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

• 1,1-dioxide structural element. Results and Discussion We synthesized target compounds 3 exhibiting new tricyclic (3a–c, 3f–h, Scheme 1, Table 1) and tetracyclic (3d,e,i,j) ring systems starting from 8-chloro-2,4-dimethyl-2H-1,2,3-benzothiadiazine 1,1-dioxide (4a) and 8-chloro-2-methyl-4-phenyl-2H

• were previously used for the synthesis of 7-nitroindole derivatives: heating in polyphosphoric acid (PPA) at 80 °C [24][25]. However, our attempt was not successful. Experiments with zinc chloride, the most commonly used Lewis acid catalyst in Fischer indole syntheses, also failed under various

• performed using the method described in the literature [18], i.e., by heating compounds 5a,b with ketones 6a–e in the presence of bismuth nitrate pentahydrate catalyst and PPA in methanol at 110 °C in a closed vial (Scheme 1, method B). In the synthesis of asymmetric hydrazones 7a,c,f,h, the major product

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

• conjugates (S)-2a–e in CH3CN. The UV and CD spectra of the previously reported conjugates were measured in various polar and non-polar solvents, but the intensities and shapes were almost unchanged [41]. The conjugates (S)-2a–e are composed of two methoxy-biphenyl chromophores connected with a C–C single

• derivatives [41] the preferred conformation of (S)-2a can be proposed (Figure 2). In the case of the P conformer, a Newman projection along the C–N bond reveals that the bulkier substituent, the hydroxymethyl group (denoted as L), is close to a seven-membered ring, and is destabilized by steric repulsion with

• of all local minima employing DFT at the B3LYP/6-31G* level of theory [47]. Four low-energy conformers of (S)-3a were identified within 10.0 kJ/mol (Figure 3). Among them, conformers A and D exhibited an M twist between the long axes of the biphenyl chromophores, whereas conformers B and C displayed

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• ), tert-butyl isocyanide (3a), and TMSN3 (4) in 2 mL of MeOH. After heating the reaction mixture at 40 °C for 12 h, the solvent was removed and changed to 2 mL of MeCN followed by heating at 130 °C for 2 h (Scheme 3A). However, no desired product was detected in the reaction mixture. The functional groups

• introduce reactants in a sequential manner. Thus, we changed the reaction conditions by first reacting 0.2 mmol each of 1a and 2a in 2 mL MeOH at 40 °C for 40 min to form the Schiff base Int-I followed by the addition of 0.2 mmol each of 3a and TMSN3 (4) to obtain the desired 1,5-DS-T 5a as Ugi–azide adduct

• . After evaporation of the solvent MeOH, the residue was redissolved in 2 mL of MeCN and heated at 130 °C for 2 h in a sealed vial to give product 7a in 90% yield after purification via Cu-free intramolecular click reaction (Scheme 3C) [46]. This Cu-free intramolecular cyclization provides key practical

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• Lifen Peng Ting Wang Zhiwen Yuan Bin Li Zilong Tang Xirong Liu Hui Li Guofang Jiang Chunling Zeng Henry N. C. Wong Xiao-Shui Peng Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of

• -involved ureas, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines as well as C–H indolization of 2-alkynylanilines with 3-functionalized indoles. Isoindolones were synthesized successfully by electrochemical annulation of

• used as an inhibitor of cyclin dependent kinase (CDK8) [31]. Sulfonamide-N-benzoxaborole analog GSK8175 is an inhibitor against hepatitis C virus (HCV) [20] (Figure 1). The construction of five-membered rings obtained growing attention [32][33][34][35][36][37][38], and alkynes [39][40][41][42][43][44

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

• catalysts including Ni/CeO2-γAl2O3, spinal NiAl2O4 and Ni/La2O3-αAl2O3, at 230 °C and 3.2 MPa. Using a chiral catalyst composed of [RuCl2(benzene)]2 and SunPhos, an effective asymmetric hydrogenation of α-hydroxy ketones was reported, yielding chiral terminal 1,2-diols in up to 99% ee. This Ru-catalyzed

