3 (118 mg, 96% yield). Characterization of compound 3: NMR spectra were acquired on a Bruker Avance 400TM spectrometer. Chemical shifts (δ, ppm) are reported referring to the residual peak of the solvent

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• ring contraction of (S,S)-carveol-derived TBS ether 163b with triethylborane (Scheme 31). This reaction proceeded with isomerization and formation of the intermediate carbocation 181, which underwent 1,2-carbon migration to form the cyclopentane product 182. A sequence of oxidations of borane 182 with

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• consideration are all effective in facilitating the dissolution of nitrone. However, under identical conditions, the nitrone was not fully soluble in solvents such as water, diethyl ether, petroleum ether, triethylene glycol, diethanolamine, and glycerol. Then, these solvents were selected with the known

• ]. In the case of castor oil, although all of the starting material was converted into the respective cycloadduct, the yield of the product was found to be lower than that observed in other solvents (Table 1, entry 6). This was primarily attributable to the utilization of a hexane/diethyl ether mixture

• corresponding products were readily isolated as a mixture of diastereoisomers by precipitation from the reaction medium with the addition of solvents such as hexane, octane or a diethyl ether/hexane mixture. As Welton asserts, the environmental friendliness of a chemical process is contingent upon the

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• isolated via a formal [4 + 1] annulation pathway [46] (Scheme 4). Since the hydroxy group interrupted the C–H insertion, it was protected as the TES ether 23 and subjected to the same conditions. However, the reaction only afforded the C–Si insertion product 24 [47]. Based on the above results, although

• the β-lactone was converted into the linear methyl ester 19 to decrease the potential steric hinderance associated with the fused bicyclic skeleton, substrates containing a free hydroxy group or the corresponding TES ether still failed to close the cyclopentene ring. In this scenario, it was necessary

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• selective recognition. Balancing binding affinity and selectivity through precise conformational engineering remains a critical challenge [11]. Previous studies, such as those by Tian et al. [12], demonstrated selective binding in chiral assemblies via crown ether chain-length modulation. The dynamic

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• reported in 2014 the first examples of rotaxanes with a dithienylethene switch on the axle [57]. They synthesized [3]- and [5]rotaxanes with a symmetric axle containing a dithienylethene in the center and alkylammonium binding sites on each side, which interact with N-hetero crown ether macrocycles

• acridane photoswitch directly into a crown ether macrocycle [82]. However, the synthesis proceeded with very low yield, and the small amount of rotaxane obtained was immediately converted to the acridinium form during purification. Attempts to regenerate the acridane were unsuccessful. Nevertheless, the

• composed of a large crown ether macrocycle containing two anthracene moieties and an axle consisting of dibenzylammonium hexafluorophosphate [83]. Light-induced anthracene dimerization reduces the macrocycle’s cavity, strengthening its interaction with the axle. As a result, the initially rapid dethreading

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• desired methyl group at its α-position to afford 51 in racemic form. This seemingly straightforward α-methylation turned out to be quite challenging. Tsukano and co-workers eventually utilized a two-step sequence to solve this problem, namely, TMS enol ether formation followed by trapping the enol ether

• TMSN3 recently developed by Xu and co-workers [34]. Mukaiyama conjugate addition between 60 and 61 promoted by Tf2NH followed by a one-pot enol ether hydrolysis gave 62 as a mixture of inconsequential stereoisomers. Subsequent oxidative cleavage of the terminal olefin of 62 using ozonolysis followed by

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• -chloroperoxybenzoic acid) induced epoxidation, which was then followed by a Meinwald rearrangement to accomplish aldehyde 7. From 7, a sequence involving silyl enol ether formation, Simmons−Smith cyclopropanation, and acid-mediated regioselective ring-opening installed the C8 quaternary methyl group in 10. Subsequent

• alkylation with aldehyde 102, producing 103, which was then protected as its OMOM ether to yield 104. One-pot hydrogenation of quinone 104 afforded the corresponding hydroquinone, which, upon subsequent methylation, furnished 105. Removal of the MOM group from 105 followed by oxidation of the resulting

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• discern the effect of smaller aromatic sidewalls. The synthesis of acyclic CB[n]-type receptors follows a building block approach involving the reaction of a glycoluril bis(cyclic) ether with an activated aromatic wall by a double electrophilic aromatic substitution process [30]. Scheme 2 shows the

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

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

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

• converted into the silyl enol ether 12 and treated with Selectfluor, fluorinated ketone 13 was formed as the major product after aqueous workup (Scheme 2). When the solution of 13 was concentrated following flash column chromatography, rapid decomposition was observed, which may explain failures with many

