Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• virtually any functional units attached to them via triazole groups. Keywords: calixarene amines; dimeric capsules; functionalization; tetraureacalixarenes; triazoles; Introduction Considered generally as multifunctional molecular cores, calixarenes in their native forms as cyclic oligophenols actually

• groups, or vice versa. Of these two possibilities, the triazole synthesis conducted prior to the target acylation of amines seems to be more convenient, as the acylation may proceed under milder conditions than the CuAAC reaction. Even more important, the amine-derived functional units may interfere or

• affect the cycloaddition by, for instance, binding copper cations or counter anions, and thus their presence in the structures of calixarenes at the CuAAC step must be avoided. On the other hand, the unmodified amines may also contribute to undesired Cu(I) stabilization and complicate the CuAAC work up

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• of the quaternary ammonium salt in the presence of a O-, S- or N-nucleophile with cesium carbonate leads to a retro-Claisen reaction, ring-opening and Michael addition. The resulting novel 4-Nu-3-sulfonylbutan-1-amines are isolated in moderate to excellent overall yields. The reduction of the

• effects [14], сoagulation enzyme factor (FXa) inhibition [15] and antidepressant properties [16]. Considering the approaches to the synthesis of γ-aminosulfones, we focused our attention on the implementation of an aminoalkylation as a powerful and versatile tool for the synthesis of aliphatic amines [17

• -step method for the synthesis of N,N-dialkyl-3-(sulfonyl)butan-1-amines. Results and Discussion We began our survey with the examination of the pyrrolidination reaction [35][36] of β-ketosulfones (Scheme 1). This domino reaction of an active methylene compound, N-methylglycine and paraformaldehyde

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• nucleophilic anilines and bulky secondary amines also reacted smoothly, affording the corresponding amide products 104–107 in high to excellent yields. With respect to the R¹ substituent, phenyl, electron-rich phenyl, electron-poor phenyl, and heteroaryl groups were all well tolerated, affording the

• . Bioactive molecule-derived amides with complex structures smoothly underwent acyl iodide generation, thereby furnishing the products 132, 133, and 134 in 85%, 82%, and 88% yield, respectively, via in-situ amidation with aniline. The scope of amine nucleophiles was broad as well. Anilines, primary amines

• , and secondary amines all furnished the corresponding amides 135–143 in high yields, though the sterically hindered 1-adamantylamine afforded the corresponding amide 142 in a moderate 56% yield. Notably, the tertiary amide moiety was cleaved with excellent chemoselectivity even in the presence of other

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• nitroxides 2d–f, the samples of the radicals were reduced to the corresponding diamagnetic amines using a Zn/CF3COOH system in CD3OD at 63 °C, according to a literature protocol [23] and the 1H NMR spectra were recorded. The spectra showed similarity to those of previously described for radicals 2a–c [20

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• ], allylgrignards [78], amines [79], and allenylstannanes [80], thereby accessing the corresponding propargyl-functionalized products (Scheme 6B). In parallel, Bao and co-workers demonstrated that the dearomatization manifold extends beyond simple benzenoid systems to include heteroarenes such as furans, thiophenes

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

• , replacing alcohols with secondary amines (e.g., pyrrolidine) as the reaction medium did not lead to the desired amides. Experimental trials resulted in the formation of complex mixtures (as confirmed by 1H NMR), suggesting that the high reactivity of amines interferes with the selectivity of the cascade

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• partial positive charge on the i-positioned carbon atom [36], confirmed by an unusually downfield shifted signal of the CH fragment in the 13C NMR spectrum (δ 160.4 ppm in CD3CN) [21]. Moreover, anion 2 underwent a nucleophilic attack onto the i-position by amines to form fluorescent 5

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• acetylenic ethers [97][98], ynones [99], ynamides [98][99][100][101][102], acetylenic selenides [103], thioalkynes [98][104], acetylenic nitriles [105], propargyl amines [106], propargylic amides [107], propargylic thioethers [106], propynoic acids [105], and propynoates [105][108] (Figure 8). Over the past

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

• the mechanistic aspects of these transformations. Our team has discovered a new multicomponent synthesis that is based on autocatalyzed reactions of ethyl trifluoroacetoacetate and other polyfluoroalkyl-3-oxo esters with α-methylenecarbonyl compounds and amines [9]. This approach is appropriate only

• minor when heated in 1,4-dioxane (Scheme 3, Table 3). Previously, we proposed and experimentally confirmed an aldol mechanism underlying the three-component cyclization of polyfluoroalkyl-3-oxo esters with α-methylene ketones and amines in piperidone derivatives. According to this mechanism, the key