• -proline as a catalyst (Scheme 25) [100]. The C–C-bond formation between biomass-based feedstock by aldol condensation reactions of furfural with 1-hydroxyacetone has been reported by Subrahmanyam and co-workers (Scheme 26) [101]. C4 biobased carbonyl platforms Acetoin Acetoin is a very important C4

• 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

• , (−)-glaucopine C, and (+)-allocyathin B2 The cyrneine diterpenoids represent an important subfamily of cyathane diterpenoids which possess a common 5-6-7 fused tricarbocyclic core with two all-carbon quaternary stereocenters. Many impressive syntheses have been reported to date [18][19][20][21][22][23][24][25

• ][26][27][28][29][30]. In 2018, the group of Han accomplished the total synthesis of (+)-cyrneine A (7), (−)-cyrneine B (9), (−)-glaucopine C (10), and (+)-allocyathin B2 (8) by a collective manner [31]. In their synthetic route, an enzyme-catalyzed desymmetric enantioselective reduction of 1,3

• (9). Secondly, a based-mediated concomitant double bond migration and deacetylation, and selective oxidation of allylic primary alcohol accomplished the total synthesis of (−)-glaucopine C (10). On the other hand, Barton–McCombie deoxygenation and isopropylation of 43 produced ketone 52. Subsequently

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• . The former was demonstrated by the synthesis of alkaloid 14-epi-isochaetominine C that was used to determine the enantiomeric excess of the synthesized natural product (98.7% ee), while the latter was illustrated by the synthesis of both enantiomers of the alkaloid isochaetominine. Additionally, the

• reported structures of alkaloids aspera chaetominines A and B have been synthesized. Moreover, the four-step synthesis of the reported structure of aspera chaetominine B generated another diastereomer that was converted in one-pot to (–)-isochaetominine C, which turned out to be the revised structure of

• Aspergillus nidulans [24]; 3) (–)-isochaetominines A−C (4 - 6) and (+)-14-epi-isochaetominine C (7), isolated from the solid-substrate culture of an Aspergillus sp. Fungus [25], and from other sources for (–)-isochaetominine C (6) [26][27][28][29]; 4) isochaetominine (8) from Aspergillus fumigatus, an

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• Street, Moscow 11991, Russia 10.3762/bjoc.21.161 Abstract Indolo[1,2-c]quinazoline derivatives have emerged as promising chemotype in drug discovery due to their versatile biological activities, including antimicrobial and antiviral properties. In this study, we report the design, synthesis, and

• biological evaluation of novel indolo[1,2-c]quinazoline derivatives, with a particular focus on their antiproliferative potential against human cancer cells. We introduced structural modifications at positions 5, 6, and 12 of the indolo[1,2-c]quinazoline core to explore the structure–activity relationships

• polycyclic structures, DNA was not the primary target for their antiproliferative effects, as confirmed by FID assay and fluorescence titration studies. This study represents the first comprehensive evaluation of indolo[1,2-c]quinazolines as potential scaffold for the development of antitumor agents

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

• reported. A bioinspired approach represents many advantages to bring benefits to total synthesis. It could rapidly achieve complexity of the target molecule from a much simpler precursor in diverse forms of transformations such as cascade reaction, cycloaddition, and C–H functionalization, thereby, shorten

• propose the biosynthetic pathway, which has not yet been reported in Duh’s isolation report (Scheme 1a). In our proposal, the linear sesquiterpenoid trans-nerolidol (1) with a chiral tertiary alcohol undergoes dihydroxylation to generate triol 2, which further proceeds a C–C bond cleavage to afford

• evidences of chemical transformations. Thus, a bioinspired total synthesis was investigated (Scheme 1b). Synthetically, we did not start from trans-nerolidol (1) to construct a C–C bond cleavage. Instead, a convergent coupling approach was selected to quickly access the aldehyde precursor. Phenyl sulfide 5

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• light-harvesting carbazole units with photoresponsive azobenzene units in a unique macromolecular architecture (Figure 4c) [48]. The resulting cross-linked polycarbazole structure led to a high solar thermal storage capacity of 179.9 J/g and an extended half-life at 60 °C, increasing from 7 min for the

• azobenzene small molecules into polymer fibers [65], enabling solvent-free charging and discharging under visible light (Figure 6a). This material exhibited good capacity for releasing high-temperature heat (80–95 °C) at room temperature and in cold environments, along with an energy storage lifetime

