Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• unrealized. This result places the cyclocondensation reaction that generates compound 968 within a family of three-component reactions of 1,3 dicarbonyl compounds, an aryl aldehyde, and various 1,3 di-nucleophiles (Figure 4). These reactions proceed by an aldol condensation between the dicarbonyl and

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

• from 9 via 10 and 11 using a reported protocol [49], was replaced with an organylselanyl function. Two different organyl selenolates, phenyl selenolate and n-octyl selenolate, derived respectively from diphenyl diselenide [50] and di-n-octyl diselenide [51], were employed as nucleophiles for this

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

• modifications and the use of the obtained compounds as building blocks. We also examined other nucleophiles suitable for the described domino-sequence. Thus, application of ethanol as solvent resulted in a mixture of the desired product 4b with the corresponding intermediate C (NMR ratio 88:12), however, longer

• , piperidine, morpholine, or 1,2,3,4-tetrahydroisoquinoline (THIQ). A special curiosity was associated with the use of mercaptans as nucleophiles for the synthesis of aminobutanes 4 containing both sulfide and sulfone moieties. To our delight, an excess of butylmercaptan or thiophenol readily afforded products

• of the pyrrolidines 2. In this way, the hydride anion was formally added to the list of possible nucleophiles (H-, N-, O-, S-). Conclusion In conclusion, we developed a practical route to the novel skeleton of N,N-dialkyl-3-(sulfonyl)butan-1-amines from β-ketosulfones. The proposed approach exploits

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

• enabled the formation of ethyl ester 75 and benzoxazole 76 when ethanol and 2-aminophenol were employed as nucleophiles, respectively. Chen et al. recently investigated an environmentally benign approach to amide C–N bond cleavage using electrochemical activation (Scheme 14) [62]. In the presence of

• conditions, several types of fluorinated alcohols were successfully employed as nucleophiles, generating the corresponding esters in good to high yields. Notably, the method displayed excellent chemoselectivity for primary amides. Therefore, multifunctional substrates derived from natural products or

• , completing the electrochemical cycle. Transamidation The Karpoormath group discovered that ammonium salts can serve as nucleophiles for the transamidation of amides without the need for any catalyst, base, or additional reagent (Scheme 15) [63]. Aniline hydrochloride efficiently underwent transamidation with

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

• sulfone complex of W(0) (Scheme 3A) [60]. As established previously [61], protonation of η2-arene ligands bearing electron-withdrawing substituents generates reactive arenium intermediates that react with nucleophiles to furnish disubstituted η2-cyclohexadiene complexes. A second protonation/nucleophilic

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• phosphoric acid and condensed phosphoric acid into a versatile PO2+ phosphorylation agent, (pyridine)2PO2[OTf]. The intermediate reacts with a variety of nucleophiles, providing a redox-neutral method for the flexible synthesis of P(V) compounds (Figure 2C) [44]. Furthermore, Naganawa’s group recently

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• nitro group upon breaking the C–C bond [16][17]. Substituted nitrocyclopropanes in reactions with various nucleophiles form linear precursors for the synthesis of γ-substituted α-aminobutyric acids [18][19], cyclic nitropyrrolines [20] and isoxazoline N-oxides [18]. The nitrocyclopropane fragment is a

• -3,3,3-trichloropropene (1) [40] in reactions with nucleophiles, including those following the formation of cyclic products in tandem transformations [41][42][43][44], methods for obtaining cyclopropane structures based on it are not known. In this way, it seemed desirable to synthesize vicinal

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

• [12][13][14][15][16] nucleophiles (Figure 1). Reactions of cycloheptatrienyl anions with electrophiles present an unexpected approach as the anions possess antiaromatic nature and, therefore, appear to be unstable. Previously we demonstrated that stable hepta(methoxycarbonyl)cycloheptatrienyl

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

• alkenyl chlorides isolated in purities below 85% (not shown) [59]. Transformations of enols to alkenyl chlorides with phosphorous pentachloride (PCl5): β-Chlorovinyl ketones and esters represent highly versatile intermediates, as the chloride moiety is readily displaced by a wide range of nucleophiles

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• . Nucleophilic substitution of the nitro group with sulfur nucleophiles, including thioacetate or disulfide anions as well as thioacetamide, yielded bis(thiophen-3-yl)disulfide and sulfide derivatives. The disulfide served as a suitable precursor for the preparation of 3-alkylthio-substituted thiophene-2,5

• TTs from the activated 3-nitrosubstituted thiophenes [29][30]. This strategy provides an effective access to the 3-hydroxy-TTs via the nucleophilic substitution of the nitro group in 3-nitrothiophene precursors using S-nucleophiles, such as alkyl thioglycolates or mercaptoacetone (Scheme 1, route V

• addition to potassium thioacetate, the reactivity of ester 1 was investigated with other related S-nucleophiles, such as potassium ethyl xanthate (KSC(S)OEt), sodium diethyldithiocarbamate (NaSC(S)NEt2) as well as thioacetamide in the presence of K2CO3 and Na2S2 (Table 1, entries 2–5). In each case, the

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• their subsequent reaction with O-nucleophiles in the second chamber. The method is easy to setup, control and gives access to new haloacetimidates under mild conditions, similar to the ones used for the synthesis of the more commonly used trichloroacetimidates. Keywords: gaseous reagents; glycosyl

