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

• reduction of unsaturated C–C bonds can be broadly classified according to whether the reaction proceeds through a discrete metal hydride (M–H) intermediate (Figure 2A) [49][50][51][52][53] or through a hydride-free pathway (Figure 2B). In the first category, electrochemical reduction/protonation sequences

• metal–alkenyl intermediate. In some cases, this organometallic species can further undergo chain walking, where iterative β-hydride elimination and reinsertion enable migration of the metal center along the carbon skeleton before product release, thereby allowing remote hydrogenation or positional

• selectivity [54][55][56]. The second mode within M–H chemistry is hydrogen-atom transfer (HAT), namely MHAT [38][57][58][59][60][61][62][63], in which the electrogenerated M–H intermediate behaves not as a classical two-electron hydride donor but as a one-electron H-atom donor. In such cases, reactivity is

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

• suitable ligands such as N-heterocyclic carbenes or electron-rich phosphines, the deprotonation of an N–H heteroaromatic can generate a copper–amido intermediate [32][33][34]. These species typically exhibit enhanced nucleophilicity and can engage alkenes via the direct nucleophilic addition of a copper

• –amido intermediate or aminocupration-type pathways, enabling efficient C–N bond formation under relatively mild conditions. Copper species may also operate in a Lewis acid-type capacity, where coordination to the alkene or copper-derived Brønsted acidity generated in situ increases alkene

• been widely explored. Among the various catalytic systems, copper catalysts have attracted particular attention owing to their ability to activate amine components by forming copper–amido species. In this activation mode, deprotonation of the N–H bond generates a Cu–N intermediate with enhanced

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

• HRMS (Figure S24) analysis identified this side product as the uncarboxylated rhodamine formed by lithium–halogen exchange followed by protonation. This byproduct likely arises from protonation of the aryllithium intermediate before efficient trapping by CO2, possibly due to trace moisture or other

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

• group in the C5 position, a similar substitution pattern was detected as for compound 3ad derived from 1-bromo-2-iodo-5-methylbenzene (2b). Additionally, during the coupling reaction carried out with 5-tert-butyl-1-bromo-2-iodobenzene, Int-1ad species was detected as a reaction intermediate, as

• . First, the activated palladium(0) catalyst is inserted into the carbon–iodine bond of the 1-bromo-2-iodoarene 2 via oxidative addition. The intermediate Int-2 then undergoes ligand exchange from iodine and phosphine to acetate and quinoline-2-carboxamide to generate intermediate Int-3. Then, through a

• concerted metalation-deprotonation (CMD) process, a carbon–palladium bond is formed to give the palladacycle intermediate Int-4. Next, reductive elimination between the quinoline and arene moieties forms the C–C bond to give intermediate Int-1 and regenerates the palladium(0) catalyst. Another oxidative

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

• with aromatic aldehydes does not result in the formation of an azirinyl-substituted β-hydroxy-α-diazocarbonyl compound, but is accompanied by a tandem intramolecular cyclization involving the hydroxy group and the C=N bond of the azirine to form a bicyclic intermediate, a 4-diazo-2-oxa-7-azabicyclo

• bicyclic intermediate 4. This acid-catalyzed transformation leads to 3-hydroxy-2-aroyl-1H-pyrroles 5 (Scheme 1). To the best of our knowledge, only few examples of such compounds have been so far reported [23][24]. Results and Discussion A test reaction of 2-(2-diazoacetyl)-3-phenyl-2H-azirine (1a, R = Ph

• ring. The intermediate (RR,RR)-B immediately yields a more stable conformer with the Ph group from benzaldehyde in the equatorial position (1RR,3RR,6RR)-Phe-C, but the equilibrium as a whole is shifted towards the most stable isomer (1RR,3SR,6RR)-Phe-C isomer. According to the calculation, the

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

• enhance the formation of transition state B. The highly diastereomic ratio of 6a in syn-form may be generated from transition state B. The formation of intermediate C is the rate-limiting step. When intermediate C is formed, the protonation happened rapidly to afford 6a in high enantioselectivity. The

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

• results suggest that the stereochemical outcome is independent of the initial configuration at C2 and is instead dictated by conformational preferences of the α-boryl lithium intermediate. A simplified steric model is proposed in which lithium coordination induces a pseudo-chelated structure that controls

• cleavage of the C1–C3 bond rather than the C1–C2 bond, provided direct access to α-boryl carbanion intermediate 1. Reaction of 1 with a range of electrophiles furnished tertiary pinacol boranes with a well-defined adjacent stereocenter in excellent diastereoselectivity (Scheme 1). Theoretical studies

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

• has enabled pyridinium aldoxime 21 (PyOx) incorporation into protein scaffolds (Scheme 7e) [64]. Acting as a catalytic centre for acyl cation transfer, PyOx reacts with a selected N-acyl-N-alkyl sulfonamide 15’ to generate a reactive ester intermediate. This strategy has successfully modified lysine

