Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• conversion of the starting imine within 3 hours at rt and in 5 hours at −20 °C. Decrease of the temperature increases the enantiomeric purity of the product (from 27% ee up to 52% ee) (Table 1, entries 1–3). The corresponding H-analogue of catalyst A was less selective (18% ee) (Table 1, entries 4 and 5

• ). This suggests that possibly the halogen bond plays a role in the emergence of the stereoselectivity of the reaction. The reaction with the similar quinidine derivative with reduced double bond (catalyst B) was slower and less selective affording the opposite enantiomer in low enantiomeric purity (14

• % ee, Table 1, entry 6). Aminoindane-based catalysts C and D were inefficient and stereomeric purity of the products were not determined (Table 1, entries 7 and 8). The next group of catalysts consists of amino acid derivatives. The most selective was tert-leucine-based catalyst E affording the Mannich

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• 10.3762/bjoc.22.6 Abstract Three indan-2-one-based donor–π–acceptor–π–donor type dyes with symmetric donor groups were synthesized and characterized to study their nonlinear optical (NLO) properties and their potential use in the rapid and selective determination of cyanide. The designed structures

• using the EFISH method, where μβ values were found between 300 × 10−48 esu and 1740 × 10−48 esu and the highest value observed was with 2b. Dyes also showed chemosensor properties for the selective detection of cyanide with colorimetric and optical responses in both organic and aqueous media. The

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• limitation requires the design of catalysts that achieve precise electronic complementarity, enabling selective activation across a broad spectrum of aromatic compounds (Scheme 2) [32]. From the standpoint of scalable synthesis, catalyst cost is a major bottleneck in aromatic hydrogenation. Most state-of-the

• center and complicate catalysis. Consequently, designing cost-effective catalytic systems with enhanced efficiency, particularly for the selective hydrogenation of complex substrates, remains an essential direction for future research [33]. Hydrogenation of arenes has rapidly evolved from a specialized

• heterocycle part: Quinoline, one of the most accessible heteroaromatic feedstocks from natural and commercial sources, has long attracted interest in both synthetic and medicinal chemistry. A central challenge, however, is the selective catalytic hydrogenation of quinolines to the synthetically valuable

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• iodide 10n failed to give the desired products. In substrate 10o containing both iodide and bromide, selective activation of the alkyl iodide was observed, affording the coupled product in 96% yield. Furthermore, the reaction proceeded smoothly in the presence of alcohols 10p–q and carboxylic acid 10r

• range of α-fluorocarbonyl substrates and olefins (Scheme 9B). In 2025, Ota and Yamaguchi et al. reported a zirconocene-mediated selective cleavage of C–O bonds (Scheme 10A) [35]. The authors had previously demonstrated regioselective ring-opening reactions of epoxides and oxetanes by exploiting the

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• unavailability of other stable cycloheptatrienyl anions until recently, its derivatives were not expected to show high selectivity in reactions. Herein, we present the first examples of selective reactions of low-symmetry hexa(methoxycarbonyl)cycloheptatrienyl anion 2 [20] towards electrophiles. Additionally

• reported [31] halogenations of anion 1 only afforded the corresponding octasubstituted cycloheptatriene derivatives. The reactions of 2 with alkyl halides were selective in terms of the initial reaction – the i-substitution was never observed. However, the alkylation reactions were even more intricate than

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• demonstrated that aromatic alkynes can undergo hydrochlorination with good selectivity for the mono-addition when a nitromethane/acetic acid solvent mixture is employed (Scheme 27) [96]. In contrast, selective monohydrochlorination is commonly observed for alkynes bearing coordinating substituents such as

• two decades, considerable efforts have been devoted to the selective monohydrochlorination of alkynes, particularly through the use of transition-metal catalysis. Comprehensive reviews by Lu [40] and Nishiwaki [41] have extensively covered these advances. We also want to briefly mention the work on

• electrophiles A wide range of alkenylmetal species has been employed for the synthesis of alkenyl chlorides via reaction with chlorine electrophiles (Scheme 29). In a study from 1978, Zweifel demonstrated that 1,1-silyl(aluminum)alkenyl intermediates (e.g., 167) undergo highly selective chlorination at the

