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

• among chemistry and chemical industry community [1][2][3][4][5][6][7][8][9]. Given this longstanding significance, the development of controlled reduction strategies has diversified to accommodate the distinct reactivity and selectivity. Representatively, complete hydrogenation of alkynes or alkenes is

• transition-metal catalysis [13][14][15][16][17][18] that enables cost-effective hydrogenation reactivity and electroorganic synthetic strategies [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] that employ externally applied potentials to achieve bond reduction with operational

• -based systems [38][39]. In sharp contrast, electroorganic synthesis provides a fundamentally distinct mode of reactivity compared to conventional thermochemical approaches, in which electric current serves as the terminal reductant, thereby enabling unconventional mechanistic pathways for alkyne

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

• % aqueous ethanol are virtually indistinguishable from those reported for pure aqueous solution [12][21]. Notably, compound 7a was reduced by glutathione alone in the absence of ascorbate, precluding accurate second-order rate determination under standard conditions. This enhanced reactivity likely stems

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

• aza-heterocycles often exhibit attenuated nucleophilicity, distinct acidity profiles, and potential coordination to metal centers, all of which can significantly influence catalytic reactivity and selectivity [20]. Therefore, the development of catalytic systems that can accommodate the unique

• )aromatic N–H nucleophiles. Notably, ligand design has emerged as a powerful tool for tuning the reactivity and selectivity, including control over Markovnikov vs anti-Markovnikov addition and enantioselective induction in selected cases. These developments collectively underscore the unique adaptability of

• β-amino nitrile motifs, which are commonly found in biologically active molecules. However, the relatively low nucleophilicity of aromatic amines and N-heteroaromatic substrates often limits their reactivity in conjugate addition reactions. To overcome this limitation, transition metal catalysis has

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

• substituent reduces substrate reactivity, thereby diminishing the efficiency of the key ring-closing step and often resulting in low overall yields [45]. Moreover, these methods commonly rely on strongly basic conditions, particularly the use of highly reactive tert-butyllithium, which further reduces their

• improved strategy based on brominated precursors [45]. Owing to the weaker electron-withdrawing effect of bromine relative to carboxy groups, these precursors exhibit higher reactivity and enable the construction of brominated SiR scaffolds in improved yields (60–70%) under milder conditions. Subsequent Pd

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

• reported [44][45][46][47][48][49][50][51][52][53][54], although the reaction mechanism with π-deficient N-heteroaromatics has not been elucidated (Scheme 2b). It is therefore valuable to investigate the differences in reactivity between C–H and N–H for intermolecular arylation in the presence of transition

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

• essentially binary synthetic building blocks consisting of a highly strained small ring and an active functional group that are capable of reacting in domino or orthogonal modes. This dual reactivity allows their use in the syntheses of monocyclic heterocycles [11][12][13][14], fused heterocycles [15][16][17

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

• delocalization leads to the formation of a partial π C–B bond (Scheme 1) [1][2], which provides a unique stabilization to the carbanionic center and affects its reactivity towards electrophiles. In recent years, α-boryl carbanions have attracted significant attention as highly versatile intermediates capable of

• regioselectivity. The use of various electrophiles enabled the synthesis of acyclic boronic esters featuring vicinal tri- and tetrasubstituted stereocenters. Cyclopropylmethyl iodide starting materials. Synthesis and reactivity of α-boryl lithium species. Diastereodivergent electrophilic trapping of α-boryl

• 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

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• While numerous native-sequence protein-modification tools exist with many being site-specific, few can fulfil all the aforementioned criteria simultaneously. Cysteine modification is among the most effective strategies due to the high reactivity of the thiolate, enabling selective chemical

• has become a cornerstone of biological research and therapeutic development, with applications including in vitro systems, live cells and animal models. The earliest form of affinity-guided labelling traces back to mechanism-based inhibitors, which exploit heightened reactivity of active-site residues

• -sequence protease substrates through site-specific hydrolysis and isopeptide-bond formation (Scheme 6) [47]. Labelling residues on protein surfaces is noticeably more challenging due to a lack of residues with heightened reactivity. Substantial progress has been made to address this issue, with current

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• gold(III) complexes has more recently become a focus of interest. Although often underestimated or not considered, the ligand trans-influence is a crucial factor in determining the reactivity of gold(III) compounds; it modifies not only bond polarisation, dissociation energies and thermal stability but

• and reactivity in catalytic reactions [11][12][13][14][15][16][17][18][19]. There is however one important aspect of gold chemistry that is often under-appreciated: the strong control of reactions by the influence of a given ligand on another ligand in trans position, known as the trans-influence