• , the enzyme cleaves the Thr–Gly peptide bond to form an acyl intermediate that is ligated to an incoming primary amine nucleophile, such as an N-terminal glycine or lysine ε-amine (Scheme 14a) [143]. Native proteins with an N-terminal glycine and sufficient flexibility can thus be directly modified by

• and glutamine (or other small primary amides) is another frequently used enzyme for bioconjugation. The primary amide in glutamine is converted into an acyl intermediate that is subsequently attacked by amine nucleophiles such as lysine ε-amines and glycine α-amines. Although MTG can modify Gln295 on

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

• ^C)AuH2] [50]. Goldberg’s complex 13, on the other hand, which is stabilised by two strongly donating P(t-Bu)2 moieties, is stable at room temperature and could be crystallographically characterised [53]. A gold hydride of type 12 has been postulated as an intermediate in the thermal decomposition of

• (C^C^N)Au–C(R)=C(R)H (Z-configuration), most probably via (C^C^N)AuH as intermediate [54]. Allenes are more reactive, and both (C^N^C)AuH 8a and [(P^N^C)AuH]+ 11 give allene-insertion products, by unspecified mechanisms [31][52]. This picture changed however when it was realised that (C^N^C)AuH

• deprotonation [29] of [(P^N^C)AuH]+ by water, to give a T-shaped Au(I) intermediate, (P^N^C)Au, capable of sequestering the alkyne. This in turn is attacked by another Au(III) hydride to complete the anti-addition process (Scheme 13) [69]. Ligand effects of C^N, C^P and P^N chelates Gold(III) complexes of C^N

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

• transformations of the sulfur-centered intermediate can lead to the corresponding sulfone via a disproportionation reaction or in the presence of traces of water [49]. In the case of compounds 2a and 5a, which bear a tertiary hydrocarbon substituent at the sulfinyl group (tert-butyl and adamantyl, respectively

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

• -throughput screening, a series of analogues including di-, tri-, tetra-, and pentasaccharides were synthesized (Scheme 3). We utilized the intermediate products from the assembly of the hexasaccharide repeating unit 20. The protecting groups of disaccharide 13 were removed by treatment with sodium methoxide

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

• interested in the selective synthesis of the E isomer of 1,2-dibromo-1,2-diphenylethylene, together with simple purification and separation toward process chemistry, because the compound is an attractive synthetic intermediate for further transformations. During the course of our studies, we have found that

• ). Poor selectivity as shown in entries 1 and 2 might be due to the stability of the intermediate. In the cases of Table 2, entries 3–6 residues such as MeO, F, Br and CN as the substituent at para position of the benzene ring in 1d–g, the selectivity of E and Z and the isolated yield of the E isomer

• can react with 1a to form intermediate A. A reacts with Br− to give E-2a. Another possibility is the reaction of NBS and FeBr3 gives coordinated intermediate B, which can react with 1a to give A, leading to the formation of E-2a [21][22]. Both pathways may be mixed together. One reason why E and Z

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

• MASH. Results and Discussion Chemistry The synthetic routes to the target compounds are outlined in Schemes 4–8. The synthesis of isoxazole intermediate 2 commenced with the condensation of commercially available benzaldehyde I with hydroxylamine to afford oxime intermediate II. Subsequent treatment of

• II with NCS, followed by cyclization with methyl 3-cyclopropyl-3-oxopropionate, furnished isoxazole IV. Reduction of IV with lithium aluminum hydride gave alcohol V, which was then brominated with phosphorus tribromide to yield the desired isoxazole intermediate 2 in five steps (Scheme 4) [31]. The

• preparation of triazole intermediates IXa–d is shown in Scheme 5. Firstly, compound VI was reacted with hydrazine hydrate in methanol to obtain hydrazide VII which was mixed with DMF/DMA and heated to provide intermediate VIII. The obtained VIII was not purified and directly reacted with different amines to

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

• binding energies obtained from a docking study. In this way, it is intended to assess the effect of chemical structure on the initial and one intermediate step, and on the final plant response. Our results show that the binding of BR analogs to the active site, which initiate the signaling process, and

• . thaliana seedlings [28][29]. The obtained results indicate that compounds 10 and 11 are the most active of teasterone analogs [28], whereas fluorinated castasterone analogs 13 and 14 with a fluoro substituent in the ortho- and para-positions, show interesting activities at intermediate concentrations [29

• data suggest that the initial step of the signaling process and the subsequent dephosphorylation of BES1 depend on the structure of BRs analogs in the same way. In other words, the interaction between BRs analogs and the binding site determines the response of the plant and one intermediate step

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

• system 18. However, we did not obtain any of the desired product, with low conversion and a mixture of products, none of which were sulfone 18. The absence of cyclized product is likely due to the necessity of forming a bridgehead enol intermediate which violates Bredt’s rule [42]. A larger ring

• does not conclusively indicate beyond all doubt the lower nucleophilicity of Rongalite – it is still possible that loss of formaldehyde from an intermediate such as 28 (inset in scheme to Table 1) is rate-determining. We can, however, conclude that conjugate addition of p-toluenesulfinate is

