Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• compositions of antitumor antibiotics of the kigamycin family include the oxazolo[3,2-a]pyridine skeleton [55][56]. To obtain oxazolopyridones containing trifluoromethyl substituents, the syntheses have been proposed, which are based on the intramolecular cyclization of 1-phenyl-2-(4-(trifluoromethyl)piperidin

• imine reaction center. This makes the center softer, which favors the interaction with the amino group to generate the hexahydropyrimidine intermediate C. The methyl, ethyl and butyl substituents of intermediate B have a positive inductive effect, which increases with the lengthening of the alkyl chain

• piperidone ring, the chemical shifts of axial and equatorial shifts of methylene protons at C(9) are inverted and Δ9ea < 0 (see Table 4, Figure 4). In the 19F NMR spectra, the CF3 group of diastereomeric octahydropyrido[1,2-a]pyrimidinones 4att and 4atc, 4btc with the trans-configuration of the substituents

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• nature of para-substituents on the reaction mechanism. The substituents considered in the study include -OCH3, -SCH3, -Cl and -NO2 groups. For these chalcones, different possible pathways at various steps during the reaction are investigated leading to formation of α,β-ditosyloxy ketones and β,β

• -substituents; α,β-unsaturated carbonyl compounds; Introduction Hypervalent iodine compounds exhibit a range of bonding patterns which making these compounds powerful reagents or catalysts for a number of organic transformations [1][2][3][4] – oxidation of alcohols [5], epoxidation of alkenes [6], oxidative

• , however, a number of studies also report the formation of a carbenium ion as an alternate pathway, typically for the oxidation of alkenes with phenyl substituents on carbon–carbon double bonds [10][11][12][29][34][35]. Here, Scheme 1 depicts the reaction investigated in the current study which is, HTIB

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

• are easily separable by column chromatography due to their different polarity. Next, we investigated the substrate scope and limitations of the reaction using differently substituted iminopropargyl alcohols (Table 2). The presence of alkyl substituents in the hydroxy fragment was well tolerated

• alcohols with aromatic substituents 1d (R1 = Ph, R2 = Me) and 1e (R1 = R2 = Ph) were found to be less productive: the reaction required a 2-fold longer time (30 min) and resulted in lower yields of salts 2d,e likely due to side polymerization (Table 2, entries 3 and 4). At the same time, the yields of

• yield (59%) compared to 1a (Table 2, entry 7). Also, C3F7-iminopropargyl alcohol 1i was a suitable substrate giving the desired products 2i and 3i in 75% and 18% yields, respectively (Table 2, entry 8). Clearly, the results show that the substituents in the hydroxy moiety have a significant impact on

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

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

• Group, Magyar tudósok krt. 2, H-1117 Budapest, Hungary 10.3762/bjoc.21.205 Abstract New tetra- and pentacyclic derivatives of the dibenzo[c,f][1,2]thiazepine ring system have been synthesized. The target compounds contain methylenedioxy or ethylenedioxy substituents linked to the benzene ring. The key

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

• presence of the –OMe group (3p). Aldehydes with substituents in the meta-position also delivered excellent results (3q–s) and aldehydes with OR groups in the meta,para-position (3t, 3u) gave almost quantitative yields (up to 95%). Finally, the developed protocol was also shown to be effective for

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

• in organic solvents. Results and Discussion Decoration of silica gel with bambusuril For the modification of silica gel (SG), we selected previously reported bambus[6]uril BU1 (Scheme 1) containing 12 carboxyalkyl substituents [13]. This macrocycle was chosen for several reasons: BU1 can be attached

• minimal decomposition at temperatures below 800 °C as confirmed by the analysis. In contrast, a-SG, SG-NHCO-BU1, and SG-BU1 exhibited reduced thermal stability due to the presence of organic substituents (Figure 1A and Supporting Information File 1, Figure S1C). A weight loss of 10% for BU1, SG-NHCO-BU1

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

• -rich and electron-poor substituents. This reaction was carried out between arylcyclopropanes 5 and acyl fluoride 4 in the presence of NHC (10 mol %) and 4CzIPN (5 mol %). Mechanistic studies showed that the cascade proceeds via nucleophilic ring-opening of a cyclopropyl radical cation D with subsequent

