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

• compounds, and catalyst J as a trifluoroacetylated chiral tertiary amine, which lacks iodine. The reaction of imine 1 with dimethyl malonate was selected for the investigation as a model reaction. Based on our previous experience the catalyst screening was carried out in toluene in the presence of 10 mol

• , and malonate were carried out in the presence of 10 mol % of catalyst E in toluene at −20 °C (Figure 3). The experimental procedure was simple, enantiomerically enriched products 3a–i were isolated by direct precipitation from the crude reaction mixture in good to high yields by adding a mixture of

• method and applications of obtained products are under study. Experimental General procedure for the catalytic asymmetric Mannich reaction Catalyst E (2.7 mg, 0.0057 mmol, 0.01 equiv) was weighed into a reaction vessel, imine (0.057 mmol, 1.0 equiv) and toluene (285 µL) were added. The mixture was

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• reaction of S/R-1 with trimethtylsilylacetylene in toluene (Scheme 1). Subsequent deprotection of the trimethylsilyl (TMS) groups with tetrabutylammonium fluoride (TBAF) afforded the desired ligand S/R-3. The preparation of the target platinum(II) complex was performed by using a similar procedure of other

• (112 mg, 0.0962 mmol) and trimethylsilylacetylene (0.40 mL, 2.9 mmol) was added degassed solution of Et3N (2.6 mL, 19 mmol) and toluene (5.2 mL) by argon bubbling. The reaction mixture was refluxed at 90 °C for 21 hours. After cooling to room temperature, the reaction mixture was filtered through

• −1. The R-isomer was synthesized using a similar procedure to that of the S-isomer, except that compound R-1 (300 mg, 0.52 mmol), trimethylsilylacetylene (0.30 mL, 2.2 mmol), CuI (32 mg, 0.17 mmol), Pd(PPh3)4 (112 mg, 0.096 mmol), Et3N (2.3 mL) in toluene (4.5 mL) were used. The yield was 78

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

• compounds 15 and 18 without contamination with E- or Z-16 isomers (Scheme 4). Additionally, it was found that several aqueous work-up procedures induced ring opening of compounds 17 and 18. Ultimately, steam distillation directly from the reaction mixture afforded a toluene solution of compounds 15 and 18

• in a combined yield of 44% (Scheme 4). Additional optimization reactions showed that when the reaction was carried out at −10 °C even in the absence of Hünig’s base dichloride 15 could be obtained in 92% yield. Treatment of 15 with KOt-Bu in toluene gave the desired compound 19 in 43% yield. The

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• relatively simple protocol (Pd(PPh3)4, toluene, NaOH, 90 °C, 12 h) and the reported high yield of 4-prenylindole, we consistently obtained inseparable mixtures of the desired prenylindole and the reverse indole products. Mixtures of prenylated compounds have been observed under the same conditions with 4

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

• in refluxing toluene, giving 99 in 88% yield as a single diastereomer. Due to steric hindrance, dienophile 98 would approach the more accessible face of diene 97, i.e., cis to C8–H. Furthermore, exclusive endo-addition was observed because exo-addition would lead to severe interference between the

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ], diammonium phosphate (DAP) [43], and tetrabutylammonium bromide (TBAB) [44]. Organic bases like morpholine [45], triethylamine [46], ethanolamine, and piperidine [47] and heterogeneous catalysts from Cu [48], Ti [49], and Zn [50] metal compounds have also been used. Common solvents are ethanol [51], toluene

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• . First, SG, chosen as the solid substrate, was reacted with an excess of 3-aminopropyltriethoxysilane (APTES) in toluene under reflux to obtain a-SG material with amino groups introduced on the SG surface [15][16]. In the second step, a-SG was treated with BU1, in the presence of 1-hydroxybenzotriazole

• Silica gel (8.01 g) was dispersed in toluene (24 mL) and stirred under argon atmosphere, while heated up to 115 °C. Then, APTES (6 mL) was added, and the dispersion was stirred under inert atmosphere at elevated temperature for 5 h. After cooling, the dispersion was filtered, washed thoroughly with