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• via methylation of a dianionic intermediate, proved unsuitable due to competing overalkylation and the necessity of sub-zero temperatures. In contrast, a transient protecting group approach enabled selective methylation under mild conditions. This culminated in a scalable, operationally simple one-pot

• ), selective methylation of maltol (2) would represent the most direct access to ethylmaltol (1). Herein, we disclose an operationally simple, one-pot methylation procedure to access ethylmaltol (1) from maltol (2, Scheme 1c). Results and Discussion Inspired by the selective γ-alkylation of dianions of β-keto

• esters [25], we initially envisioned the formation of dianion I from maltol (2), which should undergo selective C-methylation with methyl iodide to furnish ethylmaltol (1) (Table 1). Typical deprotonation conditions employed for β-keto esters, i.e., sequential treatment of maltol (2) with equimolar

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• applications in organic synthesis as precursors for free radicals in selective transformations [5][6][7][8][9][10][11] and polymerization initiators [12], energetic materials [13][14][15], NO donors [16][17], and organic light-emitting diodes (OLEDs) [18]. Despite the wide diversity of their applications

• , structures, and redox properties, effective synthetic strategies for the construction of N–N and N–O systems remain markedly underdeveloped. Unlike traditional methods for constructing C–C and C–Het bonds, the number of methods for selective N–N [1][5][19][20][21][22][23][24][25][26][27][28][29] and N–O [30

• and N–O bond formation. However, it also represents a highly efficient and valuable strategy due to the synthetic availability of starting materials. Therefore, the development of new methods for direct selective N–N and N–O coupling remains an important goal in synthetic chemistry. To date

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• butenolide moiety, selective α-methylation, formation of a lactam, reduction of the former to an amine, and installation of two different protecting groups. Aryl bromide 53 (fragment B) was then ready for coupling. Lithium–halogen exchange in fragment B 53 and subsequent 1,2-addition to fragment A 47

• of ring D and spirocyclization were to be executed. The next three steps included a Birch reduction, selective hydrogenation with PtO2, and protecting group installation to give 56 with the double bond at C13–C17, which was crucial for the following spirocyclization. This double bond was epoxidized

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• hand, we first tried the synthesis of rhodexin A through direct glycosylation of 2 by the ʟ-rhamnose donor 2,3,4-tri-O-benzoyl-α-ʟ-rhamnopyranosyl trichloroacetimidate (14). However, the selective glycosylation at the C3-hydroxy group of 2 was a formidable challenge since competitive glycosylations of

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• report a new material, SG-NHCO-BU1, in which the BU1 macrocycle is covalently grafted onto the surface of silica gel. We demonstrate that this hybrid material can be used for the selective dicyanoaurate(I) sorption from water. Moreover, it is shown that unlike SG-BnBU, SG-NHCO-BU1 exhibits good stability

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• cycloalkanone scaffolds with potential applications in pharmaceutical and materials sciences (Scheme 12) [62]. Sumida, Ohmiya, and co-workers recently developed an NHC-and organic photoredox-catalyzed meta-selective Friedel–Crafts type acylation of electron-rich aromatic compounds 31. The described catalytic

• catalyst. The anticipated meta-acylation product 32 was achieved through highly selective C(sp3)–C(sp3)-radical–radical cross-coupling between the cyclohexadienyl radical C and the benzyl radical species F, formed via single-electron reduction. This photochemical method overturns the traditional ortho and

• /photoredox catalyzed borylacylation of alkenes. NHC-catalyzed oxidative functionalization of cinnamaldehyde. NHC/photocatalyzed oxidative Smiles rearrangement. NHC-catalyzed synthesis of cyclohexanones through photocatalyzed annulation. Dual organocatalyzed meta-selective acylation of electron-rich arenes

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• , which was subsequently subjected to a one-pot desilylation to afford 24. Reduction of both the ester and ketone functionalities in 24, followed by selective protection of the primary alcohol and re-oxidation of the secondary alcohol to ketone, furnished compound 25 in three steps. The ketone in 25 was