• demonstrated that halogenation reactions with 15 were viable, but dependent on the characteristics of the electrophile. To avoid the elimination of the amine, β-methyl ether 16 was prepared. The reaction of ketone 16 with Selectfluor promoted by ʟ-proline in MeOH/MeCN, which ensured that the equilibrium

Enantioselective radical chemistry: a bright future ahead

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

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

• functionalization of the terminal carbon atom of the silyl polyenolate. In the reaction of silyl tetraenol ether 47, selective reaction at the η position occurred, and the product 48 was obtained in 78% yield and 96% ee. Conclusion This perspective highlights important contributions in the area of enantioselective

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• 1,5-enynes 1 as substrates involving alkyne alkoxylation and dienol ether aromaticity-driven processes (Scheme 2) [8]. The reaction pathway was decisively influenced by the choice of solvent. Under gold catalysis, with toluene as the solvent and 2 equiv of methanol serving as the nucleophile, the

• reaction proceeded via 5-endo-dig cyclization. This pathway involved enol ether attack on the gold-activated alkyne, leading to the formation of oxonium intermediate 2. Subsequently, nucleophilic addition of methanol culminated in the formation of indene motif 5 (Scheme 2, path a). When methanol served

• nitrogen atom was substituted with strong electron-withdrawing groups, a nucleophilic attack to gold(I)-activated alkyne generated intermediate 38, with subsequent 6-endo-trig cyclization affording benzo[a]carbazole 39 (Scheme 9, path a). Conversely, the activated alkyne was attacked by enol ether to yield

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• conversion of a glycolaldehyde acetal (hydroxy acetal). The first step was the reaction of sodium benzyloxide with bromo acetals giving the hydroxy acetals in 75–82% yield. The intermediate ether was converted to the hydroxy acetal with sodium in liquid ammonia in good yield (70%). The hydroxy acetal then

• oxygen in alcoholic medium has also been reported (Scheme 37) [121][122]. Riguet synthesized γ-lactams through a Ugi 4-center 3-component reaction (U-4C-3CR) protocol. HFO was used as the electrophile in the Friedel–Crafts (FC) alkylation reactions of indole catalyzed by diphenylprolinol silyl ether. The

• HFO with benzoic acid amide or furan-2-carboxamide in 1:1 molar ratio at 70 °C for 4–8 h (Scheme 42, path c) [132]. The reaction of HFO with 2-methylfuran in a 1:2.2 molar ratio in diethyl ether solution at room temperature in the presence of catalytic amounts of perchloric acid for 5 hours led to the

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• donor, securing the desired secondary alcohol product in excellent enantioselectivity (99% ee). Protection of the alcohol group with TBDPSCl gave silyl ether 64 in high yield (79% for 2 steps). Subsequently, successive four manipulations including dehydrogenation, Morita–Baylis–Hillman reaction

• 69 and lactone 70 at 456 nm with fac-Ir(ppy)3 as the photocatalyst furnished a mixture of isomeric olefins. Finally, DBU-promoted the isomeric olefins conjugation and removal of the two silyl ether completed the first total synthesis of (+)-randainin D (13). Total synthesis of (−)-hunterine A and

• Scheme 8 [72], the easily prepared substrate underwent the CBS reduction conditions and protection of the resulting secondary alcohol with TBSCl to afforded silyl ether ketone 90 in 46% yield (two steps, dr = 40:1, 92% ee) [8]. Horner–Wadsworth–Emmons (HWE) reaction of 90 followed by Cu-carbene migratory

Bioinspired total syntheses of natural products: a personal adventure

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

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

• benzylic oxidation to generate a para-quinone methide (pQM) intermediate. Using fusarentin 6-methyl ether as an example, pQM intermediate 10 would be generated. The C10 alcohol should successively undergo an oxa-Michael addition reaction to close the THF ring, providing 7-O-demethylmonocerin. Similarly

• , Wittig reaction with MOMPPh3Cl and LDA gave the putative methyl enol ether, which could be directly converted into 1,3-dithiane 12 with propane-1,3-dithiol. Nucleophilic addition to chiral epoxide 13 and oxidative hydrolysis of 1,3-dithiane to ketone delivered chiral β-hydroxyketone 14. Evans−Tishchenko

• unreacted, which released the secondary alcohol, followed by BCl3-promoted selective cleavage of the isopropyl and one methyl protection ultimately furnished thenatural product fusarentin 6-methyl ether. With fusarentin 6-methyl ether in hand, we explored the bioinspired oxidation/oxa-Michael addition. This