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

• ]. Some rhodanine-based derivatives act as inhibitors of hepatitis C virus (HCV) protease [19], UDP-N-acetylmuramate/ʟ-alanine ligase [20], histidine decarboxylase [21], aldose/aldehyde reductase [22], fungal protein mannosyl transferase 1 (PMT1) [23], metallo β-lactamase [24], cathepsin D [25], JNK

• aldehyde 1, activated by protonation of the oxygen atom through structure ii, forming the intermediate aldol iii. In the presence of EDDA, water elimination occurs in intermediate iv, yielding the Knoevenagel adducts 3 or 4. Synthesis of novel imidazo[1,2-a]pyridine–thiazolidinone hybrids To further

• , hybrid compounds combining the imidazo[1,2-a]pyridine scaffold with the thiazolidine nucleus were synthesized. Initially, aldehyde derivatives of the GBB adducts 8 were prepared from 2-aminopyridines 5, terephthalaldehyde (6), and isocyanides 7 using a green methodology that employed phosphotungstic acid

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

• 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

• enantioenriched compound 33, a nickel-catalyzed hydrocyanation of the terminal alkyne was performed. Subsequent protection of the tertiary alcohol with TESOTf and reduction of the resulting cyanide to an aldehyde afforded compound 34 (Scheme 4). Addition of isopropenyllithium to aldehyde 34, followed by TES

• deprotection, afforded enal 42. To avoid the chemoselectivity issues in the subsequent allylic oxidation and radical cyclization steps, enal 42 was converted to 43 by reduction of the aldehyde and protection of the resultant diol with Ph2SiCl2. Allylic oxidation of 43 with 44 [37] afforded the enone in 22

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

• , smoothly constructing the A ring to afford compound 14. Subsequent protection of the vicinal diol and aldehyde functionalities in 14 provides an intermediate that, after Baeyer–Villiger oxidation and subsequent tungsten-promoted reverse epoxidation, forms lactone 15. Ozonolysis of 15 cleaves the double

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

• smoothly to deliver the aldehyde which was immediately subjected to the condensation reaction with benzylhydroxylamine. The corresponding nitrone 10 then underwent an intramolecular cycloaddition. Adduct 11 was isolated as the major product in 42% yield for 2 steps. Comprehensive NMR analysis revealed the

• from the use of crotyl bromide as a mixture of geometric isomers. After installation of the crotyl group, hydrolysis of the acetonide group and oxidative cleavage of diol 16, oxime 17 was prepared through the condensation of the aldehyde with hydroxylamine in overall 59% yield. Upon oxidation with

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

• in a stable aldehyde 23. This aldehyde is a product of intramolecular aldol–croton condensation and can be used in the synthesis of bartsioside (24) or its analogues [21][22] (Scheme 4). The authors [19] performed similar oxidative transformations with Diels–Alder adduct 25 obtained from LG and

• 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

• allylic oxidation using H2SeO3-dioxane system to form the C30 aldehyde 47, or by the ozonolytic cleavage of the double bond between C20 and C29 to produce 20-methyl-3-ethyldiketone 48 [36]. Intramolecular nitrile–anionic cyclization of ketone 46 or diketone 48 under conditions of basic catalysis proceeded

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

• . This intermediate was intended to be prepared through allylation [36] with its precursor 15 accessible from aldehyde 16 and acetyl chloride through ketene–aldehyde [2 + 2] cycloaddition [37]. Results and Discussion Our synthetic route commenced from the known aldehyde 16 which is readily accessed in a

• single step from commercially available fructone [38] (Scheme 3). Following an efficient O-trimethylsilylquinine-catalyzed ketene–aldehyde cycloaddition and subsequent alkylation [36], 17 was synthesized. From 17, it was envisioned that the bicyclic skeleton could be efficiently constructed through ketal

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

• -chloroperoxybenzoic acid) induced epoxidation, which was then followed by a Meinwald rearrangement to accomplish aldehyde 7. From 7, a sequence involving silyl enol ether formation, Simmons−Smith cyclopropanation, and acid-mediated regioselective ring-opening installed the C8 quaternary methyl group in 10. Subsequent

• intramolecular aldehyde α-alkylation using MacMillan's protocol, subsequently undergoing Shi's asymmetric epoxidation to give rise to epoxide 60 as a 3:1 mixture of diastereomers. These were not separated until step 8 due to poor separability at this stage. Concurrently, diosgenin was then processed through a