• complexes and their role in catalytic applications [20]. While not aiming to be comprehensive, this Perspective seeks to highlight pertinent examples demonstrating the importance of the ligand trans-influence in gold chemistry, with special emphasis on the reactivity of gold(III), and its influence on gold

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

• states provides a powerful way to control organic molecules. Through the controlled conversion of thioethers to sulfoxides and sulfones [21], it is possible to tune their reactivity and biological properties. Indeed, compounds of this type possess pronounced neuroprotective properties [12][13][14

• obtained in the ABTS-test were lower than those determined in the DPPH assay, which is due to the different reactivity of the two radicals. The most pronounced antioxidant activity (7.2–9.3 µM) was exhibited by compounds 1, 1a, 2, and 2a, bearing an isopropyl or tert-butyl substituent at the thioether

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• . Key synthetic challenges including the stereoselective construction of the 1,2-cis glycosidic linkage on the galacturonic acid core and the inherently low reactivity of elongated oligosaccharide intermediates were addressed employing orthogonally protected building blocks. The resulting library of

• assembly and subsequent functionalization of long oligosaccharide chains are hampered by their intrinsically low reactivity [29]. Overcoming these challenges relying on a linear strategy employing four key building blocks 1–4, we describe the first chemical synthesis of the hexasaccharide repeating unit

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

• , IACT-CSIC. Avda. de las Palmeras 4, 18100 Armilla (Granada), Spain 10.3762/bjoc.22.63 Abstract The reactivity of isatin toward ethylenediamine displays an unexpected stoichiometric divergence, affording either the anticipated diiminoisatin or a previously unreported pentacyclic bis-spirooxindole. A 2

• approaches [2][3][4][5]. In this context, comprehensive medicinal chemistry studies consistently highlight the prominence of isatin-derived frameworks among bioactive and anticancer agents [6]. The remarkable reactivity of the isatin scaffold arises from its dual functionality, combining an electrophilic C-3

• . In this context, we turned our attention to the reaction of isatin with unsubstituted ethylenediamine. Although analogy with related diamines would suggest preferential diiminoisatin formation, our results reveal a pronounced divergence in reactivity under different conditions, prompting a detailed

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

• diazafluorenes’ nature and solvent influence on the mechanism and reactivity. We also identified conditions allowing the preparation of both 4,5- and 1,8-diazafluorenylidenes in yields up to 85% minimizing complicated synthetic or experimental workup procedures. Additionally, the condensation of diazafluorenes

• assumed that 4,5- and 1,8-diazafluorenes may have different reactivity in the Knoevenagel condensation and the development of efficient and convenient synthetic routes to diazafluorenylidenes is of considerable importance. Here, we systematically studied the Knoevenagel condensation of both 4,5- and 1,8

• -diazafluorenes with aromatic aldehydes and evaluated the influence of the diazafluorene nature and solvent on the reaction mechanisms and reactivity. The reactivity of diazafluorenes under basic conditions was demonstrated to be improved in protic solvents due to solvation of ion pairs by these solvents. We

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• the reactivity of other readily available sulfinate nucleophiles using competition and exchange experiments. Keywords: diastereoselectivity; Rongalite; sulfones; Introduction Sulfonyl groups are widespread in licensed drugs [1]. New methods for the incorporation of sulfonyl groups into organic

• used as a bleaching agent in the dyeing industry for more than a century [5][6]. Over the last 10 years particularly, it has begun to join the toolbox of reagents in organic synthesis, and shows diverse reactivity. It has been employed in reductions, radical processes and as a reagent for C1 transfer

• , few reports documented this behavior for Rongalite (Scheme 1). This may have been due to its known reactivity as a conjugate reductant [17][20]. We recently published a preliminary report on the reaction of Rongalite with dienones leading to cyclic sulfones (Scheme 1) [21]. We now describe our efforts

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

• enantioselectivity was observed. In a similar study, Wang et al. reported the CuI/TF-BiphamPhos (L3) complex, a new and highly efficient catalyst for the asymmetric 1,3-dipolar cycloaddition reaction [38]. The authors noted excellent reactivity, selectivity, and a wide range of structural variants for various

• imidazoles 18 catalyzed by Cu(I)/phosphine L10, which resulted in the formation of chiral pyrrolidines 19 and 20 with high diastereoselectivity (Scheme 11). The authors attribute the reactivity patterns observed in imino esters reactions, including regioselectivity variations, by differences in electron

• in the asymmetric (3 + 2) cycloaddition of iminoethers with various 2-alkylidenecyclopentanones [53] In 2025, Wang and co-workers carried out a cascade enantioconvergent reaction between aldimine esters 1 and low-reactivity allylic alcohols 30, which are activated by oxidative dehydrogenation to form

