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

• in four steps. Subsequent conjugate addition of the lithium anion of TMS-acetonitrile to 15, followed by careful one-pot protonation of the resulting enolate with ethyl salicylate and TMS removal with CsF, gave 16 bearing three properly arranged substituents. Grignard 1,2-addition to ketone 16

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

• also observed in Yang’s total synthesis of (+)-cyclobutastellettolide B (13) as described above [21]. The driving force for the rearrangement is proposed to stem from 1,2-strain between the substituents at C13/C10 and C13/C7, consistent with observations from Yang's work [21]. Next, peroxides 54a and

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

• along with comparator H2 as solid-state sequestrants for a panel of five dyes (methylene blue, methylene violet, acridine orange, rhodamine 6G, and methyl violet 6B). We find that catechol-walled H2 (OH substituents) is a superior sequestrant compared to G2W1–G2W4 (OMe substituents). X-ray crystal

• substituents – performs significantly better than G2W2 and displays very good removal efficiency for methylene violet. Previous researchers have shown that dye adsorption is promoted by hydroxy, carbonyl, methoxy, and aldehyde substituents which provides an explanation for the better performance of G2W1

• relative to G2W2 [48]. Quite surprisingly, the removal efficiencies for H2 are notably higher than G2W4 for all five dyes studied. These differences are particularly noteworthy given that H2 and G2W4 are constitutional isomers and differ only in the swapping of methoxy substituents (G2W4) for hydroxy and

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

• tolerated a range of substituents on the olefin, giving the products with high enantioselectivity. Reactions of chiral β-methyl-substituted aldehydes 11 and 12 with indene (13) yielded tricyclic products with good diastereoselectivity and particularly high optical purity (99% ee). Organo-SOMO catalysis was

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

• substituents serve as critical switches for determining reaction pathway selection. Chemists have developed sophisticated synthetic strategies for programmable assembly of complex small molecular framework by leveraging substituent electronic and steric effects. In 2006, the Shibata group reported a gold

• under gold(I) catalysis through a substituent-controlled strategy (Scheme 8) [15]. Substrates with heteroaryl substituents underwent 6-endo-dig cyclization via gold-heteroatom coordination, furnishing the lactone-fused pyran scaffold 34 (Scheme 8, path a). Substrates with aryl substituents at the

• al. (Scheme 11) [18]. The pathway selectivity was regulated by modulating substituents on the terminal alkyne. When the alkyne was unsubstituted, the vinylidene intermediate 48 was generated via a 5-exo-dig cyclization, which subsequently underwent protonolysis to yield the bicyclo[3.2.1]oct-2-ene

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• contrast to classic Buchwald–Hartwig couplings – aryl bromides with substituents at the ortho-position (3a and 3c–g) are more reactive than those with substituents at the para-position (3b and 3h–l). This difference might be explained by steric repulsion, which may favor C–N-bond coupling with the terminal

• efficiency, as the reaction proceeds smoothly even when both coupling partners possess sterically hindered substituents at the 2,6-positions. For example, the coupling of 2,6-difluorophenylhydrazine with 1-bromo-2,6-dimethoxybenzene yielded tetra-ortho-substituted azobenzene 5a in a notable yield of 63

• )–aryl intermediate (B). Subsequently, ligand exchange occurs, generating hydrazido complexes C and C'. When bulky substituents are present on the phosphine ligand and/or (both) coupling partner(s) has ortho-substituent(s), the hydrazido complex C, chelating on the terminal nitrogen, is preferentially

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

• , empirical approaches based on 1H NMR anisotropy method have gained attention as alternative strategies for stereochemical assignment of chiral molecules. Among these, the modified Mosher method, which utilizes the ring current effects of aryl substituents, has been extensively applied to chiral alcohols [2

• )-2a. This inversion of Cotton effects is due to the difference in steric features between the two substituents of amines: methyl and hydroxymethyl group in (S)-2a, and isopropyl and hydroxymethyl group in (S)-2b. The CD spectra of 1–(S)-2-phenylglycinol conjugate (S)-2c showed the same sign for the

• reasonably predicted by simply evaluating the relative steric bulkiness of substituents near the amine moiety. The relative substituents’ priority is determined not by the CIP rule, but by the steric bulkiness of substituents. On the other hand, for quaternary amines, it was difficult to assess the relative

