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

• constructing the structure of spiro[indoline-3,2'-pyrrole]. In a study by Zhao and co-workers, asymmetric 1,3-dipolar cycloaddition of azomethine ylides derived from isatin and benzylamines to maleimides was catalyzed by Cinchona alkaloid-based squaramide L24 (Scheme 49) [99]. The cycloaddition proceeded

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

• extractants. Here, we report the design and synthesis of PCP HA, a phenoxycalix[4]pyrrole scaffold functionalized with four hydroxamic acid (HA) groups, and evaluate its uranium(VI) extraction potential. PCP HA was synthesized from its ester precursor (PCP E) via hydroxyaminolysis using KOH, achieving a 95

• supramolecular material for the removal of uranyl from aqueous media. Keywords: gamma spectroscopy; hydroxamic acid; phenoxycalix[4]pyrrole; solid–liquid extraction; uranyl(VI) extraction; Introduction Over the past few decades, supramolecular chemistry has advanced intensively establishing itself as a central

• their 2,5-positions through sp3-hybridized meso-carbon atoms [10]. The ability of CPs to selectively bind anions [11], cations, ion pairs and neutral guest species, combined with the versatility to introduce diverse functional groups, has enabled the fabrication of calix[4]pyrrole-based supramolecular

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• attributed to magnetic coupling between the face-to-face terminal rings, in line with the Johnson–Bovey model, given the inter-ring distances of approximately 3.75–3.79 Å [59]. On the other hand, the aromaticity of the pyrrole rings (A and A′) and benzene rings G and G′ in 5a and 5b decreases, which can be

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

• its utility. For example, while Os(II) displays a marked preference for coordination at the C(2) and C(3) positions of pyrrole, it can also access the less stable 3,4-η2-isomer (Figure 7C) [51]. This species exhibits significantly higher reactivity in certain transformations. In this way, η2

• -coordination of pyrrole transforms the aromatic framework into an azomethine ylide intermediate. This reactive species can engage in a [3 + 2] cycloaddition with activated olefins such as maleic anhydride to form 7-azabicycloheptene complex 8 rather than an electrophilic addition product. An analogous scenario

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• example, an amphiphilic poly(methyl methacrylate)-based polymer modified with calix[4]pyrrole was found to form micelles in water that capture anions from caesium salts and can be precipitated from solution upon heating [11]. Similarly, a hydrogel composed of poly(vinyl alcohol) cross-linked by a “Texas

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

• activities and serves as a potent modulator of intracellular calcium release channels. In contrast to ryanodol (4), compound 1 possesses a pyrrole-2-carboxylate ester moiety at the C3 position. This ester group can be cleaved via hydrolysis to yield 4. However, the reverse transformation – the synthesis of

• ryanodine (1) from ryanodol (4) – had long eluded chemists. The primary challenge involved the selective installation of the bulky pyrrole unit onto the sterically congested C3 secondary hydroxy group within a polyfunctionalized, polyhydroxylated framework. In 2016, building upon prior work, the Inoue group

• 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

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative

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

• a novel single-atom skeletal editing strategy [32][33] to form the pyridine from a pyrrole and a similar pyridine N-oxide directed ortho C–H arylation to forge the C2–C3’ linkage as the Tsukano synthesis, but with a much less reactive 3-chloropyridine as the cross-coupling partner. As shown in

• Paal–Knorr pyrrole synthesis delivered 63, which was unstable and spontaneously cyclized to provide 64. Compound 64 was then advanced to tetracyclic intermediate 67 in a one-pot tandem process, which initiated with Staudinger azide reduction with PPh3 to form a primary amine. After reversible

• 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

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

• that β-cyclodextrin (Figure 1)-based polymers could remove organic micropollutants from water [15][16]. For example, in 2021, Sessler and co-workers reported the synthesis of a calix[4]pyrrole (Figure 1)-based porous organic polymer, which exhibits the rapid uptake of dyes from water [17]. In addition

• uptake capacity of H2 for methylene blue, it must be substantially lower than that of previously reported pillar[5]arene (51 mg g−1) and calix[4]pyrrole (454 mg g−1) polymers [17][20]. Host G2W1 functions the best as sequestrant for methylene violet achieving an 87% removal efficiency when excess G2W1

