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

• mechanism involving the participation of ethylenediamine (EDA) is shown in Scheme 4. Initially, the basic EDA is protonated by acetic acid (AcOH), forming ethylenediamine diacetate (EDDA) in situ. The use of EDDA has been reported as a highly efficient catalyst for the synthesis of 5-arylidene-2,4

• % of EDDA at 80 °C for 30 minutes under microwave irradiation. Despite this later methodology looks very efficient, the method reported here enables the in situ generation of the catalyst, allowing for an expanded reaction scope with 2,4-TZD derivatives (23 examples) and also proving effective for

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

• then converted to vinyl iodide 26 via hydrazine formation followed by iodination using Barton’s method. Subsequent Bouvealt aldehyde synthesis and in situ reduction delivered allylic alcohol 27. Epoxidation of 27 with m-CPBA afforded the rearrangement precursor 28. Protonic acid-promoted semipinacol

• deprotection and oxidation of the secondary alcohol, yielded the cyclization precursor 35. A B(C6F5)3-catalyzed tandem Nazarov/ene cyclization of 35 provided the key spirocyclic intermediate 37. The tertiary alcohol was protected in situ with TESOTf to suppress retro-aldol side reactions. Notably, prior TES

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

• reported the first total synthesis of ryanodine from ryanodol [47] (Scheme 5). Their strategy utilized a novel boronate protecting group to mask the four syn-oriented hydroxy groups. A critical step was the in-situ generation of the pyrrole-2-carboxylate unit from a glycine ester and 1,3-bis(dimethylamino

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

• asymmetric conjugate addition was carried out [20][21]. The in situ generated aryl–copper(I) species was obtained under the action of CuBr·Me2S with Grignard reagent 8, and then added to a THF solution of the α,β-unsaturated acyl oxazolidinone 7 at −48 °C. This reaction demonstrated an excellent

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

• NaClO·5H2O, the in situ-generated nitrile N-oxide immediately underwent intramolecular dipolar cycloaddition to deliver the cycloadducts 18 in good yield as a mixture of two inseparable diastereoisomers. This telescoped step was readily performed on a gram scale without interrupted purification of the

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• synthesis of aniline 10 and carboxylic acid 13. To access 10, the isoorotic acid derivative 6 was treated with oxalyl chloride to form the corresponding acyl chloride in situ which was then slowly added to a solution of m-phenylenediamine (9) to afford the target aniline in 62% yield (Scheme 2). Slow

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

• of the S–S bond in disulfide 3 followed by in situ alkylation was investigated for the one-pot synthesis of 3-alkylthio-substituted thiophene-2,5-dicarboxylates. We first focused our efforts on optimizing the conditions of this two-step process to determine suitable reducing agents and solvents

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• a six-membered palladacycle intermediate 9. Subsequent reaction with in situ-generated HNO3 facilitates nitro group incorporation to form the C1-nitrated carbazole product 2a and regeneration of the active palladium catalyst 7, thereby completing the catalytic cycle. Conclusion In summary, we have

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

• have been little studied, and are of interest to synthetic chemists. Thus, the interaction of (−)-metaphanine (70) with ammonia in CH3OH at room temperature led to the in situ formation of imine 72, which, as a result of an intramolecular aza-benzilic acid-type rearrangement, was converted in more than

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

• 1,3-diol intermediate was transformed into acetonide 25 (Scheme 5). Subsequently, the desired five-membered ring was successfully constructed through the in situ-generated alkylidene carbene 26 followed by C–H insertion; herein lies a significant electronic effect influencing this crucial step. With

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

• in-situ generation of toxic 1O2. Fumaramide Fumaramide is a bisamide photoswitch with a thermally stable trans-olefin, which, upon UV light irradiation, undergoes trans-to-cis isomerization, affording the corresponding maleamide (Figure 2). These photoswitches are distinct due to their ability to

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

• , enabling the total synthesis of 13 via in situ intramolecular lactonization as a key step. Computational and experimental studies reveal that the regio- and stereoselectivity of the Norrish−Yang cyclization are governed by the influence of the methyl group at C10: (1) In terms of regioselectivity, the 1,3

• blue LEDs at room temperature constructed a single diastereoisomer 23 in 90% yield. From 23, the ABCDE pentacyclic skeleton of phainanoids (27) was ultimately established via a Mitsunobu reaction, intramolecular nucleophilic substitution with in situ-generated aryllithium, and protecting group

• protection as ketal and nitrile reduction. The two building blocks (76 and 81) were then merged through the desired formal [3 + 3]-cycloaddition to generate N-desmethyl-α-obscurine (82), presumably via in situ-generated intermediates 76a and 81a, respectively. Subsequent Boc protection of the cyclic amine in

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

• species in situ was crucial for this transformation. By modifying a procedure for the trifluoromethylation of ketene dithioacetals reported by Liu and co-workers using TMSCF3 [43], rapid consumption of enamine 15 was observed. Acidic treatment of the intermediate promoted the hydrolysis/elimination

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

• and hydrogen elimination then occurred, affording 3-azabicyclo[4.1.0]hepta-2,4-diene derivatives 156. In contrast, when the temperature was raised to 110 °C, intermediate 155 underwent a 6π electrocyclic ring-opening, which was trapped by in situ-generated cyanide ions to form 4,5-dihydro-3H-azepines

