Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• ring skeletons with different stereochemical outcomes could be obtained due to the flexible conformation of this cyclodecadiene ring system [34][37][53][54]. To our delight, treatment of compound 5 with p-toluene sulfonic acid (PTSA) delivered the desired trans-6/6-fused ring system, via its favored UU

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• ); unreactive substrates are shown in Supporting Information File 1, Schemes S4 and S5. Benzene, toluene, tert-butylbenzene, biphenyl, naphthalene, o-xylene, and durene afforded the corresponding products 2–8 in moderate yields. In contrast, mesitylene, a less electron-enriched substrate than durene, gave

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• (Scheme 1). To support these working hypotheses, the reaction of 1 equiv [Cu(OH)(IPr)] with 2 equiv of formic acid in a sealed tube was followed by 1H NMR spectroscopy in deuterated toluene (C7D8). After 16 h at 110 °C, the formation of 1b was observed while no excess of formic acid was detected

• produced, the pressure change was measured as a function of time (see Supporting Information File 1, Table S1). By heating formic acid in toluene in the presence of 1 and 10 mol % of 1a, no evolution of gas was observed neither at 25 nor at 110 °C (see Supporting Information File 1, Table S1, entries 1–4

• our delight, upon reacting in toluene equimolar amounts of FA and PhSiH3, efficiency increased (Figure 2). Indeed, by using 1a and its tert-butoxide congener 1c ([Cu] = 10 mol %) a violent evolution of gas was observed at room temperature, resulting into a considerable increase of pressure which

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• means that an uncertainty of several kilocalories per mole is plausible for the less stable/transient subset. Consistent with this, Parker/Cheng highlight a higher uncertainty for the toluene/fluorene/9-methylanthracene-derived cations, and we observe that most of the large deviations occur in benzyl

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• . Synthesis of PROTACs towards FGFR2. Reagents and conditions: (a) K2CO3, Pd (dppf)Cl2, 1,4-dioxane/H2O 4:1, 100 °C, 5 h; (b) 3,5-dimethoxyaniline, Pd2(dba)3, BINAP, Cs2CO3, toluene, 100 °C, 12 h; (c) (2-bromoethoxy)-tert-butyldimethylsilane, NaH, DMF, rt, 12 h; (d) tetrabutylammonium fluoride, THF rt, 12 h

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• best among the solvents tested (EtOAc, toluene, methylcyclohexane, tetrahydrofuran, and methanol) (see Supporting Information File 1, Figure S5). The hydroxy moiety has a stronger interaction with catalytically active sites at the surface of the heterogeneous catalyst, and smooth desorption of the

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• -toluenesulfonic acid at 80 °C in toluene afforded benzoxocin (7) as the only product. On the other hand, melifolione A (1) was completely decomposed under these conditions. Irradiation of 5 in methanol with UV-light (300 nm) for 3 days at room temperature gave melifolione B (2) with traces of melifolione A (1

• dissolved in toluene (50 mL) and 4-toluenesulfonic acid (50 mg) was added. The mixture was heated under stirring on a water bath at 80 °C for 3 h. After cooling to room temperature, diethyl ether (100 mL) was added, and the organic phase was extracted with 0.1 N NaOH (3 × 30 mL). The alkaline aqueous layer

• /1 h/57%, d) p-toluenesulfonic acid/toluene/80 °C/1 h/68%. Reaction of melifolione A (1) with iodosobenzene diacetate. Hypothetical pathway for the oxidative ring contraction of melifolione A (1) with ferricyanide/hydrogen peroxide. Oxidative ring contraction of melifolione B (2). Alternative routes

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• , MeOH, rt; (b) i. NaH, BnBr, THF, rt; ii. iodobenzoic acid, MeCN, 80 °C; iii. PhOOSCH2PO(OEt)2, NaH, THF, 0 °C; (c) vinylmagnesium bromide, CuI, THF, −78 °C; (d) i. ethyl acrylate, Grubbs cat 2nd generation, toluene, 110 °C; ii. p-TsOH, H2O, THF, 60 °C; (e) NaH, THF, 0 °C; (f) i. LiAlH4, THF, 0 °C to rt

