Rh(III)-catalyzed chelation-assisted C–H activation/annulation of 2-arylimidazolines with cyclic diazo-1,3-dicarbonyl compounds: a novel approach to tetracyclic annulated derivatives of 2,3-dihydroimidazo[2,1-a]isoquinoline

• Ivan Lyutin,
• Grigory Kantin,
• Olga Bakulina and
• Dmitry Dar'in

Beilstein J. Org. Chem. 2026, 22, 997–1003, doi:10.3762/bjoc.22.78

• immunosuppressive activity. The latter was used to develop antiasthmatic, pulmonary, and anti-allergy agents acting as platelet-activating factor receptor (PAF-R) antagonists [12][13]. Derivatives with X = H were accessed only via lithiation of 2-(o-tolyl)imidazolines followed by condensation with aromatic esters

• azides, while 2-arylimidazolines 2 were prepared via condensation of aromatic aldehydes with ethylenediamine in the presence of N-bromosuccinimide [25]. We began our investigation with the model reaction of 2-(4-chlorophenyl)imidazoline (2a) with 2-diazodimedone (3a), which resulted in the formation of

• protodemetallation that delivers CAr-alkylated intermediate F and regenerates the active catalytic species. The target tetraheterocyclic product 4 is formed after intramolecular condensation between the carbonyl group and the imidazoline nitrogen of intermediate F. To support this mechanism experimentally, we have

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• presence of CuI (3 mol %), affording the corresponding isoindolinone products 28 in good to excellent yields (79–92%). Mechanistically, the transformation involves a Cu(I)-promoted oxidative amidation followed by intramolecular aza-Michael cyclization. Initially, the condensation of amine with the aldehyde

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• Timur O. Zanakhov Ekaterina E. Galenko Mikhail S. Novikov Alexander F. Khlebnikov Saint Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya Naberezhnaya, St. Petersburg 199034, Russia 10.3762/bjoc.22.70 Abstract The Cs2CO3-induced condensation of 2-(diazoacetyl)-2H-azirines

• [4.1.0]heptan-5-one derivative. The acid-catalyzed transformation of which leads to 2-aroyl-3-hydroxy-1H-pyrroles. Keywords: azirines; condensation; cyclization; diazo compounds; pyrroles; Introduction Diazo compounds play a significant role in the synthesis of heterocyclic compounds, which explains

• . Considering that the condensation of acyldiazomethanes to aldehydes leads to the β-hydroxy-α-diazo carbonyl compound [20][21][22], we hypothesized that such condensation of aldehydes with 2-(diazoacetyl)-2H-azirines could yield the corresponding azirinyl-substituted diazo compounds. This paper describes the

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• cysteine [15]. These intermediates enable downstream chemical conjugations such as Pictet–Spengler condensation [16][17][18] and Horner–Wadsworth–Emmons (HWE) olefination [19] (Scheme 2c). With respect to C-terminal modification, one of the earliest strategies involved the use of intein-mediated protein

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• complexity and, in some cases, unexpected reaction outcomes. In reactions involving amino acids or diamines, the coexistence of multiple nucleophilic and electrophilic sites can give rise to competing pathways and polycyclic architectures. A well-documented example is the condensation of isatin (1) with ʟ

• may proceed beyond simple imine formation and generate highly condensed frameworks. A related behavior has been observed in reactions of isatin with diamines. Whereas condensation with propan-1,3-diamine (10) under controlled stoichiometry affords the corresponding diiminoisatin 11 (Scheme 2) [18

• aromatic pattern of the isatin core. The IR spectrum showed a strong imine C=N band at 1610 cm−1, and the absence of the C-3 carbonyl stretching band confirmed complete condensation. The 13C NMR spectrum revealed multiple sets of closely related signals, consistent with the presence of three C=N

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• . However, there are currently only limited methods for their synthesis, which are complicated and typically based on modifications of 4,5-diazafluorenone. Herein, we systematically studied the Knoevenagel condensation of both 4,5- and 1,8-diazafluorenes with aromatic aldehydes and evaluated the

• diazafluorenes’ nature and solvent influence on the mechanism and reactivity. We also identified conditions allowing the preparation of both 4,5- and 1,8-diazafluorenylidenes in yields up to 85% minimizing complicated synthetic or experimental workup procedures. Additionally, the condensation of diazafluorenes

• with ketones resulted in unique di(pyridin-2-yl)methylene)-9H-diazafluorenes being electron-deficient ligands and functional materials. Keywords: acidic conditions; diazafluorene; diazafluorenylidene; Knoevenagel condensation; protonation; Introduction Diazafluorenylidene derivatives were reported to