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

• proposed. In the first step a C–N-coupling reaction with phenylhydrazine occurs [57]. The catalytic cycle starts by the formation of Pd(0) in situ through reduction facilitated by phosphine and water [58]. This is followed by the oxidative addition of aryl bromides, leading to the formation of the Pd(II

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

• derivatives 10a,b exhibiting an extended aromatic ring system were isolated instead of the expected primarily formed congeners 11a,b, due to in situ oxidation of the C–C bond. Alternatively, when the one-pot method (method B, bismuth nitrate pentahydrate + PPA, MeOH, closed vial, 110 °C) was applied for the

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

• ][254], this approach exhibited the following advantages like without metal catalysts and external oxidants, atom economy, facile access of starting materials, etc. In 2024, Cho succeeded in the preparation of trifluoromethylated oxazoles through in-situ aminotrifluoromethylation/cyclization of alkynes

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

• of Lewis acid–base bifunctional catalyst (Zr-β zeolite and K2CO3) in the Meerwein–Ponndorf–Verley reduction of a concentrated furfural solution (17.3–80.5 wt % in ethanol) combined with in situ cross-aldol condensation with acetaldehyde and crotonization. Ethanol was used as hydrogen donor for the

• Meerwein–Ponndorf–Verley reduction, while acetaldehyde is generated in situ by ethanol oxidation (Scheme 50). The equilibrium allows furfural to be simultaneously converted into furfuryl alcohol and 3-(2-furyl)acrolein in one pot through a redox reaction. The highest mass conversion rate of furfural can

• hydrolysis (Scheme 59). Furfural was employed as starting scaffold in a protocol developed to form acetals as fuel additives. The acyclic acetal is generated in situ from crude furfural with propanol in dimethyl carbonate using a nanoporous aluminosilicate material Al-13-(3.18) as catalyst, and then

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

• , protection of the resultant primary alcohol, and hydrogenation afforded ketone 65. The LaCl3·LiCl-promoted addition of 65 with Grignard reagent followed by TES protection of the resulting secondary alcohol, regioselective deprotection of the TES group and in situ oxidation provided aldehyde 66. Next, 66

• 77 and subsequent deprotection produced tertiary alcohol 78. Starting from this common intermediate, on the one hand, through successive manipulations by diazotization and in situ azide substitution, AgNO3-mediated aza-Cope/Mannich [62] reaction delivered ketone 79. Subsequently, a three-step

• operation including azide–alkene dipolar cycloaddition, irradiation of the resulting triazoline to aziridine 80 and in situ ring opening followed by deacetylation achieved the first total synthesis of (−)-hunterine A (14). On the other hand, aza-Cope/Mannich reaction of 78 produced imine intermediate 81

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

• synthesis of (–)-isochaetominine A was increased from 25.4% to 30.8% over five steps. Secondly, a new protocol featuring the use of an aged solution of K2CO3/MeOH to quench the DMDO epoxidation-triggered cascade reaction was developed, which allowed the in situ selective mono- or double epimerization at C11

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

• ) catalytic cycle [28]. However, in the case of Cu(OTf)2, the active catalytic species must be generated in situ. The highest diene 10a NMR yields (63–66%) were achieved by using 20 mol % of CuCl, 3.0 equiv of Ph2IOTf (I-2) and 1.2 equiv of 2,6-di-tert-butylpyridine (B1) in EtOAc at 70 °C (Table 1, entries 16

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

• ring was assembled via a one-pot mercuriocyclization/reductive demercuration of 153 followed by two-step diol-deprotection to access compound 154. Using trifluoromethylmethyldioxirane, which was generated in situ from trifluoroacetone, Oxone®, and disodium ethylenediaminetetraacetate dihydrate (Na2EDTA

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

• significant attention in this context due to its flexibility, efficiency, and practical applicability. Since the late 1980s, many research groups have investigated the use of in situ-generated low-valent titanium [20][21][22][23][24][25] and niobium [26] reagents to promote the pinacol-type coupling of imines

• described a new electrochemical procedure to provide vicinal diamines involving the use of Sn electrodes as both anode and cathode in a divided cell, Mn(OAc)3·2H2O as additive and n-Bu4NOAc as electrolyte. Under these conditions, using aldehydes and amines as starting materials to form the imines in situ

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

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• styrene, leading to the in situ generation of two valuable intermediates that act as dual synthons for the synthesis of 2,4- and 4-substituted quinolines. As part of our ongoing efforts to develop innovative C–C and C–H activation strategies for constructing nitrogen-containing heterocycles [55][56], we

• during GC–MS analysis) and formaldehyde (2a′′) via C–C bond scission of styrene in the presence of FeIII/O2, possibly through a 1,2-addition of O2 to styrene [49][58][59][60]. This in-situ generated aldehyde species then undergoes condensation with the amine 1a, leading to the formation of the

• cleavage of styrenes, catalyzed by earth-abundant iron, followed by the in-situ utilization of the resulting cleaved synthon in a domino process to synthesize highly substituted quinoline derivatives. We have demonstrated that this process can efficiently convert readily available feedstocks, including a