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

• –99% using LiAlH4 reduction (Scheme 3). Unexpectedly, reduction of 13d and 13f led to the same compound, the dehalogenated derivative 17d in 96% and 51% yield, respectively, presumably through nucleophilic aromatic substitution [29]. Oxidation of alcohols 17a–d using pyridinium chlorochromate (PCC

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

• inhibition of root growth of Arabidopsis thaliana. The RLIT data is compared with those previously reported for two series of compounds having the same substitution pattern at C-22 but different structure in ring A. This comparison revealed that a 2α,3α-dihydroxy configuration is more active than a 3

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

• therefore more likely that steric effects in the transition state for the putative cyclization to give 8 are prohibitive. Indeed, we were unable to locate a transition state for this process computationally. In order to test the limits of the reaction with related substitution patterns in this process, we

• shift by a remarkable 1.0 ppm. Similarly, in the 13C NMR spectrum, the ortho-disubsituted ring produces 6 aromatic and 2 aliphatic signals, rather than the 4 aromatic and 1 aliphatic signals that would be expected given the symmetrical aromatic substitution pattern. These data indicate that the ortho

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

• of a product exhibiting reversed polarity (20). Conversely, when no α-aryl substitution is present, increased electron density remains at the C2 position, favoring the typical (3 + 2) cycloaddition pathway leading to product 19. In [48], the authors studied the reason for the complete change in

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

• . Systematic tuning of photochromic properties is the focus of several articles in this thematic issue. Kitagawa, Kobatake, and co-workers [15] studied the effect of the substitution position of aryl groups on the thermal back-reaction of azadiarylethene photoswitches. Simeth and co-workers [16] present a

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

• . These properties encompass the site of metabolism [25][27], the strengths of hydrogen bond donors and acceptors [28][29][30], the regioselectivity of electrophilic aromatic substitution reactions [10], C–H pKa values [3], and electro- and nucleophilicity [31]. Building on the methodology from Finkelmann

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

• nucleophilic aromatic substitution with thiophenols followed by oxidation with m-chloroperbenzoic acid (mCPBA). The scope of the reactions was explored, demonstrating high yields across a variety of functional groups and substituents. Optimized conditions enabled selective oxidation of thioaryl groups to

• as promising antimicrobial agents and provide new insights into their mechanism of action. Keywords: antimicrobial activity; aromatic nucleophilic substitution; isoxazoles; oxidation; sulfonylisoxazoles; Introduction The isoxazole ring represents an important building block for the synthesis of

• -sulfonylisoxazoles based on nucleophilic aromatic substitution of the nitro group in 3-EWG-5-nitroisoxazoles by treatment with thiophenols as S-nucleophiles and subsequent oxidation of the thioaryl group (Scheme 1, approach D). Previously, we reported that 3-EWG-5-nitroisoxazoles readily react with various N,O,S

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

• (I). Indeed, the Friedel–Crafts acetylation of cymantrene, a typical electrophilic aromatic substitution reaction, is much slower than that of ferrocene. Consequently, vinylcymantrenes are electron-deficient olefins and less reactive in olefin metathesis. For this reason, the present AMD/KR reactions

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

• hindrance induced by the fluoro substituents in the ortho positions [54]. It should be noted that there is only very limited data available to compare the effect of the substitution pattern on the half-life of aryl-substituted norbornadienes to support this interpretation [55]. However, the effect of ortho

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

• –Kishi (NHK) coupling and Pd-mediated cyclization. Fragment 31 was synthesized from known precursor 28 [74] in 9 steps via MMTr-protection, replacement of the Bn- with TBDMS-protecting groups, hydroxylation of sulfone 29 to alcohol 30, tosylation, bromide substitution, acidic MMTr-cleavage and DMP

• )/Cr(II)-mediated coupling of 1-bromo-2-trimethylsilylethene, acidic cleavage of the remaining cyclohexylidene ring, TBDMS-protection of the three alcohol units and electrophilic substitution of the silyl moiety to afford vinyl iodide 103 was applied. Eventually, ester 103 was reduced to target

