Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• , and the successful late-stage electrohydrogenative functionalization of structurally complex molecules and drug derivatives further underscored the practical applicability of this strategy in medicinal chemistry contexts. To probe the involvement of catalytically relevant Fe–H species, radical probe

• exhibits a broad substrate scope, high efficiency, excellent functional-group tolerance, and consistently high levels of deuterium incorporation (Scheme 5Bi) [100][101]. Notably, the transformation proceeds efficiently with derivatives of biologically active molecules, such as serine and niflumic acid

• , the desired succinic acid derivatives were obtained. Importantly, this efficient conversion was observed only in the presence of the mediator; in its absence, product yields were markedly diminished and substantial amounts of starting material remained unreacted. According to the proposed mechanism

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• -tetraethylpiperidine (TEEPONE). Keywords: heterocyclization; piperidine nitroxide; TEEPONE synthesis; Introduction Since their discovery in 1959 by Lebedev and Kazarnovsky, stable nitroxides of the piperidine series (2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) derivatives) hold a prominent position as compounds of

• radicals are based on approaches employing either the tetraethyl analog of phorone or acetonine [11][15][17][18] or the desulfurization of dispirothiapyranone derivatives [19][20][21][22]. Consequently, the structural diversity of radicals bearing acyclic substituents is practically limited to derivatives

• nitroxides 7a–d in 50–80% overall yield from piperidines 5a,b (Scheme 3). The structures of nitroxides 7a–d were confirmed by 1H NMR spectroscopy of their amine derivatives, obtained via Zn/CF3COOH reduction in CD3OD, following a reported procedure [37]. The full line-shape analysis of the 1H NMR spectra for

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• -Michael addition [13][14][15][16][17][18]. In such cases, the reaction provides direct access to β-amino carbonyl derivatives and related motifs that serve as versatile intermediates in synthetic and medicinal chemistry. Despite its conceptual simplicity, catalytic hydroamination remains challenging. This

• using an inexpensive CuCl catalyst in combination with electron-donating phosphine ligands (L1, L2) or NHC salts (L3, L4) and KOt-Bu [37]. Various aromatic amines and heteroaromatic N–H nucleophiles reacted efficiently with electron-deficient alkenes 2, such as vinyl sulfones, acrylonitrile derivatives

• significantly affecting the reaction efficiency. In addition to simple anilines, diverse heteroaromatic amines including indole, pyrrole, triazole, carbazole, and imidazole derivatives participated effectively in the copper-catalyzed conjugate addition, providing the corresponding β-amino products 3 in high

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• challenging synthesis of 5,6-carboxylated SiR derivatives, which are essential intermediates for bioconjugation. Here, we report a practical CO2-mediated strategy for the synthesis of 5,6-carboxylated SiRs from brominated SiR precursors via lithium–halogen exchange and direct carboxylation. Using n-BuLi and

• readily available CO2, this method delivers carboxylated SiR derivatives in 60–93% yields while avoiding the use of t-BuLi, toxic CO, and expensive palladium catalysts. In addition, the crude carboxylation mixtures can be directly subjected to amide coupling without chromatographic purification, enabling

• makes SiRs highly attractive as fluorogenic probes for precise super-resolution imaging by enabling target-specific recognition and significantly improving signal-to-noise ratio (SNR). In addition, hydroxymethyl-substituted SiR derivatives, including HMSiR [30][31] and Aze-HMSiR [32][33][34], can

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• intriguing moiety in biologically active compounds (e.g., natural products used for medicines, quinine, and quinidine [5][6][7]) and synthesized pharmaceutical agents (e.g., quinolone antibiotics [8]). Moreover, quinoline-2-carboxamide derivatives are used as ligands in organic synthesis owing to their high

• preparation of annulation precursors through o-brominated aniline derivatives [36][37][38][39][40][41]. Furthermore, the reported methodologies for synthesizing N-heterocycle-fused lactams are characterized by either low efficiency or protracted processes [42][43]. On the other hand, benzocyclization

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• (Scheme 6). However, attempts to cyclize them using the benzoyl group to form 4H-furo[3,2-b]pyrrole derivatives were unsuccessful. Triflate 7a is obtained from pyrrole 5a by treatment with Tf2O in 85% yield, but it proved inert in the Suzuki reaction with 4-chlorophenylboronic acid and 2-(4,4,5,5

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• synthesis, neurotransmitter function, and regulation of acid-base balance, metabolic intermediates, and promotion of nutrient absorption [4]. Therefore, the synthesis of substituted glutamic and pyroglutamic acid derivatives is vital to medicinal chemistry. In our previous reports, we have synthesized a

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• task [25][26][27]. The electronic character of these intermediates, especially for boronic ester derivatives that allow coordination between oxygen atoms and the metal counterion, complicates predictable stereochemical outcome. Developing strategies to harness the exceptional nature of these carbanions

• lithium derivatives. Reactivity of α-boryl lithium intermediates 5 possessing alkyl substituents at the allylic position. Effect of the nature of the substituent R3 on the diastereoselectivity. Mechanistic hypothesis to rationalize the diastereoselectivity. Supporting Information Supporting Information

Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity

• Daria A. Burmistrova,
• Vasiliy A. Fokin,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Maxim V. Arsenyev,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65

• corresponding thioether 1 (AE = 2.45), both containing an isopropyl substituent. However, these AE values exceeded that of 3,5-DTBC, indicating enhanced neutralizing activity of the sulfur-containing derivatives. The ABTS assay is one of the most widely used methods for assessing the antioxidant capacity of

• values observed for compounds bearing isopropyl and tert-butyl substituents. Notably, sulfoxide 1a (isopropyl) showed enhanced antiradical activity compared to its thioether precursor, while for most other derivatives the activity decreased upon oxidation of sulfur. The combination of a primary

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• carbonyl group with a γ-lactam system, which enables participation in a wide range of nucleophilic additions, condensations, and cyclizations [7]. As a result, isatin has proven to be a particularly powerful synthon for the construction of 2-oxindole derivatives, including a large variety of spiro-fused

• , multicomponent systems combining isatin derivatives with diamines have been reported to furnish bis-spirocyclic architectures like 21 without detectable formation of the corresponding diimines 22 [20] (Scheme 3). Collectively, these precedents demonstrate that condensations of isatin with bifunctional nitrogen

• geometrical isomers (E/E, E/Z, Z/Z). These spectroscopic data are in agreement with those of previously described diiminoisatin derivatives [21]. When the reaction was carried out with an excess of ethylenediamine, a completely different product was obtained (Scheme 4b). Refluxing an ethanol solution of

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• with ketones resulted in unique di(pyridin-2-yl)methylene)-9H-diazafluorenes being electron-deficient ligands and functional materials. Keywords: acidic conditions; diazafluorene; diazafluorenylidene; Knoevenagel condensation; protonation; Introduction Diazafluorenylidene derivatives were reported to

• for their synthesis involves coupling reactions of diazafluoren-9-one [4][6][7] or diazafluoren-9-diazomethane [17][18] with thiones yielding the products in moderate yields (20–70%). However, these routes require the preliminary synthesis of malodorous thiones and diazomethane derivatives from the

• malononitrile or acetonitrile derivatives [14][19][20]. However, the use of diazafluorenes as the methylene component in condensation reactions remains underexplored. These reactions can be carried out under basic [13][21], acidic [3][5] or Lewis acid catalysis [15][22], but the corresponding literature

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• contribute to process chemistry for the synthesis of (E)-1,2-dibromo-1,2-diphenylethylene and their derivatives. Further synthetic investigations are currently underway in our laboratory. Experimental The experimental procedures and characterization data (Table 1, entry 1). The glass flask was dried and

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• a very useful tool to tune the thermal and optical properties, light-induced switching in particular. Monohalogen derivatives exhibited up to 93% E → Z photoconversion efficiency in solution, whereas the efficiency of dihalogen analogues is lower by 20%, which is ascribed to their nonplanar

• 1a vs 1b, 1c vs 1d; except for the bromine derivatives 1e and 1f where Ti is almost equal). The most pronounced difference was recorded for the chloro-substituted pair 1c and 1d (ΔTi = 41 °C). Electrochemistry The electrochemical behavior of azo-compounds 1a–f was investigated in 1,2-dichloroethane

• reverse reduction of the chemically modified oxidized form was recorded as a broad peak at significant undervoltage, especially for derivatives 1a–b and 1d–e. The electrochemical data suggest that the first oxidation and the first reduction processes are associated with different parts of the molecule

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• , and to support a balanced gut microbiota [7]. In view of this pleiotropic role, FXR activation has emerged as a well-established pharmacological target for MASH [8]. Consequently, a diverse range of FXR agonists – categorized as bile acid derivatives, non-bile-acid steroidal agonists, non-steroidal

• FXR agonist, served as the lead compound for a series of derivatives, such as cilofexor (GS-9674). Unfortunately, these agonists have failed in clinical trials because of side effects such as itching or a failure to meet primary endpoints. Despite the failure of several FXR agonists to achieve the

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• ]pyridine-2-carbaldehydes is reported. A Groebke–Blackburn–Bienaymé reaction between 2-aminopyridine derivatives, cyclohexyl isocyanide and glyoxylic acid in the presence of methanol and an acid catalyst gave the 2-ester derivatives that were reduced to give the corresponding alcohols. Mild Kornblum

• -chloroaniline. Alternative oxidation conditions such as PCC, IBX or T. versicolor laccase applied to the alcohols led only to oxidative ring-opening to give oxalamide derivatives, with no aldehyde being isolated. Keywords: 3-aminoimidazo[1,2-a]pyridine-2-carbaldehydes; Groebke–Blackburn–Bienaymé reaction

• found to act on targets in the central nervous system. For example, zolpidem (1) is used for the treatment of sleeping disorders, while alpidem (2), now discontinued due to safety concerns, was used for the treatment of anxiety (Figure 1). Other derivatives are currently under investigation for their