• % yield (63% brsm) or 50% yield after four cycles with recovery of starting material. Selective epoxidation of the isopropenyl group with m-CPBA delivered cyclization precursor 45 as an inseparable mixture of diastereomers (dr = 1:2.1). A Cp2TiCl-mediated cyclization of 45 constructed the tricyclo

• rearrangement only under Lewis acidic conditions to furnish 47. Selective TES deprotection with HF afforded Rychnovsky’s intermediate 29. (−)-Illisimonin A was obtained in 13% yield over the same 4-step sequence as reported by Rychnovsky’s group. An alternative 4-step endgame starting from 47 was also developed

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• ryanodine (1) from ryanodol (4) – had long eluded chemists. The primary challenge involved the selective installation of the bulky pyrrole unit onto the sterically congested C3 secondary hydroxy group within a polyfunctionalized, polyhydroxylated framework. In 2016, building upon prior work, the Inoue group

• introduction of diverse substituents at the C2 position and precise modulation of oxidation states at other sites, including C3. The synthesis of 3-epi-ryanodol (5) commenced with compound 44. After the protection of the C10 secondary hydroxy group, a sterically controlled, face-selective reduction of the C3

• of (+)-ryanodol (4) in just 15 steps, highlighting the Pauson–Khand cyclization and a selenium dioxide-mediated selective oxidation as key transformations [48] (Scheme 7). To construct the multi-substituted five-membered ring in the target molecule, the authors strategically employed the Pauson–Khand

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• followed by reaction with CH(OMe)3 afforded acetal 17, which was then subjected to a CH2Cl2 solution of TMSOTf and iPr2NEt. A mixture of enol methyl ethers 18 were thus produced by an elimination reaction. Eventually, a site-selective bromination of the double bond over the electron-rich benzene rings with

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• confirmed by comparison with the calix[4]arene precursor (1) lacking these functional units. The selective antiproliferative profile of compound 3 highlights its potential as a lead anticancer agent. Moreover, compound 3 holds promise for further development in combination multidrug therapy due to the

• mechanisms including elevation of reactive oxygen species (ROS) or interference with redox homeostasis, and inhibition of kinase or topoisomerase activities essential for cancer cell proliferation. The selective activity of thiouronium salts against cancer cells compared to non-malignant cells can be related

• discriminate between normal and cancer cells, as demonstrated by the calculated SI of 0.47. The high SI value by compound 3 evidenced the isothiouronium moieties retain the selective cytotoxicity towards cancer cells also when tethered to the calixarene scaffold. Since the long alkyl chains in compound 3 could

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• acid (RNA) impacts many biological processes; however, the complexities of its many roles are not completely understood. Therefore, designing tools for molecular recognition is of paramount importance. Peptide nucleic acids (PNA) show promise as a tool for selective recognition of double helical

• than 10 times stronger to RNA than to DNA [19]. Since the seminal report, much work has focused on exploring synthetic nucleobases in efforts to develop tools for sequence selective recognition of any RNA [13]. Figure 1 shows several of the most common monocyclic nucleobases used for each of the four

• monomer. We reported a similar result for 5-triazolyluracil [28]. However, despite the development of pyrimidine-recognizing bases (P, P9, E, etc.), the sequence selective recognition of any double helical region of RNA remains an elusive problem owing to the difficulties in pyrimidine recognition via a

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• valuable platform for the selective functionalization of carbazoles, offering potential applications in optoelectronics, functional organic materials, and related areas while contributing to the advancement of C–H activation methodologies. Keywords: C–H activation; carbazole; catalysis; nitration

• nitration of carbazole is highly desirable [68][69]. In this context, we envisioned utilizing a directing group-assisted regioselective C–H activation strategy to achieve the C1-selective nitration of carbazole. Through our efforts, we identified a palladium-catalyzed reaction system for C1 nitration of

• ). Plausible catalytic cycle. (a) Representative examples of bioactive nitrocarbazoles. (b) Traditional electrophilic aromatic substitution approach for the nitration of carbazole. (c) Present work: palladium-catalyzed directed C1-selective nitration reaction. Effect of directing groups on the nitration of the