• toluene, ethanol and acetone to remove unreacted APTES and dried in vacuo (50 °C) overnight in order to get a-SG [15][16]. Further, to prepare covalent SG-NHCO-BU1, a-SG (0.9 g) was suspended in DMF (15 mL) and shaken at ambient temperature for 30 min. BU1 (0.1 g, 1 equiv) was dissolved in a minimum

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• higher oxidation potential (E1/2 = +1.52 V). This reaction was examined using different solvents, and it was found that toluene and 1,4-dioxane gave low yields (4–5% yield). Under blue LED irradiation, Ir-based PC is photoexcited, and its excited state is reductively quenched by the electron-rich arene

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• formation of carboxylic acid 9bA, isolated in 71% yield (Scheme 7). In addition, an attempt to cyclize 6b in the presence of DBU without a solvent at 110 °C led to significant destruction of the substrate and product 9b was obtained with a yield of about 20%. Cyclization of substrate 4a with NaH in toluene

• ,b, and 8a were obtained in 62%, 55%, and 45% yields, respectively. In turn, the suitable reaction conditions for cyclization of substrates 6a–c were their treatment with excess Mg(OMe)2 in a solution of methanol/toluene, which afforded products 9a–c in 66–73% yield. It should be noted that the bases

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• substrate 9f was subjected to the optimized conditions, which resulted in both a lower conversion and yield (Table 1, entry 9). In contrast, when the reaction of 9f was performed in a mixed MeCN/toluene 10:1 solvent, the conversion of substrate 9f to product 10f decreased, but the yield increased to 56

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• five-membered ring due to the formation of an intramolecular hydrogen bond (Figure 2A). It has been shown that furanoside is preferentially formed in nonpolar solvents such as toluene. This form was successfully fixed and purified as benzoate derivative. Bulky substituents can also stabilize the

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

• Me2S to give dialdehyde 28 and reaction of compound 28 with colloidal potassium in toluene. During aldol condensation in the presence of morpholine-camphorsulfonic acid (CSA) or ʟ-proline, a stable aldehyde 30 was isolated in yields of 50% and 75%, respectively. Decarbonylation and corresponding

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

• for the preparation of such cyclic compounds and/or their fused cyclic systems typically necessitate the use of toxic solvents, including chloroform, benzene, toluene etc. [32][53][54][55][56][57][58][59]. Indeed, the selection of conventional organic solvents, including benzene, toluene and

• ADMETLab 3.0 platform [87] are illustrated in Figure 2a. Conversely, the oral toxicity values of methyl laurate, in conjunction with toluene and chloroform – two conventional solvents that are commonly employed in [3 + 2] cycloaddition reactions were calculated with ProTox 3.0 (a webserver for the

• , the conventional solvents that are typically employed as reaction media encompass a range of options, including tetrahydrofuran (THF) (a problematic solvent, p), dioxane (considered hazardous, h), benzene (designated as highly hazardous, hh), toluene (p), chloroform (hh), acetonitrile (p), sulfolane

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

• synthesis [Pd(OAc)2, t-Bu2MePHBF4, Cs2CO3, and CsOPiv in toluene at 130 °C] was utilized to afford the C–H arylation in 78% yield with a 1:4 ratio of 68/69 [36]. Subsequent reduction of the pyridine N-oxide with Pd(OH)2/C and H2 followed by acidic Boc removal completed their total synthesis of complanadine

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

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• conditions. Finally, we were able to achieve the Fischer cyclization of compounds 7a–j by using p-toluenesulfonic acid monohydrate as catalyst in boiling toluene (method A, step 2) [26][27]. On the other hand, the one-pot synthesis of target compounds 3a–j starting from hydrazino derivatives 5a,b was

• 1) afforded hydrazones (E)-9a,b. According to LC–MS, only the (E) isomers were present in the reaction mixtures and in the crude products. Hydrazones (E)-9a,b were then cyclized by refluxing in toluene in the presence of p-toluenesulfonic acid monohydrate (method A, step 2). It is noteworthy that