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• matter of current interest. For example, derivatives of teasterone (3), compounds 4–11, and castasterone, compounds 12–14, with benzoyl function at C-22 (Figure 2) have been synthesized, and their bioactivities have been evaluated by BSIB, RLIT, and inhibition of root and hypocotyl elongation in A

• in Table 2. The data indicate that derivatives with a OH group at C-3 (TE analogs) are much more active than derivatives with a carbonyl group in this position (3-DT analogs). However, the addition of another OH group at C-2 (CAT analogs) increases the activity of analogs substituted with p-methyl

• . thaliana seedlings. In the former test the best biological effects were observed for the analogs with 2α,3α-dihydroxy function (castasterone derivatives) as compared to those obtained for analogs with 3β-hydroxy (teasterone derivatives) and 3-carbonyl function. This result confirms that the best activity

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

• derivatives with multiple chiral centers under high regio- and stereocontrol. Currently, strategies using azomethine ylides based on imino esters or α-amino acids with a variety of cyclic and acyclic carbonyl compounds dominate. Enantioselective (3 + 2) cycloaddition reactions of azomethine ylides obtained

• ]. The use of azomethine ylides as dipoles is necessary for the synthesis of pyrrolidine systems, which are often found in natural products and are important structural fragments of pharmaceuticals [5]. This method is also used to obtain pyrrolizidine derivatives, which are the structural basis of

• -pyrrolizidine derivatives obtained from isatin, various α-amino acids and dipolarophiles is considered. This structural fragment plays an important role in biological processes, exhibiting antitumor activity, anti-HIV activity, anti-inflammatory, and, in some cases, analgesic effects. A 2016 review addressed

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• approved by the FDA are derived from natural products, their derivatives, or synthetic mimetics inspired by natural compounds [5]. The traditional knowledge of native plants for medicinal purposes is invaluable, and there are ongoing investigations by many research groups from around the world that aim to

• Eremophila-derived specialized metabolites or semisynthetic derivatives has the potential to impact biodiscovery research. In this study, we investigated the chemistry of the seeds of Eremophila maculata for the first time. Seeds from the Eremophila genus have rarely been chemically investigated due to

• uniquely abundant plant part afforded two known phytochemicals, (+)-salicifoliol (1) [15][16] and (+)-pinoresinol (2) [17]. The abundant natural product 2 was used as a chemical scaffold for semisynthetic studies. At the same time, all derivatives were fully characterized utilizing spectroscopic and

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• allylic position C13 being oxidized, a second allylic oxidation would possibly occur at the desired C5 position. However, when compound 8, as well as its acetyl ester (Ac) and tert-butyldimethylsilyl ether (TBS) derivatives, were subjected to several metal-mediated allylic oxidation conditions, either no

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• structure by a heteroatom (oxygen or nitrogen) in donor–acceptor, push–pull NBD derivatives are reported. In a computational study, Pawar and co-workers [7] further expanded the NBD structure by elongating the unsaturated bridge with different heteroatoms or functional groups. Azobenzenes, interconverting

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• more expensive compared to cyanoarene derivatives (Table S2, Supporting Information File 1). Considering the absorbance spectrum of 3DPAFIPN [29], violet (400 nm) and blue (450 nm) LEDs were evaluated as alternative light sources, resulting in increased yields of 50% and 54%, respectively (Table 1

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• primarily anthracene derivatives and benzyl C–H bonds, suggesting potential systematic errors in QM computations or experimental measurements. Radical and cation stabilities generally follow the trend: tertiary > secondary > primary methyl carbon stability. Our study also explores the correlation between

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• sulfonyl or sulfinyl derivatives. Biological evaluation revealed that several compounds, especially 3-nitro-5-sulfonyl- and 5-sulfinylisoxazoles, exhibit potent antimicrobial activity against Gram-positive bacteria, fungi, and notably low MICs comparable to those of standard drugs. The mechanism of action

• studies indicate that these compounds induce the bacterial SOS response without inhibiting DNA synthesis-related enzymes such as DNA polymerase I, DNA gyrase, or topoisomerases I and IV, suggesting activation via bacterial reductases. These findings highlight the potential of these isoxazole derivatives

• promising compounds with a wide spectrum of biological activity [1][2][3][4][5]. The attractiveness of isoxazole derivatives for medicinal chemistry is determined by high-affinity binding to many targets, low toxicity of isoxazole-containing compounds and the use of the isoxazole ring as a bioisoster of the

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• , that is the asymmetric metathesis dimerization (AMD; Scheme 1), was developed by our group during 2022–23 [30][31]. In the previous reports, racemic planar-chiral vinylferrocene [30] or vinylphosphaferrocene derivatives [31] were employed as substrates for the AMD process. In the presence of an

• )/kinetic resolution (KR) of racemic planar-chiral vinylcymantrene derivatives rac-1a–c The vinylcymantrene substrates, rac-1, prepared as above are planar-chiral due to the presence of an unsymmetrically substituted η5-(1-R-2-vinylcyclopentadienyl ligand (R = Br, Me, or I). The racemic substrates were