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• and X-ray diffraction. Synthesis of isothiazolium thiocyanates 2 and 4-thiocyanato-2,5-dihydrofuran-2-amines 3. Typical procedure. A solution of iminopropargyl alcohol 1 (0.5 mmol, 1 equiv) in 3 mL of acetonitrile was quickly added to a mixture of sodium thiocyanate (1 mmol, 2 equiv) and 1 mL of

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• substitution reactions of benzo-1,3-dioxoles and benzo-1,4-dioxanes [20]. Reduction of ketones 6 and 7 with NaBH4 gave alcohols 16 and 17, which were chlorinated with SOCl2 to result in compounds 18 and 19. Treatment of the latter with the appropriate amines gave amino derivatives 20a, 20c–e, and 21a, 21c–p

• ): reduction of 8 with NaBH4, followed by chlorination of alcohol 36 with SOCl2 and substitution of chloro derivative 37 with various amines resulted in compounds 38a–c. Tianeptine analogue 38d was obtained by hydrolysis of ester 38c. The synthesis of the new regioisomeric tetracyclic compounds containing the

• intermediates 40‒43 to chloro derivative 44, which was converted with amines to compounds 45 and with methanol to ether 46. Finally, we synthesized related tetracyclic derivatives containing the ethylenedioxy moiety attached to positions 2 and 3 of the dibenzo[c,f][1,2]thiazepine (1) core (Scheme 8). While the

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

• -benzylidenethiazol-4-one (3’) in moderate yield (Scheme 1). The implications and scope of this finding will be published in due course. Switching to aromatic (pyridine) or tertiary amines (Et3N) resulted in low yields (Table 1, entries 11 and 12). In contrast, the use of ethylenediamine (EDA) stood out, delivering

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

• –C, C–HA bond-forming reactions [36][37]. These chiral NHC catalysts, used to access enantiopure alcohol/amine derivatives, particularly 2° and 3° alcohols/amines, are significant structural motifs in numerous drugs and natural products and have found widespread synthetic applications in medicinal

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• where the attachment of alkyne and azide functional groups was reversed, as summarized in Table 2. The azide analogs 19–24 [25][28][31][43] used in this study were prepared from commercially available amines using the Sandmeyer reaction (Table S2, Supporting Information File 1). Reaction of each azide

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

• NiCl2/NaBH4 in methanol at room temperature, affording the corresponding amine 4 in 93% yield. To align with green chemistry principles, we employed a recently reported mechanochemical protocol by Ito and co-workers for the reduction of nitro compounds to amines [72]. Using this solvent-free method

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

• 30% and a selectivity of 70% at −100 °C (Scheme 21). 2.3 Wolff rearrangement The Wolff rearrangement is the transformation of α-diazoketones into acids or their derivatives through heating, catalysis, or UV irradiation in the presence of water, alcohols, ammonia, amines, etc. The Wolff rearrangement

• contraction is demonstrated by the example of converting organoborane intermediates into alcohols, amines, and E-alkenes (Scheme 32). 4 Meinwald rearrangements of epoxides The rearrangements of oxiranes annelated to cyclohexane occupy an important place in the synthesis of cyclopentanes due to the

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

• . The past three decades have seen enormous advances in the development of enantioselective radical reactions, particularly using organocatalysts. Some of the notable chiral organocatalysts imparting enantioselectivity include chiral secondary amines, chiral Brønsted acids, and chiral H-bonding

• ]. 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

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

• , whereas internal alkynes favored the 8-endo-dig pathway due to steric constraints and carbocation stability. This strategy facilitated efficient and selective synthesis of macrocyclic amines, with precise ring size control via substituent modulation. In 2021, Liu group reported a BiCl3-mediated

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

• secondary amines through the combined use of a m-quaterphenyl probe 1 and theoretical calculations. The probe 1 is covalently attached to chiral amines to form conjugates that exhibit exciton-coupled circular dichroism (ECCD) in the m-quaterphenyl chromophores. The calculated ratios of the P and M

• ]. However, its use in the analysis of chiral amines has been restricted, largely due to the complexity arising from their conformational flexibility [3]. Circular dichroism (CD) spectroscopy offers a highly sensitive technique for stereochemical analysis at the microgram scale [4][5][6]. In particular

• for determining the absolute configurations of chiral alcohols [8][9][10][11][12][13][14], primary amines [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], secondary amines [33][34][35], carboxylic acids [36][37][38], sulfoxides [39], and cyanohydrins [40]. We have reported

