Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• [29][31]. A one-pot reaction of submacrocycle 1a and 2-(benzyloxy)benzene-1,3-diol (2a) in the presence of 8.0 equivalents of CsF yielded the ultracycle precursor compounds. Three reorganized products B4a, B5a, and B6a with different ring sizes were isolated. As previously observed, the structural

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• accessibility of these bioactive compounds for pharmaceutical applications. Keywords: amino acids; hydantoin; microwave-assisted; one-pot reaction; Urech synthesis; Introduction The hydantoin moiety is a scaffold found in many biologically active compounds exhibiting a diverse range of properties, including

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• ; heteropolycycles; multicomponent reactions; one-pot reaction; Introduction Copper has gained a relevant role in organic synthesis as an alternative to precious metals due to its low toxicity, ease of handling, high catalytic activity, and cost-effectiveness [1][2]. In recent years, Cu(OTf)2 has significantly

• ]quinolinones 42 was achieved via the one-pot reaction of tetronic acid, 5-aminoindazole and arylaldehydes under copper catalysis and ultrasonic irradiation, in acetonitrile as solvent. The mechanism involves a Knoevenagel condensation between the tetronic acid and the arylaldehyde as first step, followed by a

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• : isocyanide; multicomponent reactions; one-pot reaction; oxidation; spiroindolenine; Ugi reaction; visible light; Introduction Diversity-oriented synthesis (DOS) is a successful approach to biologically active scaffolds directed to create an enormous exploratory space in pharmaceutical hit discovery [1][2

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• formation of alkenone intermediates, dialkyl acetylenedicarboxylates 147, as alkynoyl derivatives, are transformed to pyrazolones 149 by Michael addition–cyclocondensation with phenylhydrazine. In a consecutive one-pot reaction, the latter intermediates undergo O-acylation with aryl chlorides to give N

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• -bromoethyl)benzaldehyde 79 was utilized to form the highly reactive cyclic iminium intermediates 81 through the condensation with amidines 80. The subsequent formal [4 + 1] cycloaddition with the isocyanide and the 1,3-H-shift occurred to afford pentacycles 82. Performing the one-pot reaction under the

• products 109, formally derived from a GBB reaction with aromatic isocyanides and benzaldehydes. The same approach was used by Jalani and Jeong [70] where p-TsOH served as the catalyst for the one-pot reaction. A library of 21 examples of 109 were produced in 41–78% yields. Various functional groups were

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• thermophilum and Thermomyces lanuginosus fungi. The activity was related to the presence of fluorine atoms, and the substitution of -NH with trifluoroacetyl group achieved the most active compound. Spirothiadiazine steroids Novel steroidal spiro-1,3,4-thiadiazines have been recently described through a one-pot

• reaction on 16β,17β-epoxypregnenolone (156), synthesized via a four-step process from 16-dehydropregnenolone acetate (155) [65]. Initially, the nucleophilic ring opening of the oxirane with substituted oxamic acid thiohydrazides led to a non-isolated intermediate hydrazone ii. Since both NH and SH are

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• via copper-catalyzed cross-coupling [29] with an electron-rich aryl substituent was exemplarily conducted to further expand the scope of possible products (see Scheme S2, Supporting Information File 1). We also investigated the scope and limitations of a one-pot reaction for the triazene cleavage and

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• preparation of the Grignard reagent followed by the homo-coupling reaction. Various conditions were examined and biphenyl (3b) was obtained in 85% yield in a one-pot reaction, when bromobenzene (5b) was treated with 1.5 equiv of Mg (turnings, grade for Grignard reaction) under reflux conditions of THF for 24

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• triethylamine in methanol afforded benzocoumarines 18a–ac (Scheme 4) [33][34]. The formation of the product, which was obtained in a two-step one-pot reaction, can be explained by a mechanism similar to the one discussed for the formation of 17. 1,4-Addition gave intermediate D which was isolated, but used in

• of DBU afforded furo[3,2-b]chromen-9-one 36a in 32% yield. Based on this observation, the two-step one-pot reaction of ketoamides 34a–f with 3-halochromones 15a–c was studied which afforded furo[3,2-b]chromen-9-ones 36a–f, albeit, in only low to moderate yields (Scheme 19) [41]. The formation of

• . Similarly to products 35, relatively low yields were observed for reactions of methoxy-substituted 3-halochromones. The two-step one-pot reaction of N-unsubstituted ketoamide 33a with 3-halochromones 29a and 31a afforded spirocycles 36a,b, albeit, in only moderate yields (Scheme 20) [41]. The formation of

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• tetrazolyl-1,2,3,4-tetrahydroisoquinoline 8a in 74% isolated yield which is higher than the one-pot Ugi/Hecke reaction to give product 6b (58%). Under the alternative one-pot reaction conditions involving an N-alkylation step, the substrate scope was explored by the preparation of 10 derivatives 8a–j (Scheme

• scalability of the two-step one-pot reaction protocol, we performed the synthesis of tetracyclic tetrazolo-pyrazino[2,1-a]isoquinolin-6(5H)-one 6c in gram quantity from 10 mmol of 1a which led to the formation of product 6c in a satisfactory yield 77% (Scheme 6). The products 6 and 8 were characterized by 1H