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

• reports on direct modifications of the casbene skeleton, we thus commenced our synthesis with probing the reactivity of 4 by screening a series of conditions for allylic oxidation (Table S2 in Supporting Information File 1). However, most of the conditions tested did not give satisfactory results, as

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

• the meta-isomer formed in noticeably higher proportion than the para-isomer. The introduction of a methyl substituent into the anisole framework significantly altered the reactivity, with a strong dependence on the relative position of the substituents. For the meta-substituted substrate, the yield of

• trifluoromethylated product was high (74% for 13), whereas the para-substituted analogue provided only 18% yield (14). To further investigate the influence of substituent position on substrate reactivity, reactions with dialkylanisoles were examined. For meta-methylanisoles bearing an additional methyl group at the

• , introduction of a third methyl substituent reduced the yield nearly threefold, affording only 33% of product 18. These observations suggest that the relative arrangement of electron-donating substituents exerts a greater influence on reactivity than their overall donating effect. Three isomers of

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• silicon compounds was observed in all reactions (see Supporting Information File 1, Figure S3). Noteworthy, by replacing formic acid with acetic acid only 1 equivalent of hydrogen was released. The different reactivity towards the dehydrogenative coupling of the silyl carboxylate species can be due to

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

• host of other reactivity predictors. Keywords: bond dissociation energy; hydricity; hydride affinity; hydride-transfer reactions; machine learning (ML); quantum chemistry (QM); Introduction Bond dissociation energies (BDEs) and pKa values for C–H bonds are often used to rationalise and predict the

• tertiary > secondary > primary reactivity pattern; it is thus not clear whether hydricities offer an advantage over BDEs. Furthermore, for reactions involving bulky catalysts and/or functional groups the regioselectivity will also be dictated by the steric accessibility of the C–H site (Figure 1). In this

• ). Many of these transformations are not formal hydride transfers; however, they commonly involve buildup of positive charge (e.g., via metal–carbene/nitrene insertion transition states, radical cations, or polar hydrogen atom transfer). Hydricity could therefore serve here as an empirical reactivity

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• often suffers from insufficient reactivity and conversion, even under harsh reaction conditions, such as high temperature and pressurized hydrogen, or when employing advanced technologies [8][9][11][12]. The selective hydrogenation of carbonyl moieties often needs to overcome the problem of

• 1.2 atm in this case (0.2 atm pressure loss). The yields of 1-phenetylalcohol (2a) and by-products 3a and 4a under these reaction conditions for each catalyst are summarized in Table 1. The commercially available catalysts (Pt/C, Pt/SiO2, Pt/Al2O3) and Pt/DMPSi‒Al2O3 showed poor to moderate reactivity

• , and the hydrogenation of the aromatic moiety proceeded as well to give by-products 3a and 4a (Table 1, entries 1‒4). Pt‒Au and Pt‒Ni bimetallic catalysts immobilized on DMPSi‒Al2O3 also showed moderate reactivity, accompanied by the formation of by-products (Table 1, entries 5 and 6). Interestingly

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• carboxylic acid derivatives (Scheme 2b) [43]. They revealed that ortho-alkoxy substitution on the benzene-derived alkyne markedly enhanced both reactivity and enantioselectivity, while incorporation of a naphthyl substituent into the diyne enabled access to remote biaxially chiral molecules. Subsequent

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• transformation. The phenyl selenolate is widely used in organoselenium chemistry as a source of selenium due to its high reactivity toward halogenated substrates and excellent chemical stability. The n-octyl selenolate is comparatively less explored but readily undergoes substitution reactions with halogenated

• energy gap, which are key parameters for understanding the compound's chemical reactivity and stability. In both compounds, the HOMO is mainly localised on the tert-butyl-substituted phenyl ring, while the LUMO is localised on the naphthalimide moiety. For both structures, the estimated energy gaps are

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• previous findings on the reactivity of 2-azidoethylated calix[4]arenes with arylacetylenes under CuAAC conditions [81], calixarene 35 bearing four 2-azidoethyl groups at the narrow rim was reacted with phenylacetylene under heating using CuI·P(OEt)3 as a catalyst (Scheme 7). In contrast to the synthesis of

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• electrochemical arenol activations reported by Waldvogel and co-workers [46]. Subsequent intramolecular dehydrative cyclization furnishes the desired oxaza[8]helicenes 5. The oxidation-potential gap between 3 and 4 and the reactivity of Int-I thus provides a handle to control chemo- and regioselectivity

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• . Collectively, the articles in this Thematic Issue should not be viewed as an exhaustive account of non-central chirality but rather as representative snapshots of an evolving landscape. They capture the current state of the field, where structure, reactivity, dynamics, and function increasingly intersect under