• charged solar thermal fuels for deicing tests [74], showing effective ice removal capability under green light irradiation (Figure 7a). Wang et al. developed a photostimulated self-heating wristband [94] that elevates surface temperature from 29 °C to 44 °C upon blue light irradiation, protecting users

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• at reflux in acetic acid for 3 h for aminotriazole 1a or in n-BuOH for 7 h in case of aminotriazole 1b led to the formation of oxygen-bridged 2-(methylthio or methoxy)-11,12-dihydro-5H-5,11-methanobenzo[g][1,2,4]triazolo[1,5-c][1,3,5]oxadiazocine-5-carboxylic acids 4a–j (Scheme 2, Table 1). It should

• trace amounts of Schiff bases between amino-1,2,4-triazole and salicylaldehyde as well as with impurities of the reagents. This is most likely due to the electron-withdrawing nature of the substituent at C(3) in these 5-amino-1,2,4-triazoles that do not favor the proceeding of the MCR in contrast to 5

• -aminotriazoles 1a,b having pronounced electron-donating substituents (methylthio- and methoxy groups). On the other hand, the MCR of the reagents 1a, 2a–c and 3 under ultrasonic irradiation for 2 h at room temperature (25 °C) (Scheme 3) afforded a mixture of 5-(2-hydroxyphenyl)-2-(methylthio)-7-((3-(methylthio

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

• -ketoglutaric acid in the four-component Ugi reaction with equimolar amounts of the reagents. It was found that stirring of aromatic aldehydes 2a–d, aromatic amines 3a–d, KGA (1) and tert-butyl isocyanide (4) (in a 1:1:1:1 molar ratio) in methanol for 24 hours at 45 °C resulted in the formation of 5-((aryl)(1

• isocyanide (4) in a molar ratio of 1:2:2:2 in MeOH and subsequent stirring at a temperature of 45 °C for 24 hours led to the formation of N1,N5-bis(2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-N1,N5-bis(4-chlorophenyl)-2-oxopentanediamide (6a) in 55% yield (Scheme 2, pathway B; Table 2). Compounds 5

• contain a free carboxyl group and thus can also be used as an acidic component in the Ugi reaction. Indeed, it was established that the reaction of 5-((2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)(4-chlorophenyl)amino)-4,5-dioxopentanoic acid (5a) with aldehydes 2a,c, amines 3a–c, and tert-butyl

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• calculations have provided valuable insights into the photochemical stereoselectivities of cyclic azoalkenes. In 1998, Yamamoto and co-workers investigated the reaction paths for α-C–N and β-C–C bond cleavage during the direct and sensitized photolysis of DBH [81]. The minimum energy geometries in S0, S1, T1

• , and T2, conical intersections, transition structures, and singlet–triplet crossing were computed using CASSCF(10,8)/6-31G(d)//MP2/6-31G(d) [81]. The results suggested a stepwise C–N bond breaking with the formation of the diazenyl diradical intermediate [81]. In 2003, Olivucci and his co-workers

• inverted housane [83]. Chen and Li explored the potential energy surfaces and surface crossing points of 2,3-diazabicyclo[2.1.1]hex-2-ene with CASPT2(12,10)/6-31G(d)//CASSCF(12,10)/6-31G(d,p) in 2006 and concluded that on the S1 surface one C–N bond is broken [84]. In 2011, Abe and co-workers investigated

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• molecule is characterized by the absence of mirror planes and centers of inversion. Central chirality arises when four distinct substituents (a, b, c, and d) are arranged tetrahedrally around a central atom (Scheme 1A). Non-central chirality – such as axial and planar chirality – are becoming increasingly

• can be generated from achiral starting substrates by various means that assemble the four distinct substituents (a, b, c, and d) (Scheme 1D). In the case of central chirality, the differentiating substituents are often directly attached to the newly formed stereocenter. By contrast, for non-central

• chirality, the pairs of substituents (a and b, c and d) are separated in space because the stereogenic scaffolds span multiple atoms. Consequently, bond cleavage and formation occur at positions that are distant from the stereogenic elements and remote from the actual points of differentiation among the