• known two-step sequence to 61, followed by Mitsunobu reaction, ester reduction, thioether oxidation, and silylation of the primary alcohol to furnish sulfone 64. The two key fragments – aldehyde 60 and sulfone 64 – were merged via Julia–Kocienski olefination to construct alkene 65. Treatment of 65 with

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

• 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

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

• applied in the development of enantioselective polyene cyclizations, which demonstrated the power of the catalytic strategy. In the presence of a chiral amine catalyst 16 (Scheme 3) and the mild oxidant Cu(OTf)2, polyenes with a terminal aldehyde group underwent intramolecular cyclizations affording

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

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

• with linear alcohols using Cu2O–LiOH catalytic system or under oxygen, thus achieving a carbon-chain increase from C5 to C7–11 with potential applications in the field of liquid fuels. The conversion of furfural is up to 99.9%, while the selectivity of the corresponding aldehyde is up to 96.9%. The

• , arising from a nucleophilic attack of a furan carbon atom of one furfural molecule onto the aldehyde of a second one, giving 2-(4-furfur-2-al)-4-hydroxy-2-cyloepenten-1-one (Scheme 64), resulting from a Piancatelli rearrangement. This latter can further evolve towards more complex humin precursors by

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

• and aldehyde 37, which was prepared with 9 steps from commercially available (+)-citronellol, underwent a Reformatsky-type radical addition under the conditions of Et3B/air/Bu3SnH to deliver aldol product [16]. Dehydration of the secondary alcohol gave (E)-38. The HAT radical cyclization [17] of 38 in

• , 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

• transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• between an aldehyde, an amine, a carboxylic acid, and an isonitrile in 1959 [8], which marked the beginning of modern MCR chemistry, continues to attract undiminished attention. It has since been applied in manifold ways, from breathtaking reaction sequences and post-Ugi transformations to the generation

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

• introduce the carboxylic acid group a sequence of formylation/oxidation reactions was used. Vilsmeier–Haack reaction of 1 afforded 6-oxoindolo[1,2-c]quinazoline-12-carbaldehyde (2) (Scheme 1). All attempts to oxidize the aldehyde group of 2 to the corresponding carboxylic acid were hampered by the oxidative

• interest, compound 2 applied as a useful substrate for a Baeyer–Villiger oxidation mediated by oxone, which selectively converted the aldehyde to the formate ester, yielding 6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl formate (4). Subsequent hydrolysis of 4 furnished indolo[1,2-c]quinazoline-6,12-dione

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

• aldehyde 3. This linear aldehyde would be activated by an acid to trigger a key Prins cyclization with the trisubstituted olefin through reaction model 3 and generate a putative tertiary carbocation to be trapped by the chiral alcohol, providing bicycle 4 stereoselectively. Finally, the last olefin would

• 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

• TBS protection in one pot. Oxidation of the primary alcohol using Swern oxidation gave the hydroxy aldehyde 3, which was activated with a formal silicon cation to trigger the Prins cyclization terminated by the tertiary alcohol, affording silylated bicycle 9 directly through the designed bioinspired

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

• case of aldehyde 2b, the MCR always led to the formation of a mixture of products 5d and 6d. Attempts to synthesize 5d and 6d as individual compounds under various conditions were unsuccessful. In addition, it was found that compounds 5 can be converted into oxygen-bridged heterocycles 4 after 1 hour

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

• additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product. Keywords: carbenes

• transformations of carbonyl substrates with umpolung processes of aldehydes such as the benzoin condensation and Stetter reaction being particularly well studied [4][5][6][7][8][9][10][11]. In these processes, addition of the NHC to the aldehyde followed by proton transfer generates the enamine-like Breslow

• yield (Scheme 3c). The successful generation of the aldehyde from the azolium species derived from the corresponding carboxylic acid highlights the potential of this two-step sequence as a method for the partial reduction of carboxyl compounds. Such transformations can be challenging in organic

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

• 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

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

• Lewis acid-mediated semi-pinacol rearrangement, this work involved a CRL-catalyzed desymmetrization of prochiral diol 51 (prepared from aldehyde 50 in four steps), providing monoester 53 in 57% yield with 83% ee. Notably, 1-ethoxyvinyl 2-furoate (52) was selected as the acyl donor in this step to

• the cyclohexanone ring into 120, and the resulting hydroxy group was protected to give ketone 121. The γ-lactam moiety of compound 122 was then constructed in subsequent 12 steps. SmI2-mediated intermolecular Reformatsky-type reaction with aldehyde 123 yielded compound 124. Finally, salinosporamide A