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• available (+)-sclareolide (101) as starting compound, from which key alcohol 102 was synthesized in 7 steps. Selective mesylation of the secondary alcohol in 102 followed by semipinacol rearrangement catalyzed by t-BuOK afforded diketone 104 as a pair of epimers at C12 in a 1:1 ratio, with 70% overall yield

• -dihydronaphthalenes. Silva et al. have also developed an effective method for the stereoselective oxidation of tetralone derivatives using chiral hypervalent iodine reagents [61][62]. Hypervalent iodine compounds are widely used in organic synthesis as selective oxidants and enantiomerically pure reagents. In terms

• 2012, Lin and co-workers [69] isolated the membrane diterpenoid (−)-134 from the marine soft coral Sinularia pavida. The study showed that (−)-134 exhibits highly selective inhibition against the human promyelocytic leukemia cell line HL-60 with an IC50 of 2.7 μg/mL. Structurally, (−)-134 contains a

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• moiety have been isolated and demonstrate potent bioactivities [7] (Figure 1). For example, lactacystin (1) which was isolated by Ōmura and co-workers [8][9], is a potent and selective proteasome inhibitor; its active form is the synthetic precursor omuralide (2) [10][11]. Similarly, salinosporamide (3

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• selective recognition. Balancing binding affinity and selectivity through precise conformational engineering remains a critical challenge [11]. Previous studies, such as those by Tian et al. [12], demonstrated selective binding in chiral assemblies via crown ether chain-length modulation. The dynamic

• by enabling dynamic host–guest complementarity. Such insights are critical for designing adaptive receptors for applications like environmental sensing or selective ion extraction. Conclusion In summary, two carbazole-based macrocyclic structural analogs (PBG and WDG) were synthesized via a

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• form selective hydrogen bonds between the carbonyl oxygen of the fumaramide unit and the N–H groups of benzylic amide rings. Upon isomerization to the cis isomer, the hydrogen-bonding interactions are weakened, enabling the macrocycle to migrate to a second recognition station [61]. Despite their

• selective detection of sulfite for potential biological applications. Furthermore, the same group reported a photoswitchable [2]rotaxane containing a spiropyran stopper and a macrocycle armed with tetraphenylethylene for photopatterning applications (Figure 11) [20]. The macrocycle has been shown to shuttle

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

• receptor (GPCR) X2 (MrgprX2), which is highly expressed in neurons and functions as a modulator of pain. Complanadine A serves as a selective agonist of MrgprX2. Structurally, complanadine A is an unsymmetrical dimer of the tetracyclic lycodine (5) via a C2–C3’ linkage [9][10]. Complanadine B is a mono

• , followed by acetylation of the resulting propargylic alcohol afforded 17 which was further advanced to 18 via copper-catalyzed selective displacement of the propargyl acetate with benzylamine and hydrolysis of the primary acetate. The primary alcohol of 18 was activated with PPh3/CCl4, triggering an

• synthetic route enabled Siegel and co-workers to determine the first biological target of complanadine A. Screening against a panel of cell surface GPCRs revealed that complanadine A acts as a selective agonist of MrgprX2, while the monomer lycodine showed no significant activity towards this target. This

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

• favor Norrish–Yang cyclization over the competing unproductive Norrish type II fragmentation pathway; (2) the long excitation wavelength of 1,2-diketones (λmax ≈ 450 nm) enables their selective activation in the presence of other photochemically excitable groups [5][6]. Furthermore, the resulting α

• C5–C6 bond) was subjected to Norrish–Yang cyclization conditions (Scheme 5b), the two methyl groups at C4 initially underwent non-selective 1,5-HAT, resulting in a loss of both regio- and stereoselectivity. In both cases, the functional groups on the ring E likely exert a significant influence on the

• (44) would trigger a quinone-based Norrish–Yang cyclization, enabling divergent synthesis of these meroterpenoids (or their core structures). In Yang's divergent total synthesis, Wieland–Miescher ketone (18) served as the starting material. Selective acetalization of the non-conjugated ketone in 18

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

• found that the water-soluble naphthalene-walled glycoluril dimer G2M2 (Figure 1) – with its roughly co-planar aromatic walls – is selective for planar aromatic cations as guests [38]. In order the complement the tricyclic ring system present in the panel of dyes (Figure 2), we envisioned the use of even