• . The initial Ugi-azide four-component reaction constructs the tetrazole motif while the subsequent intramolecular Heck reaction assembles the tetrahydroisoquinoline. The one-pot reaction avoids the intermediate purification which has favorable PASE in the synthesis of heterocyclic compounds

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• -pot reaction was performed by adding sodium 4-methylphenylsulfinate in the first step which was followed by NaN3. As the result, the formation of hydrolysis product 5a and 2,4-diazidoquinazoline (6a) was observed. Next, the reaction 1a → 4a in DMSO yielded diazidoquinazoline 6a as a major product and

• first attempts in iPrOH did not provide the starting material conversion. The reaction in THF resulted in the full conversion of the starting material, but the analysis of the crude product revealed the quantitative formation of hydrolysis product 5a. Assuming the instability of intermediate 2a, a one

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• -di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4. 6,8-Di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 prepared by the one-pot reaction between 6,8-di-tert-butyl-3H-phenoxazin-3-one (1) and aromatic amines 2b (the yield is given in parentheses). Synthesis of 14H-quinoxaline[2,3-b]phenoxazines 5

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• one-pot reaction involving TCNE and one equivalent of 3-(4-(dimethylamino)phenyl)propionitrile in toluene at 90 °C for 24 h. Subsequently, one equivalent of 1 was added at 90 °C for 24 h (Scheme 6) [101]. While the separation of the isomers was not achieved, the structure of the 3Z,5E isomer was

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• , this new method creates two C–N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste. Keywords: carbazoles; heteroaromatics; iodanes; metal-catalyzed; one-pot reaction; Introduction N-Acyl carbazoles are effective

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• the construction of various nitrogen-containing polycyclic frameworks (36, 38, 39, 41) (Scheme 17) [32][33][34]. These protocols offered a wide range of substrate compatibility in a one-pot reaction, significantly enhancing synthetic efficiency. Nitrogen-containing heterocycles are abundantly found in

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• maleimides in MeCN at 110 °C for 6 h afforded the corresponding monocycloaddition compounds followed by acylation to yield intermediates 22. The subsequent sequential Staudinger/aza-Wittig reaction of intermediates 22 gave products 23a–g in 48–75% yields with 5:1 to 6:1 dr (Scheme 14). This one-pot reaction

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• notable distinction as they could readily undergo oxidation to yield the corresponding crownphyrins 28–33, incorporating a dipyrrin unit. The synthetic pathway towards crownphyrins is straightforward and relies on a one-pot reaction between diformyldipyrromethane 20a/b and a diamine which introduces the

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• substituent undergo a one-pot reaction with reasonable efficiency and furnished the expected 1,2,3-triazole derivative 7 in 61% yield under the approved conditions. Next, we turned our attention to the generation of divalent systems, starting with the reactions of 1,3- (8) and 1,2-bis(bromomethyl)benzene (11

• . One-pot reaction employing enantiopure alkynyl-substituted 1,2-oxazin-4-one derivative 6 leading to 1,2,3-triazole 7. One-pot reactions of dihalides 8 and 11 with sodium azide and alkyne 2 leading to symmetric divalent bis(1,2,3-triazoles) 9 and 12 as major products. One-pot reactions employing

• enantiopure alkynyl-substituted 1,2-oxazin-4-one derivative 6 leading to bis(1,2,3-triazoles) 14 and 17 as major products. One-pot reaction employing enantiopure alkynyl-substituted 1,2-oxazin-4-ol derivative 19 leading to bis(1,2,3-triazoles) 20 and 21. Reductive ring-openings of 1,2-oxazine derivatives 19

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• ; multicomponent synthesis; one-pot reaction; trichloroacetic acid; Introduction π-Conjugated porphyrin macrocycles are known for their applications in numerous areas ranging from oxygen transport, photosynthesis, catalysis and medicine [1][2][3]. In the past several years, diverse organic scaffolds have been

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• products (e.g., 7) whereas irradiation with blue light (λ = 455 nm) provided disubstituted products 8 (Figure 5A). Additionally, adding a different trapping reagent before switching from green to blue light allows for a sequential and controlled substitution in a one-pot reaction (Figure 5B). 2,4,6

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• for the construction of biologically interesting highly diversified pyrazole-linked thioamide and amide conjugates has been developed. The pyrazole C-3/4/5-tethered thioamide conjugates were prepared via a one-pot reaction between highly diversified pyrazole carbaldehydes, cyclic secondary amines, and

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• substituents in the one-pot reaction and showed that regardless of the substitution pattern, the reactions lead to the stereoselective formation (≥95% (2E,4E)) of the respective dienones under mild conditions. It was found that enynes with alkyl chains gave higher yields than the corresponding aryl-substituted

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• intermediate before the click reaction was established by 1H NMR analysis of the reaction mixture). However, the product of this two-step, one-pot reaction (19) was isolated in respectable 61% yield. The structure of compound 19 was confirmed by the single-crystal X-ray analysis which demonstrated that the