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

• % 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

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

• introduction of substituents to the seven-methine carbon chain of Cy7 influences its optical properties and ability to interact with biomolecules. A one-pot synthesis of γ-acyloxy-Cy7 from renewable furfural, simple anhydrides, and a quaternary ammonium salt under smooth conditions was reported (Scheme 63

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

• electrophilic reagents. This site offers a strategic handle for introducing diverse substituents to modulate the compound's properties. Although the indolo[1,2-c]quinazolin-6(5H)-one scaffold offers considerable potential for structural diversification, current literature describes only the arylation at

• towards all tested cancer cell lines. However, no clear correlation between structure and activity was observed. For example, elongation of the alkyl substituents (N,N-diethylamino derivative 9b) led to a complete loss of antiproliferative activity, while its cyclic analog 9c showed the lowest IC50 value

• emergence of antiproliferative activity, which is not strongly affected by the structure of the terminal cyclic amine. Replacement of the substituents from position 12 to position 6 of 6-methylindolo[1,2-c]quinazoline core (compounds 14a–d) leads to increased cytotoxicity compared to the initial structure

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• form a cis-substituted tetrahydrofuran (THF) moiety fused to the lactone with higher oxidation states. Notably, the phenyl ring contains three oxygen substituents in the form of alcohol and methoxy groups at different positions. Biosynthetically, the THF ring was supposed to be formed through a

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• approaching two years, significantly exceeding the reported storage lifetime of other azobenzene-based solar thermal fuels. Han et al. synthesized a series of bisazobenzene small molecules with various substituents [90], all exhibiting photoinduced solid–liquid phase transitions. In contrast, comparable

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• formation of heterocyclic systems in a minimal number of steps and offer several ways to vary substituents and they are widely used in drug discovery and development, as well as in diversity-oriented synthesis [1][2][3][4]. In addition, the application of condition-based divergence strategy [5] and the

• I–VI were formed (Scheme 1) [8][18][19]. It is known that substituents in aminoazoles can significantly influence their behavior in multicomponent heterocyclization reactions [4][8][20][21]. However, the reactions of 5-amino-1,2,4-triazoles containing substituents in position 3, which can also

• -aminotriazoles 1a,b having pronounced electron-donating substituents (methylthio- and methoxy groups). On the other hand, the MCR of the reagents 1a, 2a–c and 3 under ultrasonic irradiation for 2 h at room temperature (25 °C) (Scheme 3) afforded a mixture of 5-(2-hydroxyphenyl)-2-(methylthio)-7-((3-(methylthio

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• , and the stereochemical-defining substituents. The indices can be generated based on analysis of the chemical structures of the starting materials and products, without mechanistic insights of the transformation. Representative examples of reactions that establish point chirality, axial chirality

• molecule is characterized by the absence of mirror planes and centers of inversion. Central chirality arises when four distinct substituents (a, b, c, and d) are arranged tetrahedrally around a central atom (Scheme 1A). Non-central chirality – such as axial and planar chirality – are becoming increasingly

• within three-dimensional molecular frameworks that restrict conformational freedom. The geometric scaffolds can be a central atom, an axis, or a plane, and the combination and spatial arrangement of chemically distinct substituents establish the stereogenicity. Therefore, despite the apparent differences

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

• -donating substituents demonstrated higher yields (p-Tol > p-BrC6H4) (Table 2, entries 3 and 4). The p-bromo-substituted iodane I-6, albeit in a more modest yield, gave the diene 10d with 98:2 selectivity. Switching to the more sterically challenged triisopropylsilyl (TIPS) group (Table 2, entry 2) resulted

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

• 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

• from diester 157, underwent enantioselective monobenzoylation with complex 159 as catalyst to form benzoate 160 in 90% yield with 90% de. The size of the C4-substituent in the oxazoline moiety crucially influenced the enantioselectivity and conversion of the reaction: smaller substituents reduced the

• differential ability between two hydroxy groups, while bulky substituents hindered the formation of coordination bonds between the substrate and catalyst. As previously reported, with a suitable substituent at C4, an additional C5-substituent slightly enhanced the catalytic performance of the complex [62]. For

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

• revealed the formation of isomeric products depending on the substituents on the N atoms. Notably, two intrinsically chiral macrocycles MC1 and MC3 with C1 symmetry were successfully obtained. These macrocycles exhibit exceptional photophysical properties, particularly remarkable high fluorescence quantum

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• products with complete stereoselectivity. Substrates bearing electron-donating or electron-withdrawing groups on the aromatic rings provided good to excellent yields, indicating that both types of substituents are well tolerated under the reaction conditions. Although modest yields were obtained under flow

