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

• total synthesis – 2010 In 2010, Siegel and co-workers reported their total synthesis of complanadine A (Scheme 2). Their synthesis centres on two transition metal-catalyzed alkyne–alkyne–nitrile [2 + 2 + 2] cycloadditions to forge the two pyridine rings encoded by complanadine A [21]. Notably, the C2–C3

• reaction to rapidly establish the tetracyclic skeleton of complanadine A and an iridium-catalyzed site-selective pyridine C–H borylation followed by a Suzuki–Miyaura cross coupling to forge the C2–C3’ linkage. Their synthesis achieves a high degree of synergy between classic transformations and modern

• in 55% from 25 and 26 in three steps. Triflation of the pyridone gave 33 with a triflate at the C2 position for cross coupling to form the C2–C3’ linkage. At this stage, the Sarpong group needed to install a functional group at the C3 position of the pyridine. They creatively solved this challenge

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

• 82, followed by dehydrogenation, delivered compound 83 in 49% yield over three steps. Pyridone 83 could be funneled into pyridine 85 through O-triflation followed by Pd-catalyzed reductive detriflation. Ir-catalyzed meta-selective C–H borylation of 85, followed by bromodeborylation of the pyridine

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

• acted as nucleophile, the stable imine–gold–aryl cation–π–π interaction precluded rearrangement and promoted the capture of imine to form spiro[indoline-3,3'-pyridine] derivatives 67. The Ph3PAuCl/AgNTf2-catalyzed cyclization of N-propargyl-tethered amide enynes efficiently afforded four distinct

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

• 8-chloro-2,4-dimethyl-2H-benzo[e][1,2,3]thiadiazine 1,1-dioxide (4a, 7.10 g, 29.0 mmol) and pyridine (80 mL), hydrazine monohydrate (14.1 mL, 14.5 g, 290 mmol) was added dropwise. After refluxing for 26 h, the reaction mixture was evaporated to dryness, the residue was triturated with water

• , 20.5; IR (KBr) ν̃: 3407, 3360, 1477, 1302, 1151, 1106 cm−1; HREIMS (m/z): [M•]+ calcd for C9H12N4O2S, 240.0675; found, 240.0677. 8-Hydrazino-2-methyl-4-phenyl-2H-1,2,3-benzothiadiazine 1,1-dioxide (5b). To a mixture of 4b (4.00 g, 13.0 mmol) and pyridine (36 mL), hydrazine monohydrate (6.30 mL, 6.50 g

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

• electro-oxidative annulation of alkyne and benzamide afforded chiral pyridine-N-oxide [102], isoquinoline was synthesized successfully via electrochemical annulation of alkyne and benzamide [103] or imidate [104], electrochemical annulation of alkyne and acrylamide afforded α-pyrone and α-pyridone [105

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

• yield [83]. In their synthesis the cyclic acetal (2,5-diethoxy-1,4-dioxane-2,5-diyl)dimethanol or its dimethoxy analog was esterified with diphenyl phosphorochloridate in pyridine to give (2,5-diethoxy-1,4-dioxane-2,5-diyl)bis(methylene) tetraphenyl bis(phosphate). Subsequent removal of the phenyl

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• containing N-heterocycles, such as pyridine and pyrazole, provided the non-arylated tetrahydrofuran 12 as the main reaction product (Scheme 3), which is likely formed via the protodecupration pathway. However, to our delight the thiophenyl group was successfully added to the propargylsilane with 34% yield by

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

• representative substrate in two steps from benzoyl chloride, imidazole and methyl trifluoromethanesulfonate. In an initial reaction, this species was reacted under photoredox conditions in the presence of [Ir(dF(CF3)ppy)2(dtbpy)]PF6 (2 mol %, dF(CF3)ppy = 3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridine, dtbpy

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• steps, was converted into (R)-130 with 98% yield and 91% ee, which was subjected to a four-step sequence to give compound 131. In this reaction, catalyst 128 proved most effective. As previously reported [57], installing a sterically demanding or electronically influential group on the pyridine moiety