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

• the synthesis of triazole-fused and tetrazole-tethered benzodiazepine 7a, we synthesized additional analogs by conducting the reaction of 2-azidobenzaldehyde (1a) with ten different isocyanides 3, two 2-yn-1-amines (propargylamine (2a), 3-phenylprop-2-yn-1-amine (2b)), and TMSN3 to give products 7a–k

• % isolated yield (Scheme 5). Next, the reaction scope was explored by reacting four different 2-azidobenzaldehydes 1 and five different 2-yn-1-amines 2 with 2-isocyanoacetate (9) and TMSN3 (4) to give products 8a–h (Scheme 6). The reaction of five different 2-yn-1-amines 2 yielded products 8a–e in 77–92

• % yields, which demonstrates a good tolerance of substituents R2 on 2-yn-1-amines 2. The reaction of 6-azidobenzo[d][1,3]dioxol-5-carbaldehyde (1b) with propargylamine (2a), 2-isocyanoacetate (9), and TMSN3 (4) gave product 8f in 77% yield. Azidobenzaldehyde bearing a Cl group gave product 8g in 79% yield

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

• alkynes, amines and azides, respectively. Imidazopyridines could be obtained by electrochemical [3 + 2] cyclization of heteroarylamines. The electrochemical oxidative [3 + 2] cycloaddition of secondary propargyl alcohols was a simple and efficient access towards 1,2,3-triazoles. In this review

• electricity as a sustainable and green oxidant, noble metal catalyst (Rh) was required to achieve reasonable yields. An electrochemical synthesis of imidazoles through tandem Michael addition/azidation/intramolecular cyclization of alkynes, amines and azides was realized by Chen in 2022 (Scheme 17) [267

• rt for 9 h. The reaction was compatible with numerous amines such as substituted benzylamines 46b–d, 1-(2-naphthyl)methanamine 46e, 3,4-methylenedioxybenzylamine 46f, furfurylamine 46g and 2-thiophenemethylamine 46h. Alkynes with ester and trifluoromethyl groups worked well under this reaction

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

• synthesis of amines by replacing the current toxic pathway based on ethylene oxide and dichloroethane [29]. Due to the high reactivity of α-hydroxycarbonyls, the main issue in this reductive amination reaction [30] was to control the cascade of consecutive and parallel reactions. The use of methanol as

• a C1 building block for the N-formylation of secondary amines to formamides under catalyst-free conditions and air as oxidant. This method was applied to different aromatic and aliphatic (both cyclic and acyclic) amines (Scheme 3) [31]. Already in 1955, Parham and Reiff reported the synthesis and

• single ion catalyst, Brückner and Shi synthesized value added formamides by treating amines with different C2 and C3 platform molecules like GA, glyceraldehyde (GLAD), and 1,3- dihydroxyacetone (DHA) (Scheme 9) [37]. C3 biobased carbonyl platforms Lactic acid (LA) Propanoic (or propionic) acid (PA), a

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

• position 12 [23]. The most straightforward synthetic strategy for formation of an carboxamide group at position 12 of the indolo[1,2-c]quinazolin-6(5H)-one (1) scaffold involved a two-step sequence: (1) carboxylation of the nucleophilic C12 position, followed by coupling with appropriate amines. To

• substitution of the terminal chloride in 11 with various cyclic amines, including pyrrolidine, piperidine, and mono-tert-butoxycarbonyl (Boc)-protected piperazine, provided a set of aminoalkyl derivatives 12а–с (Scheme 4). This strategy enables the expansion of structural diversity within this scaffold and

• ]quinazoline (13) was of particular interest, as the presence of a reactive chloromethyl group facilitates nucleophilic substitution with various amines. The compound 13 was synthesized according to a procedure described in the literature [28]. Subsequent displacement of the chloride in 13 with amines provided

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

• for the preparation of benzodiazepinone derivatives, which showed promising psychotropic effects [20][21][22][23][24], using a tandem combination of Ugi/azide–alkyne cycloaddition reactions. From this point of view, azido amines are promising reagents for use in the Ugi reaction, opening up the

• possibility of synthesizing various heterocyclic systems such as quinazolines [25], diazepinones [25][26], quinoxalinones [27], diazocinones [28], and imidazolines [29] due to the exceptional reactivity of the azido group. However, the use of azido amines in the Ugi reaction together with oxoacids, which have

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

• successful execution of this approach and the demonstration of biological function of the resulting reactive probes. Results and Discussion We prepared five α-diazoamide substrates bearing S(VI) electrophiles (Scheme 1 and Table 1) [15]. Initially, three amines – morpholine, 4-phenylpiperidine and