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

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• diol desymmetrization of ent-28 was best achieved with Amano lipase PS (PSL), yielding monoacetate ent-37 (de 99.6%, 93% yield) without the formation of diacetate ent-39. Compound 37 was tosylated using tosyl chloride in pyridine with the addition of DMAP and the resulting product was treated with

• to afford the corresponding sulfone 41. However, Uguen found that a more efficient route involved treating alcohol 40 with tosyl chloride in pyridine and DMAP, followed by nucleophilic displacement with sodium thiophenol and oxidation of the resulting sulfide with m-CPBA, yielding sulfone 41 in 85

• acetate functionality using potassium carbonate in methanol, followed by reaction with tosyl chloride in pyridine and DMAP. The product, ent-43, was obtained in 79.5% yield over three steps. This compound was reduced using LiAlH4 and treated with TBAF to remove the TBDMS group, yielding alcohol ent-40 in

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• applications in organic reactions. Similarly, Kunishima and co-workers (2021) utilized (N,N’-dialkyl)triazinedione-4-(dimethylamino)pyridine (ATD-DMAP) for the amidation of cinnamic acid (7) to generate the corresponding amide 10 in excellent yield (Scheme 5B) [37]. Mechanistically, the carboxyl group attacks

• group (2024) also investigated BH3·pyridine to catalyze amidation reactions with lower catalyst loading (Scheme 40B) [77]. Whiting and co-workers (2019) also used boranes to catalyze the direct amidation of carboxylic acids. In this work, they co-polymerized styrene, divinylbenzene and

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• in triarylmethyl radicals is by touching the triphenylmethyl scaffold itself, rather than only its substitution pattern. A variety of studies have been concerned with the pyridine-diphenylmethyl (PyBTM) motif, which has one of the para-carbons replaced by a nitrogen (see Figure 3) [56]. Surprisingly

• character of the fluorine substituent. When gold atoms are coordinated to the pyridine nitrogen, a ϕ as high as 8% has been observed [57]. The reason for this increase in ϕ to 8% for Au-Cl2PyBTM and 20% for Au-F2PyBTM is unknown, but the increase in the presence of a heavy atom might point at an improved

• the hole will reside on the mesityl and phenyl units (HDMO) and the electron resides on the PyBTM core (SOMO) (see Figure 4b). Instead of pyridine also carbazole (Cz) units have been coupled to produce N-carbazolyl-bis(2,4,6-trichlorophenyl)methyl radicals (CzBTM) (see Figure 5a). ϕ is highest at λem

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• Reaction exploration began with (E)-hex-3-en-1-yl methoxycarbamate, prepared in good yield from widely available trans-3-hexen-1-ol (Table 1) using a two-step protocol (1. 1,1’-carbonyldiimidazole (CDI), CH2Cl2; 2. MeONH2·HCl, pyridine) [33]. Based on insights from our work with I(III)-promoted alkene

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• achieved by using (R)-BTM (19), furnishing acetate 18 with satisfactory efficiency and enantioselectivity (37% yield, 85% ee). Finally, iodination of 18 employing Johnsen’s protocol (I2, pyridine) [39] provided α-iodoenone 13 in 89% yield. On the other hand, the synthesis of acetal aldehyde 14 commenced with

• 11 in the presence of AcOH by exposure to UV-light at 254 nm occurred exclusively to provide an inseparable mixture of 32 and 33 (Table 1, entry 5). Subsequent dehydration of the resultant mixture with SOCl2 and pyridine yielded separable enones 34 (51%) and 10 (9%) over two steps. The structure of

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• structurally diverse macrocycles through the dynamic self-assembly of α,α’-linked oligopyrrolic dialdehydes and alkyldiamines (Scheme 10) [39]. Their investigation revealed distinct solvent-mediated selectivity in product formation. Condensation of the pyridine-bridged oligopyrrolic dialdehyde 37 with simple

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• coupling reaction of phenylpyridine with dialkylphosphonate in the presence of palladium. It should be noted that the presence of palladium is an essential factor, and the results showed that the coupling reaction failed in the absence of palladium. Under pyridine-mediated conditions, the reaction follows

• carried out in a divided cell using platinum electrodes as the anode and cathode in the presence of pyridine as a base and ligand (Scheme 14). The catalyst behavior of palladium is attributed to its ability to form palladium clusters of specific sizes that exhibit high catalytic activity. However, this

• corresponding phosphorylated propargyl alcohols (Scheme 19). The reaction yield showed that this method is not sensitive to electron-withdrawing or electron-donating groups at different positions on the aromatic ring. Most likely, the 3-substituted pyridine substrate and the enynes with nitro or carbonyl groups

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• previously [70]. Saponification of TetW1OAc with LiOH at 50 °C followed by acidification with 0.1 M HCl gives TetW1 in 69% yield [70]. Finally, the sulfation of TetW1 occurs upon treatment with py·SO3 (20 equiv) in dry pyridine to yield C1 as a white solid in 68% yield. In accord with the depicted C2v

• pyridine sulfur trioxide (1.1838 g, 7.437 mmol) was dissolved in dry pyridine (57 mL). The resulting mixture was heated at 90 °C under N2 for 18 h and then cooled to rt. The precipitate was collected by first decanting some of the solvent and then the remaining mixture was transferred to a 50 mL centrifuge

• , 10 min). The crude solid was analyzed by 1H NMR which showed residual pyridine. The crude solid was subsequently dissolved in water (150 mL) and re-precipitated by the addition of EtOH (144 mL) followed by centrifugation (7200 rpm, 5 min) to obtain a white solid. The solid was dried overnight under