• enhanced the reaction performance. However, excessively bulky substituents at C4 and substitutions at both C4 and C5 hindered the coordination between substrate and catalyst, and led to reduced enantioselectivity. As to the structure of 128, the electronic effect of the bromo-substituted pyridine moiety

• hydroxy groups, the C18-alcohol was selectively protected by benzoylation using BzCN and 4-(dimethylamino)pyridine (DMAP) conditions, while the C19-alcohol was oxidized by TEMPO and N-chlorosuccinimide (NCS) subsequently. This two-step sequence provided ketoaldehyde 291 in 73% yield, demonstrating

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• ][21][22][23]. In addition to benzene-based systems, pyridine-embedded aza[1n]metacyclophanes have been synthesized by Wang [24]. Despite these advances, N-doped chiral macrocycles incorporating extended π-conjugated moieties remain largely underexplored. To date, only a few examples, carbazole-based

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

• furan and pyridine moieties were successfully synthesized with high enantioselectivity. These compounds would be challenging to access using alternative asymmetric methods. In 2025, our group disclosed a highly efficient catalytic enantioselective double annulation approach for the asymmetric synthesis

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

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

• , pyridine, and indole, alongside with less common oxygen and sulphur-based heterocycles such as thiophene, thiazole, oxazole. At the end of the section, we will also briefly discuss heteroarylimines which, although not being azo-switches, resemble the geometry of azo-compounds and possess similar

• ]. There is one known report of diazocines with heteroaromatic rings: an electron-rich aromatic ring (thiophene) gives a similar effect to what is shown for electron-rich substituents with a very poor 385 nm PSS (18%), while an electron-poor aromatic as pyridine does not affect the absorption properties

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• methylide [20]. generality and overall yields of the [2 + 3] cycloaddition of thioformylium methylide with azolones was not as effective. Possible alkylation of pyridine derivatives 1,3 and 4g by initial compound I did not allow us to obtain the corresponding products. A similar problem was observed for

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• alcohols and utilized in different metal-catalyzed asymmetric organic reactions [1][2][3][4][5][6][7][8][9]. In comparison with bisoxazoline ligands, relatively less attention has been paid to bisimidazoline ligands [10][11][12][13][14][15]. Some well investigated bisimidazoline ligands are pyridine-linked

• bisimidazoline (PyBim) ligands derived from pyridine-2,6-dicarbonitrile or pyridine-2,6-dicarboxylic acid and vicinal diamines, as analogues of pyridine-linked bisoxazoline (PyBOX) ligands [16][17]. They exhibited excellent performance in metal-catalyzed asymmetric organic reactions. Chiral rigid backbone-linked

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• of supramolecular vesicles using WP6 and pyridine derivatives (G1) (Figure 4). This supramolecular system achieves controllable assembly and disassembly through pH responsiveness: under acidic conditions (pH 6.0), protonation of the WP6 carboxyl groups leads to vesicle disassembly; whereas in a

• an example, SC4A encapsulates the pyridine group of AnPy with its electron-rich cavity, neutralizing the electrostatic repulsion of the cationic head group and promoting the close packing of the AnPy rings through hydrophobic interactions and π-π stacking, while its deprotonated phenolic groups

• binary vesicle system based on WP6 and SAINT molecules (G5), which exhibits multiple stimulus-responsive characteristics to pH, Ca2+ and temperature (Figure 20). WP6 and G5, as amphiphilic molecules containing pyridine groups and alkyl chains, form supramolecular amphiphiles through host−guest

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• configuration has been explained by the formation of a picolinium adduct, resulting from the trapping of the acidic by-product TMSOTf by the pyridine moiety of the picoloyl group during glycosylation [69]. The resulting intermediate, a picolinium-stabilized TMS-glycoside, exhibits high configurational stability

• the capture of acidic TMSOTf by the pyridine moiety of the picoloyl group [69]. The resulting picolinium-stabilized TMS-glycoside exhibits enhanced configurational stability due to the strong electron-withdrawing nature of the picolinium substituent, which effectively suppresses anomerization. This

