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

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• condensation-type reaction between aromatic aldehydes with rhodanine or thiazolidine-2,4-dione [39]. Various protocols have been reported employing diverse catalyst systems and reaction conditions. Common catalysts include inorganic bases such as sodium acetate (NaOAc) [40], urea/thiourea [41], NaOH [42

• applied to a variety of aromatic aldehydes (Scheme 2). Aldehydes containing halides (–F, –Cl, –Br) or strong electron-withdrawing groups at the ortho-position provided excellent yields (87–99%) for the 5-benzylidene-2-thioxothiazolidin-4-one derivatives 3b–e. The presence of an electron-donating group in

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

• carbenes (NHCs) with photocatalysts. The review encompasses transition-metal-based photocatalytic reactions for C–C and C–HA cross-coupling reactions involving various acyl fluorides, amides, aldehydes, carboxylic acids, and esters, highlighting their broad applications in organic synthesis and medicinal

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• , generating an N-centered radical species C. This species subsequently undergoes a rapid C–N cross-coupling with ketyl radical B. This cross-coupling method offers a transition-metal free route to highly substituted amides 3 from aldehydes 1 and imines 2, without the need for any external reductants or

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

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

• synthesis of natural products but also establish a solid foundation for subsequent pharmaceutical investigations. Keywords: dicarbonyls; natural product; Norrish–Yang cyclization; photoredox; total synthesis; Introduction In the 1930s, Norrish documented the photodecomposition of aldehydes and ketones [1

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

• low, the synthesis of 7c via this method represents a substantial improvement on previous approaches to this material [24]. The Baeyer–Villiger oxidation of 7c was uneventful and the fluorinated alkene 17 was isolated in 50% yield. The α-trifluoromethylation of ketones and aldehydes can be performed

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

• ]. MacMillan obtained chiral free radicals by stoichiometric single electron transfer (SET) oxidation of enamines, formed by the reaction between chiral secondary amines and aldehydes. This mode of activation was called SOMO (singly occupied molecular orbital) catalysis and was employed in several organic

• 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

• enantioselectivity. New catalytic methods have been developed by merging photoenzymatic catalysis with small-molecule photoredox catalysis. Enantioselective radical acylation reactions of N-hydroxyphthalimide esters and aldehydes, yielding α-substituted ketones, were catalyzed by a radical acyl transferase (an

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

• : aldehydes; biobased chemistry; biomass; carbonyl; fine chemicals; ketones; multicomponent; platforms; sustainability; Introduction Shifting towards sustainable practices in the chemical industry relies on continued advancement of green chemistry sciences which aim to minimize the global environmental

• -hydroxypropan-2-one and KSCN in ethanol for further evaluation of their anti-cancerous activity by MTT assays (Scheme 24) [99]. Notz and List reported the synthesis of anti-diols in good yield from 1-hydroxypropan-2-one and different (aromatic and aliphatic) substituted aldehydes using a new strategy using ʟ

• toward useful biobased functional compounds or intermediates with applications in fuels, polymer chemistry and fine organic synthesis (CH activation, Piancatelli rearrangement, etc.). Conversion of furfural to alcohols, aldehydes and ketones: One of the most important transformations of furfural is its

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

• concept of multicomponent-switched reactions [6] allows to tune the selectivity of MCRs and direct them into several different pathways. That is why the study of multicomponent heterocyclizations of aromatic aldehydes, compounds with an active methylene group and aminoazoles, for example with 3-amino

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

• library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of

• biochemical processes [47]. However, there are only a few studies in the literature on multicomponent reactions based on KGA. In 1992, Gein et al. [48] reported a multicomponent reaction involving KGA, aromatic aldehydes, and aromatic amines. This led to the formation of pyrrolone derivatives I, which showed

• anti-inflammatory activity [49][50] (Scheme 1, pathway A). In an earlier study by our research group, Sakhno et al. [51] described a three-component Doebner-type reaction involving KGA, aromatic aldehydes, and 3-amino-5-methylisoxazole, which led to the formation of [2-aryl-4-hydroxy-1-(5

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

• 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

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

• diimines of aromatic aldehydes with trans-1,2-diaminocyclohexane for the synthesis of enantiopure tetrasubstituted piperazines has been investigated by an electrochemical approach. The methodology was successfully developed under both batch and continuous flow conditions, and afforded enantiomerically pure

• 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

• chiral diimines of aromatic aldehydes with trans-1,2-diaminocyclohexane was initially investigated under traditional batch conditions through a series of screening experiments designed to find the optimal reaction conditions. Diimine 1a was selected as model substrate for the intramolecular coupling

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

• aromatization process, in 2023 our group reported the asymmetric synthesis of various azahelicenes 8 from polycyclic arylamines 5, dienamides 6 and aldehydes 7 (Scheme 2) [13]. This methodology demonstrates a broad substrate scope, enabling the efficient asymmetric synthesis of diverse aza[5]helicenes 8a–d and

• aza[4]helicene 8e from various aldehydes with high enantioselectivity. In addition, dienamides were found to be compatible with this method, albeit requiring a switch to CPA 3 as the optimal catalyst, which generated the 1-enamide-substituted azahelicenes 8f,g, with significant potential for diverse