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• [14]. Interestingly, this also works for terminal alkynes, which are typically known to undergo direct C(sp)–H arylation instead [15][16]. In the context of 1,2-carbofunctionalization, terminal alkynes are more scarcely studied. Among those few examples is a trifluoromethylative thiocyclization

• on intermediate allyl cation (Scheme 1C). The obtained tetrahydrofuran and pyrrolidine derivatives with highly substituted vinyl side-chains are regarded as privileged structures in medical chemistry [23][24]. Moreover, the resulting styryl functionality (Ph-C=C-) is often found in drug molecules as

• )dimethylsilane (7a) – and analogous aliphatic chain-containing propargylsilanes 7b,c were obtained from the commercial hept-1-yne [26]. While searching for appropriate arylation conditions (Table 1, entry 1) we observed the formation of both the arylated diene 10a and silylindene 11a (≈75:25). Both products are

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

• catalytic photoenolization/Diels–Alder (PEDA) reaction [14][15]. In this process, the NHC fragment present in the acylazolium species influences the absorption wavelength and fundamental photochemical reactivity of the C=O bond, enabling a “ketone-like” photoreaction from otherwise unsuitable carboxylic

• species C benefitting from additional stabilization by virtue of electron delocalization onto the NHC-derived azolium ring [17][18][19][20]. Similarly, the cationic azolium fragment in acylazolium salts can effectively lower the carbonyl reduction potential relative to the starting material with single

• -electron reduction delivering the same stabilized radical C. Beginning with a seminal report by di Rocco and Rovis in 2012 [21], the combination of NHC and photoredox catalysis has recently been the subject of intense research activity [22][23][24][25][26][27][28][29][30]. Employing the latter reductive

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

• synthetically challenging because of the tricyclic ring system, spiroketal moiety (B, C-ring), and instability arising from dehydration of the hydroxy groups. Prior approaches to (±)-4 have shown the feasibility of accessing this target molecule. Blair [7] and Sulikowski [8] reported the total synthesis of

• was initially investigated (Scheme 3). Chan’s diene (16) was subjected to condensation with freshly distilled aldehyde 17 in THF at room temperature, using a catalytic system comprising Ti(OiPr)4/(S)-BINOL complex (2.0 mol %). Subsequent deprotection with pyridinium p-toluenesulfonate (PPTS) at 0 °C

• reaction at 50 °C for 36 h, and extensive decomposition of the starting material β-keto ester 15 occurred (Table 1, entry 1). Solvent screening of EtOH [26], acetic acid [26], and hexafluoroisopropanol (HFIP) [27] demonstrated that HFIP afforded optimal results, delivering cyclopentanone 14 in 63% yield as

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

• underwent a reductive interrupted Fisher indolization with phenylhydrazine to give indoline 281. To forge the C16 stereocenter and form the C–O bond at C2, diol 282 was prepared from 281 in six steps. Treatment of 282 with MeI/Cs2CO3 induced cyclization through putative indoleninium intermediate 283

• leustroducsin B (96). Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109). Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116). Ōmura’s synthesis of salinosporamide A (125). Kang’s synthesis of ʟ-cladinose (124) and its derivative. Kang’s preparation of fragment

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

• -substrates with the potential to react with metal carbenoids in many different ways [14], for example through O–H, N–H or formal C–H insertion, cyclopropanation, or oxazole [20] formation. The 16 co-substrates, selected from available compounds in our laboratory, are shown in Figure 2 (panel A). Many of

• these substrates had more than one potentially reactive site to enable, for example, O–H insertion (C1–5, C8, C11 and C14), N–H insertion (C3, C6, C12, C13 and C15), formal C–H insertion (C1, C3, C4, C12, C15 and C16), oxazole formation (C9 and C10) and cyclopropanation (C7, C10, C14 and C16). To start

• amine (→ 4-18); cyclopropanation (→ 2-7); and formal C–H insertion into an indole (→ 1-15a and 2-15a) or naphthol (→ 2-4 and 3-4b). In the case of 4 (2-naphthol) and 15 (5-methoxyindole), co-substrates containing functional groups with more than one potentially reactive site, two regioisomeric products