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

• imidazo[1,2-a]pyridine components. In reaction A, an hyperhomodesmotic equation [19] 2 + 3 → 4 + 1 was defined, in which the conjugation of the bicyclic imidazo[1,2-a]pyridine unit was removed, while preserving the ortho-disubstituted phenyl ring, highlighted in yellow in Scheme 1A. This reaction yielded

• a stabilization energy of ca. 17 kcal/mol. In the alternative hyperhomodesmotic reaction B, defined as 5 + 6 → 7 + 1, the formal ten-electron Hückel aromaticity of the imidazo[1,2-a]pyridine moiety (in blue) was preserved while the phenyl component was decomposed. The computed stabilization energy

• -phenylene moiety in the tetracyclic structure. Combination of reactions A and B in the form yields an average value of ⟨ΔEAB⟩ = −22.6 kcal/mol. A similar treatment of the separate components as outlined in reactions C and D shows a much lower stabilization energy for imidazo[1,2-a]pyridine 8 and a higher

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

• ). Benzothienopyrrole 3b was methylated using the MeI/NaH system into 1-methyl-substituted derivative 6 in 81% yield. With the same efficiency, when compound 3b was treated with di-tert-butyl dicarbonate in the presence of 4-(dimethylamino)pyridine (DMAP), Boc-derivative 7 was obtained. Finally, the formylation of 3b

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

• . Similarly, 4-methylpiperidine and N-tert-butoxycarbonylpiperazine afforded the corresponding enaminones 9i and 9j, respectively, in moderate yields. Gratifyingly, 1-(pyridin-2-yl)piperazine was also tolerated, providing the expected product 9h in 46% yield. Considering that pyridine is one of the core

• components of drug derivative formulations, present in more than 7,000 active pharmaceutical compounds [43], the possibility of introducing a pyridine ring into the enaminone structure could be useful for the development of new drug candidates. When pyrrolidine was used as amine reagent, the target enaminone

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

• ]. These oxetanone precursors are generated from easily accessible alkynylphosphonates 124 via gold-mediated alkyne oxidation by pyridine N-oxide 125 followed by a formal O–H-insertion of the resulting metallacarbene intermediate 128. The optimised procedure requires 5 mol % loadings of the gold catalyst

• to a potentially even larger library of amide isosteres. The scope of the carbon nucleophiles is very broad and includes alkyls, alkenyls, alkynyls, aryls and heteroaryls (e.g., pyridine, indole, thiophene), as well as (poly)substituted phenyls bearing a nitrile or halogen(s). On the other hand, the

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• a central role in this photocatalytic system. This strategy demonstrated good chemical selectivity for the functionalization of pyridine and alkanes, resulting in 55% to 86% yields of products 38, 39, 40, and 41, respectively. Amidyl radical from N–O bond cleavage In 2022, Alexanian’s group

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

• heteroaromatics are rare due to the limited synthetic methods available, although some N- or BN-nanographenes are known. An efficient synthesis of azulene−pyridine-fused heteroaromatics was reported by Swager and co-workers (Scheme 23) [105]. A series of monoazulene PAHs 174a–e was obtained from 1-nitroazulene

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

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• activation [34]. Overview of the predictive workflow: For the shown substrate on the left, three unique activation sites are possible (labelled “Ha−c” with two directing groups, a pyridine (blue) and an oxime-ether (red) group. The latter has two potentially directing atoms, nitrogen and oxygen. The

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• activities [9][10]. Imidazo[1,2-a]pyridine and isoquinolinone-kind scaffolds are privileged rings which can be found in drug molecules such as zolimidine [11], zolpidem [12], alpidem and antiemetic drug 5-HT3A antagonist palonosetron [13] (Figure 1). Imidazopyridine-fused isoquinolinones have been developed

• as HIV inhibitors [14]. The imidazo[1,2-a]pyridine ring can be readily synthesized by the GBB reaction [10][15], while the isoquinolinone ring is commonly generated by a cyclative lactamization process. Performing a GBB reaction followed by an intramolecular amidation is a good approach for making