• ) i. AcOH, rt; ii. NaIO4, MeOH, 0 °C to rt; iii. NaBH4, MeOH, 0 °C to rt; iv. NaH, BnBr, 0 °C to rt; (c) i. O3, DCM, −78 °C; ii. SMe2; (d) (PhO)2POCH2COOMe, KHMDS, 18-crown-6, THF, −78 °C; (e) p-TsOH, toluene, H2O, 100 °C; (f) MOMCl, DIPEA, DCM, 0 °C to rt; (g) i. DIBAL-H, DCM, −78 °C; ii. Ac2O

• , pyridine, DMAP, DCM, rt; iii. allyl-TMS, BF3·Et2O, DCM, −78 °C; (h) 9-BBN, THF, H2O2, 0 °C to rt; (i) i. AD-mix β, MsNH2, t-BuOH, H2O, rt; ii. 2,2-dimethoxypropane, (±)-CSA, DCM, rt; (j) i. DMP, DCM, rt; ii. Ph3PCH2COOEt, toluene, rt; (k) p-TsOH, EtOH, reflux; (l) i. DBU, toluene, reflux; ii. TBAF, THF, rt

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• copper complex (although an extraction procedure for complex destruction using Na2S2O3 was applied), which was difficult to separate from the relatively polar free calixarene 37 using column chromatography. In line with this, when toluene-soluble CuI·P(OEt)3 was used as a catalyst (in this case heating

• presence of CuI using a mixture of toluene and triethylamine (4:1) as solvent. Under these conditions, the reaction proceeded smoothly at room temperature and the desired ditriazole 41 was obtained in high yield (Scheme 7). The tert-butoxycarbonyl groups in calix[4]arenes 37–41 were cleaved under standard

• . Synthesis of triazolated p-aminocalix[4]arenes 37–39 from the propargylated calixarene precursors 24–26. Conditions: i) benzyl azide, CuI, Et3N, toluene, rt. Synthesis of triazolated p-aminocalix[4]arenes 40 and 41 from the 2-azidoethylated calixarene precursors 35 and 36. Conditions: i) phenylacetylene

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• benzoylation of hydroxymethyl groups under the conditions of Sonogashira cross-coupling, nitroxide 2a was treated with acetic anhydride in the presence of sodium acetate, yielding the diacyl derivative 5. Radicals 5 and 3a were heated with benzoyl chloride and triethylamine in toluene in the presence of a

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• alcohols 1a–l participating in the reaction. Phytic acid has six phosphoric acid moieties, therefore we treated it as if it contained six moles of phosphate per mole of phytic acid. All diaryl phosphates were isolated as sodium salts through precipitation in toluene by neutralization with a NaOH methanol

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• mixture of hot toluene and hexanes. The efficacy of recrystallization was especially useful to our synthetic goal as it obviated the need to separate the mixture of regioisomers 3 and 7 from the nitration step, which were challenging to purify from each other. Product 6, which was isolated as an off-white

• recrystallization from toluene and hexanes. The two-step process of benzylic bromination and Kornblum oxidation of 3 to 4 was accomplished in 38% yield (37% if using the mixture of 3 and 7). This oxidation is not the highest-yielding method for this transformation, but it represents a concise, operationally simple

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• explored the use of alternative solvents while reducing the amount of methanol to 10 or 20 equivalents. Among the solvents tested, including THF, toluene, MeCN, and DCM (Table 1, entries 11–15), DCM performed best, affording the product in up to 65% yield (Table 1, entry 14). In contrast, significantly

• lower yields were observed in THF and toluene (Table 1, entries 11 and 12), likely due to poor miscibility or reactivity under the reaction conditions. These findings provide a useful basis for further extending the method to structurally more complex or less soluble alcohol substrates. With the

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