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• method for the enantioselective α-C(sp3) alkenylation of ketones containing imidazole auxiliaries (Scheme 10) [24]. The transformation was catalyzed by a chiral-at-rhodium Lewis acid 42. A variety of ketone electrophiles 40 and alkenyl trifluoroborate nucleophiles 41 were converted to the corresponding α

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• conditions, the authors attenuated the silver catalyst’s activity through ligand addition. This allowed for a umpolung addition of the substrate 87, affording six-membered spirocyclic intermediate 88. When the NFSI was used as ligand without nucleophiles, the tricyclic azepinoindole 89 was obtained via a

• was used as the ligand and amides as nucleophiles, the spirocyclic indole framework 91 was obtained via the capture of imine intermediate 88. When the PPh3 was used as ligand in the absence of nucleophiles, the substrate 87 with an unprotected indole nitrogen facilitated the formation of intermediate

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• nucleophiles [7][8][9][10][11], radicals [12][13][14][15] and electrophiles [16][17][18] to give cyclobutanes and cyclobutenes [19][20], which are building blocks in regio- and stereoselective synthesis [21][22][23][24][25][26][27] (Scheme 1a). Additionally, BCB has been used in bioconjugation due to its high

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter

• linker provides entry to 1,2,3,6-tetrahydropyridines. Additionally, in the absence of internal nucleophiles, this methodology yields aryl-substituted 1,3-dienes. This work introduces a palladium-free, single-step alternative to multistep heterocycle construction from propargylsilanes and highlights the

• described by us recently, among other possible transformations [21][22]. Interestingly, the addition of O-nucleophiles to form 1,3-carbofunctionalization products, can only be achieved in an intramolecular fashion. In the presence of an excess (5 equiv) of external an O-nucleophile R–OX (alcohol, carboxylic

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• suitably electrophilic substrate at the carboxylic acid oxidation level provides an acylazolium species B, which typically reacts directly with nucleophiles or may first be transformed into the corresponding enolate derivative. Regardless of the individual pathway, NHC-catalyzed reactions of this type

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• selectivity in glycosylations with various types of nucleophiles [67][68]. This remarkable stereoselectivity has been attributed to intermolecular hydrogen bonding, which forms a transient tether between the glycosyl donor and acceptor, thereby guiding the reaction towards a preferred stereochemical outcome

• reduced reaction temperatures (−20 to −60 °C), N-phenyl trifluoroacetimidate (PTFA) donors are sufficiently stable to be used in glycosylation reactions at 0 °C or ambient temperature, while remaining reactive enough to glycosylate conformationally hindered nucleophiles in the presence of catalytic TMSOTf

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• nucleophiles in the DKR of various bridged biaryls bearing different linkages to give diverse nitrogen heterocycle-substituted atropoisomeric biaryls. In 2021, our group achieved the catalytic enantioselective DKR of biaryl lactones 46 with α-acidic isocyanides (Scheme 8a) [48]. By using Ag2CO3 and cinchonine

• lactones with carbon nucleophiles. The success lies in the tandem enantioselective ring-opening of lactones with α-acidic isocyanides, followed by a rapid cyclization driven by aromatization, overcoming the long-standing stereochemical leakage problem caused by the undesired lactol formation [45

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• -, particularly 2-methylideneoxetanes have become valuable intermediates in oxetane chemistry as they readily undergo a variety of chemical transformations, including ring-opening reactions with nucleophiles, epoxidations, cyclopropanations and [3 + 2] cycloadditions with nitrile oxides [51][52]. In addition

• cell membrane permeability were measured and the results suggested that these substrates might be promising bioisosteric replacements for thioesters. Five years later, the research group expanded the scope of this methodology to include alcohols as the nucleophiles (Scheme 35) [85], thus avoiding the

• years later, the group extended the scope of nucleophiles to azoles, sulphoximines (and other HN=S species), phosphites, phosphonites or secondary phosphine oxides, and developed selective reaction conditions for the alternative sulphur–fluoride exchange (SuFEx) pathway by employing hard anionic

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• addition, since condensations are affected by the bimolecular addition as an elementary step, special attention to the concentration of the nucleophiles has to be paid. According to Mayr’s nucleophilicity scales [8][9][10], a nucleophilicity parameter N for the specific S,N-ketene acetal intermediate 4 can

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• engrafted with human erythrocytes, after oral administration of the compounds [5][9]. Triazolopyrazines halogenated on the pyrazine ring represent synthetically useful targets for elaboration of this active scaffold, and the regioselectivity of amine nucleophiles (amongst others) has been explored by Korsik

• -halogenated triazolopyrazines with amine nucleophiles, and the only likely product from reaction with primary amines at room temperature. Biological studies All compounds (1–15) were assayed for antimalarial activity against the chloroquine sensitive P. falciparum 3D7 strain, and a preliminary assessment of

• C20H2635ClN6NaO2, 439.1620; found, 439.1616. (A) Position numbering on the pyrazine ring of 1,2,4-triazolo[4,3-a]pyrazine. (B) Illustration of ipso- and tele-substitution products for reactions of nucleophiles with 5-halogenated 1,2,4-triazolo[4,3-a]pyrazine, where X = halogen and Nuc = nucleophile. Key COSY