• reaction with polycyclic arylamines 9 and various aromatic aldehydes 11, resulting in a range of quinoline-containing azahelicenes 12 with moderate yield and excellent enantioselectivity after DDQ-mediated oxidative aromatization (Scheme 3). Notably, they not only expanded the substrate scope to encompass

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

• of carbonyl compounds, such as aldehydes or ketones, with active methylene compounds [37]. The resulting α,β-unsaturated carbonyl products can then be further elaborated to form natural products, therapeutic agents, polymers, pesticides, and insecticides [38], which have important applications in the

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

• condensed with a (hetero)aromatic aldehyde in the presence of a base to yield 86 (Scheme 26) [81]. Iminothioindoxyl can be synthesised in the same way, using nitrosoarenes instead of aldehydes [90]. For several other synthetic methods, we refer to the excellent reviews by Konieczny and Konieczny [92] and

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

• -metal catalysts. One of the key transformations in organic synthesis is the selective oxidative cleavage of alkenes to yield ketones or aldehydes [43][44][45][46][47]. Traditionally, such transformations have been achieved using various oxidizing agents, transition-metal-based systems, organo- and

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

• experiments were carried out. During the substrate screening we noted that reaction between aldehydes and primary amines resulted in only traces of the product of reductive amination. In these reaction mixtures, exclusively Schiff bases were detected since they precipitated under neat conditions and left the

• efficiency falls down for some products, in particular, those containing electron-withdrawing groups. Wide range of amines was synthesized in moderate to good yields. Aliphatic ketones, aliphatic and aromatic aldehydes have successfully reacted with primary and secondary amines. Multiple bonds

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

• ] involving 6-aryl-2-aminopyridines 27, aldehydes, and isocyanides (Scheme 5a) [35]. By employing chiral phosphoric acid (CPA) C1 as the catalyst, this reaction worked well to afford axially chiral imidazo[1,2-a]pyridines 28 in high-to-excellent yields (up to 99%) and enantioselectivities (up to >99% ee). It

• distortion of isocyanoacetate–Ag coordination combing with better Ag–C σ-orbital overlap led to exo-cycloadducts (L10-TS). Except for constructing C–N and N–N axial chirality, we have developed a highly diastereo- and enantioselective method to access tri- and tetra-ortho-substituted biaryl aldehydes 63

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• on our earlier publications and the data presented here, it is reasonable to predict that the high-pressure activation strategy will gain broad application possibilities in the future. Experimental Materials and methods Materials: All substrates (aldehydes, hydrazones, alcohols, p-aminophenol

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• base [5]. In fact, its hydrogen-bond-accepting ability is even stronger than that of the other 3-, 5- and 6-membered cyclic ethers, as well as the carbonyls of aldehydes, ketones, esters and carbonates [6][7][8]. The only better carbonyl-based hydrogen-bond acceptors are amides, carbamates and ureas [9

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• -like electronic structure. Liu and co-workers developed a modular approach to for synthesizing azulene-embedded isomers of linear acenes (Scheme 11) [59]. Precursors 67–70 were obtained from aldehydes and substituted cyclopentadienes using Knoevenagel-type condensation. Finally, intramolecular

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• moieties of biologically active compounds. A salen–scandium triflate complex-catalyzed asymmetric (3 + 2) annulation of dialkyl 1-sulfonylaziridine-2,2-dicarboxylates and aldehydes generated optically active functionalized oxazolidine derivatives in moderate to good yields and good to excellent

• alcohols and aldehydes [11] and through [2 + 3] cycloaddition of azomethine ylides and carbonyl dipolarophiles [12]. Recently, the [2 + 3] annulation of aldehydes and donor–acceptor dialkyl 2-aryl-1-sulfonylaziridine-2,2-dicarboxylates, which generate azomethine ylides, has been developed for the synthesis

• -dicarboxylates from aldehydes and dialkyl 2-aryl-1-sulfonylaziridine-2,2-dicarboxylates under the catalysis of the readily available salen–Sc(OTf)3 complex (Scheme 1d). The salen ligand can be prepared in one step from enantiopure cyclohexane-1,2-diamines and substituted salicylaldehydes. Results and Discussion

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• advancements in this area have recently been demonstrated to access conjugated alkenes, particularly cinnamic acid derivatives, with high stereoselectivity. For instance, Reeves and co-workers (2023) performed a Horner–Wadsworth–Emmons reaction of triethyl 2-fluoro-2-phosphonoacetate (390) and aldehydes to

• , Maulide and co-workers (2022) utilized a novel thiouronium ylide 396 and 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (395) for the olefination of aldehydes to generate the corresponding cinnamates 398 and 399 with excellent (Z)-selectivity (Scheme 85). Interestingly, exchanging aldehydes for tosylimines

• catalytic Wittig reaction using phosphetane oxide 412 as redox cycling catalyst using silanes as the reductant to convert aldehydes and α-bromoesters into the corresponding cinnamate esters 44, 154, and 413. The reaction proceeds via formation of nucleophilic phosphane 414 (Scheme 87A) [147]. Moreover

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• are important intermediates in organic syntheses because of the versatility of the cyano group, which can be readily transformed into a wide range of functional groups, including amides, carboxylic acids, amines, aldehydes, ketones, and N-heterocycles [6][7][8]. However, the synthesis of all-carbon