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• MASH. Results and Discussion Chemistry The synthetic routes to the target compounds are outlined in Schemes 4–8. The synthesis of isoxazole intermediate 2 commenced with the condensation of commercially available benzaldehyde I with hydroxylamine to afford oxime intermediate II. Subsequent treatment of

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• acid or its ester (Scheme 1). In both cases, condensation of amino acids with carbonyl compounds occurs; however, in the first case, decarboxylation occurs with the in situ formation of azomethine ylides, which subsequently undergo cycloaddition to unsaturated substrates. The advantage of the first

• iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl

• azomethine ylides Formation of azomethine ylides via decarboxylative condensation of amino acids and aldehydes Ronald Grigg and colleagues were the first to describe the generation of azomethine ylides by condensation and decarboxylation of primary or secondary α-amino acids with various aldehydes. Early

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• condensation of dimethylallyl pyrophosphate (DMAPP) with different numbers of isopentenyl pyrophosphate (IPP) [6]. Two naturally existing pathways, i.e., the methylerythritol phosphate (MEP) pathway and mevalonic acid (MVA) pathway, as well as artificially designed pathways, such as the isopentenol utilization

• and 3 was reported in 1988 starting from 3-vinyl-2-cyclohexen-1-one featuring a key intramolecular aldol condensation reaction [33]. On the other hand, semisyntheses of 2 were achieved starting from related terpene products, including elemol (featuring a Hg(OAc)2-mediated oxymetallation) [34], β

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• -hydroxyphenyl)calix[4]pyrrole, commonly referred to as phenoxycalix[4]pyrrole (PCP). It was first reported in 1999 by two independent research groups, Floriani et al. and Sessler et al., via the acid-catalyzed condensation of pyrrole with p-hydroxyacetophenone [17][18]. PCP and its derivatives were first known

• methanesulfonic acid as first reported by Floriani et al. [17] and Sessler et al. [18]. This condensation reaction produces several PCP isomers, including the targeted pre-organized α,α,α,α-isomer, which is isolated by crystallization from glacial acetic acid, followed by removal of the acetic acid using a

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• unrealized. This result places the cyclocondensation reaction that generates compound 968 within a family of three-component reactions of 1,3 dicarbonyl compounds, an aryl aldehyde, and various 1,3 di-nucleophiles (Figure 4). These reactions proceed by an aldol condensation between the dicarbonyl and

• aldehyde, followed by conjugate addition and cyclo-condensation with a 1,3 dinucleophile. Members of this reaction family are variations on the Biginelli and Hantzch reactions, where the dinucleophile is urea and the ammonia adduct of a second equivalent of the dicarbonyl, respectively [31]. A similar

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• undergo semi-pinacol rearrangement, resulting in the desired 1,2-alkyl shift to form the 5-membered ring in intermediate 134b. Alternatively, an isomerised compound with olefins in positions 7/8 and 14/15 instead of 6/7 and 8/14 could be oxidatively cleaved and undergo aldol condensation. In any case the

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• ylide, which is generated in situ by condensation of alloxan and ʟ-proline, can react with maleimides to give spirobarbiturate-pyrrolo[3,4-a]pyrrolizidine-1,3-diones in moderate to good yields. We have demonstrated the possibility of using a wide range of N-substituted maleimides as dipolarophiles. All

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• 1,4-addition. No condensation products were obtained and the reaction mixtures consisted solely of starting materials. It is likely that under these conditions, the nucleophilicity of 4-hydroxyquinolinones was insufficient to attack the aldehyde carbonyl, preventing product formation (Scheme 4F

• presumably proceed through in situ formation of the Michael acceptor from the condensation of an aromatic aldehyde with Meldrum’s acid, followed by decarboxylation and lactonization to yield the pyranoquinolinedione products (Scheme 1). We hypothesized that employing an alcohol as solvent could induce

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• elimination of H2O. Then, two MPP molecules undergo a dehydration condensation reaction to form DPpyP [56]. Finally, the phenoxy anion undergoes a nucleophilic attack on the phosphorus atom of DPpyP, and DPP is formed through the elimination of MPP. In the absence of triethylamine, the esterification reaction

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• complex methods of oxidation. Condensation using established methods would then allow the synthesis of compound 1 in four steps overall, as shown in Scheme 2 [8][18]. To begin this synthesis, we needed to selectively nitrate p-bromotoluene (5), ortho to the methyl group, to yield 3. Adapting the

• with yields ranging from 18 to 60.5% yield relative to starting 3 [8][9][11][12]. Chromium-free oxidation of 3 to 4 has been reported via the condensation of 3 with an alkyl nitrate to yield an oxime. Subsequent hydrolysis of the oxime yields the desired aldehyde 4, but only in low yield [6][7