• ) and the following acid-mediated cyclization formed another tetrahydrofuran ring. The resulting compound was then converted into lactone 174 via 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-mediated oxidation. Lactone 174 was then converted into aldehyde 175 in three steps, which underwent Horner

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

• 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

• the presence of a Lewis acid. The use of BF3·OEt2 gave a low yield of the desired alcohol 2 [29]. This was improved slightly with Sc(OTf)3 as the Lewis acid, which could be used substoichiometrically [30]. The alcohol 2 was converted to the tosylate 3 and subsequent ozonolysis gave the aldehyde 4. The

• aldehyde 4 could now be tested in the cascade chemistry. This entails the addition of hydroxylamine to form the oxime, followed by cyclisation (with displacement of the tosylate) to give the nitrone for the desired dipolar cycloaddition reaction. Related chemistry (without the oxindole) with a halide

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

• directly used as a planarly chiral primary amine catalyst in the asymmetric electrophilic amination reaction of aldehyde 34, which yielded the α-amination product 35 with high enantioselectivity. In 2022, our group disclosed an enantioselective macrocyclization protocol for the asymmetric synthesis of

• organocatalyst in the asymmetric amination of aldehyde 34, whereas inherently chiral aniline N-oxide 59 showed promise in the chiral recognition of mandelic acid. In 2024, Tong, Wang and co-workers disclosed an efficient method for synthesizing inherently chiral heterocalix[4]arenes through an asymmetric

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

• -triazoles 28 can be obtained by click chemistry (Scheme 6B) via one-pot deprotection of 26 and Cu(I)-catalysed reaction with an azide [43][44]. Heteroarylimines 31a,b can be easily obtained by condensation of a (hetero)aromatic aldehyde 30a,b with a (hetero)aromatic amine 29a,b [36][37][38] (Scheme 7). The

• choice of aldehyde and amine will determine the direction of the imine bond and the geometry of the Z-isomer. Examples Non-ionic bithienylpyrrole push–pull azo dye 32 was successfully introduced in liquid-crystalline matrices with thermal relaxation in the µs order, making them among the fastest liquid

• aldehyde and, if required, N-functionalisation via nucleophilic substitution (for aliphatic substituents) or palladium-catalysed cross-coupling (for aromatic substituents) (Scheme 25) [77]. Hemithioindigo can be synthesised by treating phenylthioacetic acid (83) with triflic acid. Then, the product is

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

• 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

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

• protonation of an aldehyde (Step_2’). Due to the higher basicity of the secondary amine compared with the carbonyl group of benzaldehyde, protonation of dimethylamine was the main reaction pathway (30.9 vs −2.6 kcal/mol). However, it was found that the protonation of the carbonyl group led to a great

• absence of an external hydrogen source. The alternative pathway to form a hemiaminal could not include the interaction of an acid with amine or aldehyde, nevertheless, the non-catalytic path had ΔEa = 32.1 kcal/mol (TS2→3'') which meant that hemiaminal definitely emerged faster via the amine protonation

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• condensation between 27 and the aldehyde afforded INT-A, which was activated by the CPA catalyst through hydrogen bonding interaction. The nucleophilic addition of isocyanide to Int-A produced INT-B bearing a stereogenic center. Subsequently, INT-B underwent intramolecular cyclization to generate axially

• bearing both C–C axial and central chirality (Scheme 9c) [57]. Key to this work relies on the implementation of an efficient Ag2O/L7-catalyzed desymmetric [3 + 2] cycloaddition of prochiral biaryl dialdehydes 62 with α-substituted α-acidic isocyanides. We have also demonstrated that the retained aldehyde

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• group in compound 10. Compound 10 can be realized by introducing an ester group in 9, which is the [3 + 2 + 1] cycloadduct from 8 and CO using a Rh catalyst. The [3 + 2 + 1] substrate of yne-vinylcyclopropane (yne-VCP) 8 can be synthesized by Wittig reaction from cyclopropyl aldehyde 7, in which the

• carbonyl group, giving 7 in 59% yield. Then, under basic conditions, the aldehyde group in 7 was converted into a vinyl group via Wittig reaction, affording yne-VCP substrate 8 in 90% yield. During this process, the TMS protecting group was lost. We then investigated the [3 + 2 + 1] reaction of 8 and CO