• C17H18N4O2S, 342.1156; found, 342.1151. General methods for the synthesis of compounds 3a–j and 10a,b. Method A, step 2 [26][27]: A suspension of the corresponding crude hydrazone 7 or 9 (100 mg) and p-TsOH monohydrate (1.80 equiv) in toluene (1 mL) was refluxed until the starting material was consumed. Then

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

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• precipitation from non-polar solvents such as hexane and toluene did not lead to a complete separation of quinoxalinones 9 and Ph3PO. We attribute this to the ability of Ph3PO to form a strong hydrogen bond between the phosphoryl oxygen and a proton from the donor group of the second molecule [56][57][58], in

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• employed including carboxylic acids [37], xanthates [38], electron-rich toluene or heteroatom-substituted species [39][40][41][42], organoboron compounds [43][44] and organosilanes [43][45]. Moreover, three-component radical relay processes employing styrene derivatives have also been widely studied. In

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

• . 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

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• . Synthesis of N-doped macrocycles MC1, MC2, and MC3. Reaction conditions: a) Pd2(dba)3, Pt-Bu3·HBF4, NaOt-Bu, toluene, 110 °C, 24 h. 3a: 16%; 3b: 10%. b) Pd(OAc)2, PMe(t-Bu)2·HBF4, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), DMAc, microwave, 170 °C, 5 h. MC1: 5%; MC2: 90%; MC3: 85%. Supporting Information

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• leaving group and activated, electron-poor dipolarophiles has been reported [31][32]. Treatment of aldehyde 4 with hydroxylamine in toluene at 60 °C for 1–3 h resulted in loss of the aldehyde as judged by 1H NMR spectroscopy of the crude mixture. When this was carried out in the presence of N

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

• molecule, yielding BMN as the final product (Scheme 1B) [49]. In the initial trial, 12 mol % of the MOF catalyst was added to a vial containing benzaldehyde, malononitrile, toluene as solvent, and dodecane as internal standard, and the reaction was shaken at 50 °C. Aliquots were collected at 30 minutes

• increases the rate of the condensation reaction. Thus, we initially supposed that, though dodecane was only 5.6 vol % to toluene, its addition was decreasing the difference in lipophilicity between the MOF and the bulk solution, reducing the driving force to remove water from the MOF pores. When we compared

• reaction mixture. To address both concerns of performing the neat Knoevenagel reaction – product precipitation and the incomplete submersion of the MOF catalyst – we reduced the catalyst amount to 1.5 mol %. Surprisingly, the reaction conversions were higher than those in toluene with 12 mol % catalyst

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

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ]. However, under the same coupling conditions (Pd2(dba)3, P(o-Tol)3, n-Bu4N+OH−, toluene/H2O, 90 °C), the reaction of diiodide 1 with bisboronic acids 75/6/7/8 gave only low yields of the desired macrocycles Me-M1 (7/32/22/21% for Me-M15/6/7/8). Thus, the macrocyclization via two-fold Suzuki coupling was

• routes towards macrocycles featuring one BINOL unit. a) Two-fold Suzuki coupling and b) two-fold Williamson synthesis. Reagents and conditions: i) bis(boronic ester) 75/6/7/8 (1.0. equiv), Pd2(dba)3 (0.1 equiv), P(o-Tol)3 (0.2 equiv), n-Bu4N+OH− (3.2. equiv), toluene/H2O 5:1, 90 °C; ii) ethylene glycol

• shown. Initially attempted route towards bis-BINOL macrocycles based on precursors Me-36 or Me-46. Conditions: i) 96 (2.2 equiv), Pd2(dba)3 (0.1 equiv), P(o-Tol)3 (0.2 equiv), n-Bu4N+OH− (3.2 equiv), toluene/H2O 5:1, 90 °C; ii) 96 (2.2. equiv), Cs2CO3 (3.0 equiv), CH3CN, 80 °C. Synthetic route towards