• , various NHCs and photocatalysts were examined, and it was found that rhodamine 6G in combination with triazolium-based NHCs bearing mesityl substituents gave the best results compared to those bearing phenyl or pentafluoroaryl rings. Rhodamine 6G also offers the best outcomes compared to other

• /organophotocatalyzed oxidative Smiles rearrangement of O-aryl aldehydes 26 has been developed using oxygen as the terminal oxidant under visible-light dual catalysis. This approach afforded highly functionalized 2-hydroxyarylbenzoates 27, tolerating electron-deficient and electron-rich substituents. The C–O bond

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• introduction of diverse substituents at the C2 position and precise modulation of oxidation states at other sites, including C3. The synthesis of 3-epi-ryanodol (5) commenced with compound 44. After the protection of the C10 secondary hydroxy group, a sterically controlled, face-selective reduction of the C3

• effectively resolved a major obstacle in the synthesis of ryanodine (1) and established a versatile approach for introducing diverse C3 ester substituents for future SAR studies [49]. The synthesis commenced from advanced intermediate 71 (from their prior work). Sequential SeO2-mediated oxidation, triflation

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• stereochemistry of substituents, as well as the heterocyclic anomeric unit. Uncertainty regarding the mode of action, along with inadequate synthetic approaches toward a lead compound, remains elusive. The well-established synthetic route reported by Hanessian and co-workers began with ᴅ-ribonolactone which bears

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

• ). The proton signals of the NH₂ and CH₂S groups of the isothiouronium substituents were clearly observed at 9.04 ppm and 4.23 ppm, respectively. Additionally, the carbon signal of the CH₂S group appeared at 169.3 ppm. The NMR signals, consistent with a fully symmetric structure, evidenced the exhaustive

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

• benzyl halides and other electrophiles were used under optimal reaction conditions to obtain various 3-(alkylthio)thiophene-2,5-dicarboxylates. Among them, compounds 4b–g, bearing benzylthio substituents, were prepared using different benzyl-type alkylating agents. It was found that the reaction

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• the trifluoroacetimidate. We therefore decided to use the two-chamber method for the synthesis of a few non-carbohydrate acetimidates 8–11 (Figure 3). Hence a series of aryl alcohols with different substituents on the aromatic ring were synthesized and isolated in generally good yields. One exception

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

• van-der-Waals interactions between phenyl rings of the benzoate substituents are crucial for the stabilization of the furanoside isomer. This outcome could not be rationalized within the framework of conventional carbohydrate chemistry, as the key intramolecular interactions determining the

• 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

• -, arabino-, and xylo-. However, for both α- and β-mannosides, pyranoside form remains the favorable one. In another study [26] the presence of two bulky silyl substituents (TIPS or TBDPS) at the O2 and O3 positions of galactose also resulted in stabilization of the furanoside product (Figure 2C). Another

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• was employed as an additive and mesitylene served as the solvent. The reaction was conducted at 60 °C under an argon atmosphere. When 1-(naphthalen-1-yl)benzo[h]isoquinoline derivatives bearing various substituents were used as substrates, the reaction proceeded efficiently, yielding the products 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

• aromatic aldehydes exhibit a Z-configuration [112][113] and it appears that endo-coupling of the Z-configured C,N-diphenylnitrone with maleimide is more favorable. Indeed, the distribution of the cis/trans product is also found to be significantly influenced by the nature of the substituents present in the

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• desired reaction [17]. Under these conditions, the reaction was performed on a 5 mmol scale without any loss of efficiency. We next evaluated the scope of the developed protocol. The electronic and steric nature of substituents had a minimal impact on the product yields and in most cases, the desired

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

• efficient iodide recognition and suggests possible applications in environmental monitoring, particularly for detecting radioactive iodine species in nuclear waste streams. Additionally, the cavity size of the macrocycle can be precisely modulated by varying the number of bridging benzene substituents

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

• in four steps. Subsequent conjugate addition of the lithium anion of TMS-acetonitrile to 15, followed by careful one-pot protonation of the resulting enolate with ethyl salicylate and TMS removal with CsF, gave 16 bearing three properly arranged substituents. Grignard 1,2-addition to ketone 16