• reaction pathway most consistent with our goals. Condensation of 4-bromo-2-nitrobenzaldehyde (4) to 6,6’-dibromoindigo (1) was accomplished via the Baeyer–Drewson process initially developed for the synthesis of indigo [8][18][24]. As shown in Scheme 6, treatment of 4 with sodium hydroxide in aqueous

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• . Heating these precursors under flash vacuum pyrolysis conditions at 230 °C led to the removal of the Boc group and intramolecular dehydration–condensation, thereby constructing the diketopiperazine core and enabling the total syntheses of ditryptophenaline (70), dibrevianamide F (71), and tetratryptomycin

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• metabolite. Historically, (3S)-3-indolylbenzodiazepine-2,5-dione ent-5 was isolated for the first time as a natural metabolite from the fungal culture extract of Aspergillus flavipes by Barrow and Sun [15] and synthesized by the condensation of isatoic anhydride and ʟ-tryptophan as previously reported by

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

• -1-yl)ethane-1,2-dione [57], or 4-(4-phenyl-2-(trifluoromethyl)oxazolidin-2-yl)butanoic acid under acidic conditions [58], and condensation of 6,6,6-trifluoro-5-oxohexanoic acid with (S)-(+)-phenylglycine [59]. The data on the multicomponent synthesis of fluoroalkyl-containing pyrido[1,2-a

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

• , vinylogous Mannich reaction of the in situ-generated aldimine condensation product of 49 and amine 50 with trimethylsiloxyfuran 51 generated secondary amine 52 in a diastereomeric ratio of 10:1. To close the piperidine, which is to become the F-ring, six steps were carried out: 1,4-reduction of the

• saturation, resulting in a spirocyclization, which we have seen in strategies toward cyclopamine before. As already stated, the synthesis commenced with the sequential construction of the ABCD-ring system in 25 steps to arrive at ketone 62 (Scheme 14). The F-ring was attached via condensation with piperidine

• the semisynthesis of Liu/Qin [26] 15 years later. The only non-green transformations displayed at the start were a protecting group installation (red) and a condensation (yellow), which was needed for the C–H activation (light green). All other transformations connect either C–C or C–heteroatom bonds

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

• condensation-type reaction using ethylenediamine (EDA) as catalyst in AcOH under microwave (μw) heating. This convenient methodology is broad in scope, provides the condensation products in high yields (up to 99%), with a reasonable catalyst loading (10 mol %) in only 30 minutes. This approach also enabled the

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

• cation were consistent with earlier reports [2][26], though the configurations of the intermediates were clearly delineated. The authors proposed that dicarbonyl compound 50 serves as the key intermediate diverging to all Illicium sesquiterpenes, with a retro-Dieckmann condensation and aldol reaction

• protected prior to the RCM step. Oxidative cleavage of the cyclopentene followed by Pinnick oxidation of the resulting aldehyde to the carboxylic acid and esterification yielded ketoester 56. Dieckmann condensation of 56, esterification of the resulting enolate with 57, and subsequent one-pot partial

• introduced a tertiary alcohol at the C4 position, yielding retro-Dieckmann precursor 61. Subsequent retro-Dieckmann condensation under basic conditions, deprotection of the PMP group, and selective ketalization of the C11 carbonyl group afforded compound 62. The C1 methyl group was installed via enol

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

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• cyclohexane/ene ring contraction. The structure of the review includes examples of simple transformations (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, and Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements (photochemical, benzil, semi-pinacol, Wolff, Meinwald, Wagner–Meerwein

• aldol condensation of the resulting dialdehyde. This strategy is widely used at the key stage in the formation of a cyclopentane ring in the synthesis of various building blocks, including echinopine A (3) [10][11][12] (Scheme 1). The ozonolysis–cyclization sequence was used by Alvarez-Manzaneda et al

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

• underwent ketone release and amine-ketone condensation to form iminium ion 27. Under the same acidic conditions, enamide 26 underwent hydrolysis and tautomerization to form enol 28. Conjugate addition of enol 28 to iminium ion 27 gave 29 for the subsequent intramolecular Mannich cyclization to deliver 30

• , which continued with an amide-ketone condensation to finally produce 31 in this highly efficient one-step biomimetic cascade sequence. The secondary amine of 31 was selectively protected as a Boc carbamate and the dihydropyridone moiety was oxidized to a pyridone with Pb(OAc)4. Pyridone 32 was prepared

• hemiaminal opening and amine–ketone condensation, iminium ion 65 was produced for the next pyrrole nucleophilic addition to form a strategically important C–C bond and afford 66, which was protected as Boc carbamate in the same pot to give 67 in 96% yield from 64. In this tandem sequence, the nucleophilicity