• formation of 252. Next, conditions reported by Kishi and co-workers were applied for the nucleophilic substitution of the chloride by the oxygen from the tetrahydrofuran ring towards 253 [94], before an adjacent secondary alcohol group reopened the bicyclic cationic intermediate. Cleavage of the TBDMS

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

• first enantioselective C–H amination of arenes catalyzed by a chiral phosphoric acid. Thus, this nucleophilic aromatic substitution reaction not only enables the synthesis of compounds bearing two chiral N-aryl axes but also provides a viable alternative to metal-catalyzed C–N cross-coupling reactions

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

• major strategy involves fused-ring modification, wherein heteroatoms such as azo or thiol groups are introduced either linearly at the 4,5-position or laterally at the 5,6-position of the naphthalimide ring [32][33][34][35][36][37]. A second approach involves positional substitution, shifting functional

• enhancing lysosomal membrane permeability and aqueous solubility [42]. Interestingly, for the first time, N-(n-octyl) chain substitution has been shown to demonstrate remarkable anticancer activity, particularly through tyrosine kinase inhibition, without significant DNA intercalation [43]. Among these

• derivatives, N-(n-octyl) substitution at the 6-position exhibits a more pronounced effect as compared to octyl substitutions linked to the imide nitrogen of the naphthalimide ring [44]. Furthermore, comparative studies between sulfur- and selenium-containing naphthalimide analogues revealed that the selenium

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

• substitution patterns were selected as the starting materials to enable further preparation of the respective mono-, di- and tetrapropargylated calix[4]arene tetraamines and their derivatives. The silylation of propargyl ethers 1–5 was first attempted using tert-butyldimethylsilyl chloride (TBSCl) and the

• conditions. In line with this, compounds 8–10 having less sterically hindered narrow-rim substitution patterns were found to be more resistant to side reactions during wide-rim nitration as well as to the target exhaustive nitration itself. These reactions required a higher nitric acid concentration of ≈2.5

• only the reaction time increased (Scheme 2). The 1D NMR spectra for the dinitrocalix[4]arenes 12 and 13 provided no definitive data on the substitution patterns at their wide-rims except for the presence of two nitro groups in the distal aromatic units. To localize the nitro groups in the structures of

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• therapeutic potential. Analyzing the structure–activity relationship with respect to the HeLa cancer cell line, it can be seen that among the diphenyloxazolopyridine derivatives, the substitution of the piperidine functional motif at position 7 in compound 1 by 4-ethylpiperazine leads to a decrease in the

• cytotoxicity by two times (compound 3). Whereas its substitution by morpholine lead to inactive compound 2. The same result was obtained by substituting 2-piperidin-1-ylpropylamine in 1 with hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one (6). However, methylation of the phenyl group at the 5-position of

• addition of a 4-chlorophenyl group instead of the methyl group as a functional motif at position 7 (4) sharply reduced the cytotoxicity of compound 1. The substitution of piperidine by morpholine in this motif in compound 4 resulted in a 2-fold increase in the activity of the obtained derivative 5. However

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• obtained products with LiAlH4 leads to a substitution of the attached nucleophilic moiety with hydrogen in good yields. Keywords: aminoalkylation; aminosulfones; ketosulfones; pyrrolidines; Introduction Sulfones and sulfonic acids are valuable structural motifs in organic chemistry, notable for their

• commonly achieved by a classic nucleophilic substitution of a leaving group at the β-position relative to the N-protected nitrogen (Figure 2a). While this approach addresses most needs of targeted synthesis, developing alternative methods from inexpensive starting materials via domino-processes, allowing

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

• hand, the brightness BCPL values were calculated to be 30.75 M−1 cm−1 for 5b and 31.46 M−1 cm−1 for 6b. This comprehensive understanding of the influence of phenyl substitution and helical extension on the CPL features of oxaza[n]helicenes provides a valuable roadmap for designing future CPL- emitters

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• a major objective in contemporary synthetic chemistry [12][13][14][15][16]. Despite their ubiquity, amides are notoriously unreactive toward classical acyl-substitution pathways. This inertness arises from a strong amidic resonance, which confers partial C=N double-bond character and a planar