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

• also observed in Yang’s total synthesis of (+)-cyclobutastellettolide B (13) as described above [21]. The driving force for the rearrangement is proposed to stem from 1,2-strain between the substituents at C13/C10 and C13/C7, consistent with observations from Yang's work [21]. Next, peroxides 54a and

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

• along with comparator H2 as solid-state sequestrants for a panel of five dyes (methylene blue, methylene violet, acridine orange, rhodamine 6G, and methyl violet 6B). We find that catechol-walled H2 (OH substituents) is a superior sequestrant compared to G2W1–G2W4 (OMe substituents). X-ray crystal

• substituents – performs significantly better than G2W2 and displays very good removal efficiency for methylene violet. Previous researchers have shown that dye adsorption is promoted by hydroxy, carbonyl, methoxy, and aldehyde substituents which provides an explanation for the better performance of G2W1

• relative to G2W2 [48]. Quite surprisingly, the removal efficiencies for H2 are notably higher than G2W4 for all five dyes studied. These differences are particularly noteworthy given that H2 and G2W4 are constitutional isomers and differ only in the swapping of methoxy substituents (G2W4) for hydroxy and

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

• tolerated a range of substituents on the olefin, giving the products with high enantioselectivity. Reactions of chiral β-methyl-substituted aldehydes 11 and 12 with indene (13) yielded tricyclic products with good diastereoselectivity and particularly high optical purity (99% ee). Organo-SOMO catalysis was

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

• substituents serve as critical switches for determining reaction pathway selection. Chemists have developed sophisticated synthetic strategies for programmable assembly of complex small molecular framework by leveraging substituent electronic and steric effects. In 2006, the Shibata group reported a gold

• under gold(I) catalysis through a substituent-controlled strategy (Scheme 8) [15]. Substrates with heteroaryl substituents underwent 6-endo-dig cyclization via gold-heteroatom coordination, furnishing the lactone-fused pyran scaffold 34 (Scheme 8, path a). Substrates with aryl substituents at the

• al. (Scheme 11) [18]. The pathway selectivity was regulated by modulating substituents on the terminal alkyne. When the alkyne was unsubstituted, the vinylidene intermediate 48 was generated via a 5-exo-dig cyclization, which subsequently underwent protonolysis to yield the bicyclo[3.2.1]oct-2-ene

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• contrast to classic Buchwald–Hartwig couplings – aryl bromides with substituents at the ortho-position (3a and 3c–g) are more reactive than those with substituents at the para-position (3b and 3h–l). This difference might be explained by steric repulsion, which may favor C–N-bond coupling with the terminal

• efficiency, as the reaction proceeds smoothly even when both coupling partners possess sterically hindered substituents at the 2,6-positions. For example, the coupling of 2,6-difluorophenylhydrazine with 1-bromo-2,6-dimethoxybenzene yielded tetra-ortho-substituted azobenzene 5a in a notable yield of 63

• )–aryl intermediate (B). Subsequently, ligand exchange occurs, generating hydrazido complexes C and C'. When bulky substituents are present on the phosphine ligand and/or (both) coupling partner(s) has ortho-substituent(s), the hydrazido complex C, chelating on the terminal nitrogen, is preferentially

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• , empirical approaches based on 1H NMR anisotropy method have gained attention as alternative strategies for stereochemical assignment of chiral molecules. Among these, the modified Mosher method, which utilizes the ring current effects of aryl substituents, has been extensively applied to chiral alcohols [2

• )-2a. This inversion of Cotton effects is due to the difference in steric features between the two substituents of amines: methyl and hydroxymethyl group in (S)-2a, and isopropyl and hydroxymethyl group in (S)-2b. The CD spectra of 1–(S)-2-phenylglycinol conjugate (S)-2c showed the same sign for the

• reasonably predicted by simply evaluating the relative steric bulkiness of substituents near the amine moiety. The relative substituents’ priority is determined not by the CIP rule, but by the steric bulkiness of substituents. On the other hand, for quaternary amines, it was difficult to assess the relative