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

• -dioxides, we aimed at elaborating a synthetic procedure for the preparation of their pyrrole-fused counterparts, 2,9-dihydro[1,2,3]thiadiazino[5,6-g]indole 1,1-dioxide derivatives. The simple and versatile process led, via Fischer indole cyclization of the corresponding hydrazones, to a wide structural

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

• nucleophilic substitution of D afforded target indeno[1,2-c]pyrrole 40a along with eliminating I. Notably, this oxidant-free and catalyst-free approach could be potentially applied in the pharmaceutical manufacture. A Rh-promoted synthesis of pyrroles through annulation of alkynes and enamides was demonstrated

• by Ackermann in 2023 (Scheme 16) [266]. Using GF as anode, Pt as cathode, NaOAc as the electrolyte and [Cp*Rh(MeCN)3](SbF6)2 as the catalyst, the annulation between alkyne 41 and enamide 42 succeeded, forming the corresponding pyrrole 43 in good yield. Although this transformation employing

• and reductive cascade annulation of o-alkynylbenzamides. An electrochemical intramolecular 1,2-amino oxygenation of alkynes provided indolizines in reasonable yields. The electrochemical multicomponent reaction was also developed for the construction of oxazole. Pyrrole could be prepared by

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

• [188]. Conversion of furfural to pyrrole and proline: Zhou and Yan reported a route bridging commercial biomass feedstock with high-value N-containing chemicals through pyrrole as a hub molecule. Furfural was converted into pyrrole in 75% yield via tandem decarbonylation–amination reactions over tailor

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

• wavelength (P-type) or through thermal back isomerisation (T-type). As a general rule, the absorption can be red-shifted by the choice of electron-donating rings (pyrrole, thiophene), while electron-withdrawing rings (pyridine, pyrimidine, pyrazole, imidazole, thiazole) give the opposite effect [12

• photophysical properties of this photoswitch class. The vast possibility of combinations and the straightforward syntheses make these compounds extremely attractive, however, somewhat difficult to strictly categorise: among the azoheteroarenes we find mainly nitrogen-based heterocycles such as pyrazole, pyrrole

• interesting results: in the case of derivative 63 containing pyrrole, capable of hydrogen bonding with the carbonyl oxygen (Scheme 20, left) [61][62], the E form is obtained almost quantitatively upon irradiation. In the case of pyridine-containing derivative 64 (Scheme 20, right) no photoswitching is

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• diverse C–N atropisomeric compounds possessing carboxamide, imide, lactam, sulfonamide, indole, pyrrole, imidazole, carbazole and amine skeletons have been reported by many groups [1][2][3][4][5][6][7][8][9]. C–N atropisomers are attractive compounds from the viewpoint of not only synthetic organic

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

• chiral INT-C, which, after imine-enamine tautomerization, led to the formation of final product 28. α-Acidic isocyanide-based transformations De novo arene formation In 2019, Zhu and co-workers developed the first example of catalytic enantioselective Yamamoto–de Meijere pyrrole synthesis [36][37

• Groebke–Blackburn–Bienaymé reaction. Construction of axially chiral 3-arylpyrroles via de novo pyrrole formation. Synthesis of atropoisomeric 3-arylpyrroles via central-to-axial chirality transfer. Dynamic kinetic resolution of bridged biaryls with α-acidic isocyanides. Desymmetrization of prochiral

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• the modular model 1c, with a vortex in the bond connecting the phenyl group with the pyrrole ring. Interestingly, paratropic ring currents are observed close to the molecular plane. This conclusion is reinforced by the NICS computed for the four rings of 1. As shown in Table 1, the isotropic NICS

• values at the molecular plane are always negative, but the pyrrole ring shows the lowest value. Indeed, if the NICSzz(0) values are considered, a paratropic character is observed at the center of the pyrrole and imidazole rings. The situation is more consistent when the NICS values are computed 1 Å above

• compound in the ground state. Since it is known that the aromaticity rules are reversed in 1ππ* excited states [28], the high fluorescent response of 1 is connected with its higher aromaticity at the excited S1 state. Actually, the two peripheric C–C bonds of the central pyrrole ring are slightly shorter

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• method for the synthesis of 3-arylbenzo[4,5]thieno[3,2-b]pyrroles has been developed via pyrrole ring annulation to the aromatic benzo[b]thiophene system, using 3-arylazirines as a N‒C=C synthon. The reaction is catalyzed by Ni(hfacac)2 and proceeds through the azirine ring opening across the N=C3 bond