• % yield. Mechanistically, WCl6 coordinates with Phen to generate the active tungsten species [G]. In cooperation with TMSCl as a Lewis acid, the catalyst activates the amide toward nucleophilic attack by forming an electron-deficient intermediate H that readily undergoes substitution. Palladium complexes

• of 2 equivalents of TCCA as a chlorinating reagent and 2.5 equivalents of lithium benzoate (LiOBz) as a base, primary amides are converted into the corresponding N,N-dichloroamide intermediates 46, which then undergo smooth nucleophilic acyl substitution with alcohols to afford esters. The substrate

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• literature data on reactivity of 5-azidopentyne derivatives in intramolecular Huisgen cycloaddition reactions are contradictory. Some authors successfully obtained 5-azidopentyne derivatives upon nucleophilic substitution at 80 °C in DMF, and additional heating at 170 °C was necessary for cyclization to

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• that, in analogy to related compounds 114 and 131, an initial oxidative event at C-17 (145a) results in the 1,2-methyl group shift (see Scheme 35A). Capture of the tertiary carbocation by a peroxy-species would deliver 145b, which upon C-11 hydroxylation and SN’ substitution by the hydroperoxide could

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• ). Substitution of the meta-chlorine with fluorine also favored the exo-isomer (compound 4j, 70%, endo/exo 1:2), similar to 4l. The presence of an electron-withdrawing group at the meta-position of the maleimide’s N-aryl group likely facilitates exo-isomer formation. Reactions with maleimides containing meta-NO2

• -halogen substitution in aromatic maleimides was found to preferentially direct the cycloaddition toward the formation of exo-isomers. The structures of all obtained diastereomers were thoroughly characterized by 1H and 13C NMR spectroscopy. Single crystal XRD analysis of two representative compounds

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• also profoundly influences the electronic character of the aromatic ring. The ring becomes more electron-rich, akin to substitution with electron-donating groups, and exhibits distinct distortions in the bond lengths of the ring, consistent with localization of the π-system (i.e., dearomatization

• , display remarkable substitution inertness, even toward strong π-acids and good σ-donors. The substitution rate being relatively independent of the incoming ligand is consistent with a dissociative substitution mechanism. Typically, coordination occurs at positions that minimally disrupt the arene π-system

• metal center with α-pinene and subsequent ligand substitution proceeds with retention of configuration, the corresponding Mo(0) complex undergoes racemization during substitution (Scheme 2A). This obstacle was overcome by a redox-based approach: oxidation of the Mo(0)–α-pinene complex with iodine to a

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• decarboxylase and as a therapeutic agent against African trypanosomiasis. Beyond its pharmacological importance, DFMO provides a valuable model for examining how fluorine substitution governs molecular conformation. A comprehensive quantum-chemical study was performed to elucidate the origins of DFMO’s

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• substitution pattern along the plane of symmetry, is known as planar chirality, as seen in metallocene and cyclophanes. Molecules containing planar chirality have greater relevance in materials science and stereoselective transformations [12][13]. The fourth branch of the chiral tree is helical chirality. A

• nucleophilic substitution reactions (Scheme 5). A stereochemical model was proposed for the phospha-Michael addition, indicating that enantioselectivity was primarily influenced by steric effects arising from hydrogen bonding and ion pairing between the peptide mimetic phosphonium salt (PPS)-activated

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• effect is a clear indication that the OH group is engaged in an IMHB [19]. Furthermore, the relatively small isotope effect on C11 and C12 also indicates a hydrogen bond to nitrogen (i.e., nitrogen as hydrogen bond acceptor), as the effect caused solely by NH(D) substitution would have been expected to

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• Scheme 5A, dimethyl sulfoxide (DMSO) did not react with the benzyl bromide and instead only returned the starting material. The addition of 1.2 equivalents of silver nitrate promoted the substitution of the benzyl bromide with DMSO to yield an alkoxysulfonium ion 8 [22]. Following substitution, the