• (0.125 M), were then applied to evaluate the scope of the reaction. Under these conditions a small library of chiral enantiopure tetrasubstituted piperazines 2b–j bearing both electron-withdrawing and electron-donating substituents, was synthetized. The results are summarized in Scheme 5. The chiral

• ), as well as electron-donating groups like methoxy (2f), aryl/alkyl (2h,i), and alkenyl substituents (2e), were well tolerated. Notably, the sterically hindered derivative 2h was isolated with the highest yield of 87% indicating that bulky ortho-substituents on the aromatic rings do not influence the

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

• and polycyclic ketone 2, they achieved the efficient asymmetric synthesis of various helically chiral azahelicenes 3 (Scheme 1). To address the inherent length-scale challenges of molecular helicene frameworks, the authors designed and synthesized novel CPAs bearing extended π-substituents at the

• ortho-positions. The dual hydrogen-bonding interactions were critical for this reaction, ensuring that the reaction proceeded within the chiral pocket of the CPA catalyst. Moreover, the authors proposed that the extended π-substituents at the ortho-positions of CPA could engage in π–π-stacking

• component, which facilitated the asymmetric synthesis of substituted [5]- and [6]pyridohelicenes 15 with ortho-phenolic substituents in position C1 with high enantioselectivity (Scheme 4) [21]. Notably, utilizing one equivalent of DDQ for semioxidation of the tetrahydroquinoline product of the Povarov

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• overall surface tension. Along with reduced conversions, we also found that our anticipated trend in catalyst efficiency, i.e. increasing conversions with the increasing lipophilicity of the carbamate substituents, was not consistently followed (Table 2B). While conversions increased going from no

• extent of alkyl grafting, the –CH2– content in the pores of KSU-1n-Hex and KSU-1C14 is still greater than for KSU-1iPr and KSU-1t-Bu, assuming a uniform distribution of alkyl chains. Additionally, although the introduction of large alkyl substituents in a MOF is associated with a reduction in pore

• , Supporting Information File 1). We found that the conversions were significantly better than those reported for H2BDC-NH2 under more forcing conditions (60 °C, 6 h) [52], which makes sense given that the methyl substituents on the carboxylate increase the basicity of –NH2, which should increase the catalytic

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

• with a photoswitch, several factors must be considered: substituents, temperature, and solvent strongly affect the photophysical properties. For instance, the presence of electron-withdrawing (for instance -Cl, -Br, -CN, -NO2) and electron-donating groups (-alkyl, -OR, -NR2), which are directly

• tautomerism is an intermolecular process that depends not only on the choice of aryl rings and substituents but also on concentration, solvent polarity, and the presence of proton sources [5][15]. In conclusion, the choice of aryl rings, substituents, and substitution position are all crucial to determine the

• -phenylazopyrazoles notably increased the half-lives with respect to the unsubstituted ones, probably a result of favourable weak interactions between the pyrazole ring and the ortho-substituents in the Z-form [30]. Despite the high intensity of the nπ* absorption band, the absorption spectra of the two isomers are

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• this methodology. As summarized in Scheme 2, we initially investigated the scope and effect of arylamine functionalities on this transformation. Under optimized reaction conditions, arylamines bearing either electron-rich or electron-deficient substituents at the para-position demonstrated good

• with 3m′ and 3n′ in high yields. Slightly lower yields were observed when styrenes bearing electron-withdrawing substituents (2d and 2f) were examined, giving the final products ranging from 56% to 75% isolated yields. Nevertheless, meta-substituted styrene (2g) was also evaluated in this reaction

[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

• relative configuration (cis or trans) of the substituents. Therefore, the structures of the obtained compounds were determined by single crystal X-ray analysis (Figure 1). Thus, all the obtained derivatives of oxo-rhodanine 6, rhodanine 8 and imidazolone 9 had a cis configuration, while the derivatives of

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

• different substituents on the NH moiety of the imidazoline ring. Herein, we designed and synthesized several sulfonylated cyclohexane-1,2-linked bisimidazoline (cHBim) ligands (Figure 1). Results and Discussion The synthesis of the chiral cyclohexane-linked bisimidazoline ligands started from enantiopure

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• polarity, with these effects varying based on the amount, position, and orientation of the fluorine substituents [7][8]. Mondal and colleagues have extensively reviewed additional properties of fluorinated cyclopropanes, including the conformational behavior of substituents attached to a fluorinated