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

• authors proposed a model for the intermediate complex in 1,3-dipolar cycloaddition reactions. This intermediate consists of an azomethine ylide coordinated to a Zn(II)-t-Bu-BOX catalyst and is an 18-electron complex with a tetrahedral arrangement of ligands around the zinc center. Excellent results for

• shielding of the Si-side of the chiral iminium intermediate by bulky aryl groups leads to a stereoselective endo approach of the 1,3-dipole to the sterically less hindered Re-side of the intermediate iminium cation (Scheme 26). In this context, it is worth noting a work published in 2011, in which the

• -alkylmaleimides 63, with the formation of cycloadducts 68. Next, without isolating the intermediate product 68, the resulting reaction mixture was used for the intramolecular (3 + 2) cycloaddition step with alkynes 69 and alkenes 70, which led to the formation of cycloadducts 71 and 72 with high

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

• purity (>95%). Semisynthetic analogues 3−5 are known compounds [25][26]. However, some of these compounds have not been fully characterized. Regarding compound 5, this molecule had previously been reported as an intermediate in the total synthesis of racemic pinoresinol [25]. Through a bromination

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

• Cichorium intybus, while multiple products were produced when the same compound was treated with acid or Hg(OAc)2, indicating (+)-hedycaryol might serve as the biosynthetic intermediate of compound 2 [37]. Terpene cyclase TwCS from Tripterygium wilfordii responsible for the biosynthesis of 2 was discovered

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• construction. The synthesis of the ATP-site binder began with the alkylation of commercially available methyl 3-aminobenzoate (3) using bromoacetyl bromide. Although initial purification via silica gel chromatography led to substantial product loss, isolation by simple aqueous workup afforded the intermediate

• 4 cleanly and in quantitative yield. This intermediate enabled straightforward elaboration of the ATP-binding fragment, as N-Boc-1,4-diaminobutane was subsequently alkylated with intermediate 4 to generate the chain-extended linker precursor 5. The use of DIPEA instead of triethylamine suppressed

• undesired alkylation of the base and significantly improved the isolated yield up to 84%. Introduction of an acetic acid handle was then achieved via alkylation with bromoacetic acid under DIPEA mediation, giving intermediate 6, which served as the common attachment point for linkers 7–10 (for full

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

• is less sterically hindered (%Vbur = 62.3%). For comparison, the site with the lowest BDE has an intermediate value for %Vbur of 65.4%. Compounds 5 and 6 Allen and Lambert [42] reported the tropylium ion-mediated α-cyanation of amines, including compounds 5 and 6. In the case of compound 5, the

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• unsymmetrical intermediate hydroxy-butynylphosphate tweezer and any azido histone peptide will lead to the desired truncated tweezer conjugate. This concept proved feasible and was performed with H3 peptides of different lengths to produce new peptide tweezer conjugates designed to target near and far lysines

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• intermediate 12 with the anti-face of the benzoate to give compound 14. Similarly, the chloride anion attacks by SN2-type the epoxide ring of intermediate 15 to give the sole product 16. The structure of acetate 11 was investigated using 1D (1H and 13C) and 2D (COSY, NOESY, NOE-diff, and HMQC) NMR

• each elementary reaction step along these routes were computed. The acid-mediated ring-opening reaction in the isomeric epoxides 9, initiated by protonation, can follow two possible pathways – either along the intermediate 12 or along the intermediate 15. There is a possibility of two products being

• formed in both pathways. Free energy computations indicate that the intermediate 12 is thermodynamically more stable by 4.9 kcal mol−1 compared to intermediate 15. The nucleophilic attack by chloride ion bifurcates into two paths, namely C1- (route a) and C2-attacks (route b) for intermediates 12 and 15

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• trisquadricyclane. Even though the reaction can be monitored by photometry or by in situ 1H NMR spectroscopy, unambiguous assignment of the distinct intermediate mono- and bisquadricyclanes was not possible because of signal overlap. In contrast, this shortcoming is circumvented with in situ 19F NMR-spectroscopic

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• proved to be suitable for the cyclization towards 35 and the eventual macrocyclization was achieved via coupling of the alkyl bromide unit with the thioester. Mechanistically, this reaction is enabled by the formation of an intermediate alkylzinc halide, which is produced by single electron transfer

• described in Scheme 6 below (R1 and R2 in equatorial position). From 43, the methylene unit in 44 was formed by Pd(0)-mediated generation of a π-allyl–palladium intermediate, followed by reductive termination (Tsuji-reduction), alongside the substrate-controlled alignment of the adjacent methyl substituent

• . Protection of the free alcohol unit enabled the transformation towards 55, which involved the reduction of lactone to lactole, protection of the alcohol as acetate, BF3·Et2O-mediated C-allylation of the aldehyde (via oxocarbenium intermediate) and cyclization (oxy-Michael reaction). Hydroboration–oxidation

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• both for the generation of free hydroxylamine and for the subsequent synthesis of PCP HA. The resulting tetrapotassium hydroxamate intermediate was then acidified with a 10% HCl solution, inducing precipitation of the tetrahydroxamic acid form. PCP HA was isolated as a grey solid in high yield (95