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

• through circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopy. Results and Discussion The syntheses of N-doped macrocycles MC1–3 are shown in Scheme 1. Diamines 1a and 1b were synthesized by double Pd-catalyzed C–N coupling reaction of 4,6-dichlorobenzene-1,3-diamine with phenyl

• could be viewed as the aza[14]metacyclophane derivatives, in which two benzene rings are replaced by two pyrenes. The Pd-catalyzed arylation of 3a with Pd(OAc)2, PMe(t-Bu)2·HBF4 and DBU under microwave conditions gave two isomeric macrocycles MC1 and MC2 with four newly formed C–C bonds in yields of 5

• % and 90%, respectively. For MC2, four C–C bonds are formed between the dichlorobenzene units and tert-butylphenyl groups, generating two dihydroindolo[2,3-b]carbazole subunits. In contrast, there is only one newly formed C–C bond between the dichlorobenzene unit and one pyrene moiety for MC1

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 5% fetal bovine serum (FBS), 1 mM ʟ-glutamine, and antibiotics (penicillin 5,000 U/mL and streptomycin 5,000 µg/mL). Cells were incubated at 37 °C in a humidified atmosphere with 5% CO2. For cytotoxicity assays, cells were seeded into 96

• a final concentration of 0.5 mg/mL. Plates were incubated for 3 hours at 37 °C in a CO2 incubator to allow for formazan crystal formation. Subsequently, 150 μL of dimethyl sulfoxide (DMSO) was added to each well to solubilize the formazan. Plates were shaken for 15 minutes, and absorbance was

• (O)Cl3 and glycidol were purchased from suppliers and used without additional purification. Synthesis of diglycidyl methylphosphonate (1). A 500 mL flask with 200 mL of dichloromethane, equipped with a mechanical stirrer, was cooled to −30 °C. Then, 2 equiv of glycidol (21.4 g, 0.289 mol) and 4.2

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• tetrasubstituted piperazines 2b–j were obtained as a single, enantiopure diastereoisomer from diimines 1b–j, prepared from the enantiopure trans-1,2-diaminocyclohexane and aromatic aldehydes, in good to excellent yields. Substrates bearing electron-withdrawing groups such as trifluoromethyl (2b,c) and bromine (2d

• mmol, 3 equiv) were then added to the electrochemical cell. The reaction mixture was degassed by bubbling with argon for 20 minutes under vigorous stirring. The undivided cell was then connected to the Autolab power supply and stirred at 25 °C under galvanostatic conditions at 5 mA (2.5 mA/cm2) until a

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

• rate of evaporation from a nanolitre solution of analyte encased within oil [33], suitable single crystals were obtained. The X-ray analysis allowed the determination of the relative stereochemistry, as shown in Figure 2. Compound 5a crystallised as a racemic mixture in the space group P21/c. The major

• g, 1.3 mmol) was added to epoxide 1 [28] (2.2 g, 12.7 mmol) and allyltrimethylsilane (6.1 mL, 38 mmol) in dry MeCN (90 mL) at 0 °C. After 1 h, saturated aqueous NaHCO3 (50 mL) was added, and the mixture was extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (20 mL

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

• for interconversion. However, steric repulsion between the C-1 substitutions and the terminal arene moieties in the M-conformational diastereomer resulted in the P-conformational diastereomer being thermodynamically favored. This led to the formation of (P)-helicene products following DDQ-mediated

• enantioselectivity, with an s-factor up to >259 (Scheme 7). Notably, this reaction did not produce the typical arene C–H amination products but instead the dearomative amination products 26, which is believed to be due to the significant steric hindrance surrounding the amination site that impeded the subsequent

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

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

• respective isocyanate in acetonitrile at 80 °C; KSU-1 reacted with isopropyl, tert-butyl, n-hexyl, and tetradecyl isocyanate to generate KSU-1iPr and KSU-1t-Bu, KSU-1n-Hex, and KSU-1C14, respectively. Successful post synthetic reaction was observed by proton nuclear magnetic resonance (1H NMR) spectroscopy

• 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

• , Supporting Information File 1). We found that the conversions were significantly better than those reported for H2BDC-NH2 under more forcing conditions (60 °C, 6 h) [52], which makes sense given that the methyl substituents on the carboxylate increase the basicity of –NH2, which should increase the catalytic