• reactions of intermolecular annulation of a variety of non-aromatic five- [4][5][6] and six-membered carbo- and heterocycles [7][8][9] with azirines, which occur under transition metal catalysis or photocatalysis. Annulation of the pyrrole ring to an aromatic system is limited to reactions of functionalized

• reactions of heteroaromatics with azirines are known only for 2-chloro- and 2-sulfanylpyridines [14][15], which result in the formation of imidazo[1,2-a]pyridines (Scheme 1, reactions 4 and 5). To the best of our knowledge, no successful methods enabling the fusion of a pyrrole or azole ring to a 5-membered

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , Japan 10.3762/bjoc.21.119 Abstract The intramolecular oxidative fusion reaction of macrocyclic heteroaromatic arrays has provided strained polycyclic heteroaromatic macrocycles as promising functional molecules. In this study, we prepared an ortho-phenylene-pyrrole-thiophene hybrid icosamer, as the

• largest macrocycle ever synthesized is a dodecameric hybrid array of 1,2-phenylene, 2,5-thienylene, and 2,5-pyrrolylene units [22][23]. The intramolecular oxidative coupling of these arrays afforded heterohelicene-incorporated macrocycles D and E, depending on the relative arrangements of the pyrrole and

• thiophene units [24][25]. The influence of heteroaromatic positioning on the reaction outcome has been rationalized in our previous work [25]. As a further extension of this molecular design, herein we report the synthesis of an o-phenylene-pyrrole-thiophene hybrid icosamer and its oxidative fusion to yield

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• , thereby advancing their application in multifunctional chiral photonic and sensing platforms. In 2025, Gryko’s group synthesized a series of heterohelicenes 34a–c, featuring a 1,4-dihydropyrrolo[3,2-b]pyrrole (DHPP) core [48] (Table 10). The compounds exhibit similar absorption and emission profiles

• extended π-conjugation and distinct photophysical characteristics. Furthermore, they established a mild electrochemical protocol for synthesizing oxaza[7]helicenes incorporating pyrrole and furan units [87]. This method afforded products in 50–86% yield with Faradaic efficiencies up to 77%. Among them

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

• (necessary for aromatisation) are promoted by trifluoroacetic acid under similarly mild conditions. In case of the pyrrole synthesis, the same precursors are treated with a primary amine in DCM and the reaction mixture is heated at 40 °C for 12–24 h. As 1,4-addition also takes place during this process, two

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• absorption band. With respect to the phenyl group attached to the pyrrole nitrogen, the presence of the electron-withdrawing CF3 group led to a slight hypsochromic shift (4j). In the case of compound 4l, containing a 4-trifluoromethylphenyl group attached to the nitrogen, no significant shift of the

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• salt for further confirming their structures. A new synthesis of the related alkaloid brevicolline was also attempted from the same intermediate. However, after successful coupling of β-carboline with N-methylpyrrole, the trials to saturate the pyrrole ring under various conditions led to unexpected

• reactions: reduction of ring A of the β-carboline skeleton or trifluoroethylation of the pyrrole moiety occurred, leading to interesting and potentially useful derivatives. Keywords: alkaloid; β-carboline; Carex brevicollis DC; cross-coupling reaction; trifluoroethylation; Introduction Carex brevicollis

• debenzylated to brevicarine (2), isolated as a dihydrochloride salt. Müller et al. accomplished an alternative synthesis of brevicarine (2, Scheme 4) [23]. Compound 21 was obtained by treatment of nitrovinylindole 19 with N-methylpyrrole (20). Catalytic hydrogenation of the pyrrole ring and the nitro group of

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• -acting, potent tranquilizer with moderate duration, belonging to the triazolobenzodiazepine family [10]. It is derived through bioisosteric replacement of the benzodiazepine amide moiety with a triazole ring. Replacements of the benzene ring with thiophene and even with pyrrole are also known. Premazepam

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• bacteriochlorin for photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under far-red light (Figure 4) [43]. This synthetic bacteriochlorin, structurally modified from tetraphenylporphyrin with two reduced pyrrole rings, exhibits strong absorption in the far

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• cucurbituril [18], cyclodextrin [19], and calix[4]pyrrole [20], as well as flexible crown ethers [10][21]. Few two-dimensional (2D) shape-persistent macrocyclic compounds are used for this purpose. One difficulty in realizing 2D macrocycle-based orthogonal assembly is that the construction motif must be