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

• methodologies for the preparation of this class of compounds are of considerable interest. Azides have traditionally been used as protected primary amine equivalents. Therefore, in our previous studies, we employed azides containing eight-membered rings as precursors in the synthesis of C8-aminocyclitols [12

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

• ]. Upon addition of magic blue (5, 7.5 mol %) to a solution of quadricyclane 2f0,3 in CDCl3, the norbornadiene 1f was formed almost quantitatively in addition to very small traces of tri(4-bromophenyl)amine, i.e., the reduced catalyst (see Supporting Information File 1, Figure S12). Discussion A

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• functionalized this position with linkers for the development of HDAC1–3 proteolysis targeting chimeras (PROTACs) [14][18]. Alkyl-linker lengths of approximately 12 atoms and greater were the most effective degraders [18]. We chose the commercially available amine functionalized nanogold particles (Au–NH2

• -labeled HDAC inhibitors could serve as effective fiducial markers in cryo-EM, facilitating the localization of distinct subunits or binding sites within large and flexible multiprotein complexes. HDAC1–3 inhibitor CI-994; HDAC inhibitor–nanogold probe Au–(CI-994); structure of amine-functionalized 1.4 nm

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

• groups from the 5-position to the 6-position to prevent N-acetylation-related side effects and enhance antitumor efficacy [38][39]. Notably, a series of naphthalimide derivatives bearing sulfur-containing secondary or tertiary amine functions at the 6-position of naphthalimide have gained attention, as

• secondary amino functions strongly suppress acetylation and the embedded sulfur function contributes to the apoptosis induction [40][41].The third modification route centres on functional group engineering, in which small amine substituents are replaced with polyamines or long aliphatic chains, thereby

• with water (20 mL) and brine (20 mL). The organic layer was dried with anhydrous MgSO4, filtered and the solvent was evaporated under vacuum. Petroleum ether was added to the residue and triturated. The solid was filtered, affording white amine 11 (500 mg, 48%). mp: 95–97 °C; 1H NMR (400 MHz, CDCl3) δ

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

• ]arenes containing four amino groups at the wide rim and one, two or four propargyl or 2-azidoethyl groups at the narrow rim of the macrocycle, which can be used for expanding functionalization of the calixarene core in the well-known amine acylation (or similar reactions) and CuAAC ‘click’ reactions. Two

• tetraureacalix[4]arenes was obtained. Examination of the 1H NMR spectra of the tetraureas in CDCl3 showed that in most cases triazole heterocycles do not intervene the formation of homo- and heterodimeric capsules by these compounds. Thus, considering the synthetic value of CuAAC and amine transformations, p

• bis(trimethylsilyl)amine (HMDS) with n-butyllithium in THF immediately before the addition of a propargylated calixarene followed by TBSCl. This allowed us to improve the yield of the known calix[4]arene 6 [9] having four silylated propargyl groups at the narrow rim, and to obtain the respective

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

• , and the Strecker amine (aminoethylamine) moieties. Cytisine has been shown to inhibit the proliferation of A549, HepG2, EC109, K562, HL-60, and U937 cells. Following a 48 h treatment, IC50 values were approximately 2 mM in HL-60 and U937 cells, whereas higher concentrations were required to inhibit

• combination of the [1,3]oxazolo[4,5-d]pyrimidin-7-amine fragment (structures A and B) with cytisine, glucamine, and aminoethylamine represents a promising strategy for the rational design of multifunctional hybrids with improved biological activity, water solubility, lower toxicity and target engagement

• described methods [14][15][16] as depicted in Scheme 2. The 7-Amino-substituted 1,3-oxazolo[4,5-d]pyrimidines 1–9 were obtained with high yields (65–80%) by the reaction of 2,5-diaryl-7-chloro-1,3-oxazolo[4,5-d]pyrimidines II with the corresponding amine (aminoethylamines [17], cytisine and N-methyl-ᴅ

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

• field is offering diverse methodologies that enable the introduction of either protected nitrogen atoms or aliphatic amine groups. Such diversity has greatly expanded the synthetic arsenal available for constructing aminomethylated compounds. In contrast, methods allowing an aminoethylation process is

• cesium carbonate at 25 °C for 96 h provided higher yield (Table 1, entry 2, 70%). However, heating this mixture at 65 °C for 24 h in a sealed vial gave pure desired 4-methoxy-N,N-dimethyl-3-(phenylsulfonyl)butan-1-amine (4a) in 90% yield and 83% overall yield starting from ketosulfone 1a (Table 1, entry

• solution of dimethylamine did not affect the process and bis-dimethylamino product 4l was readily isolated in 97% yield. The obtained 2-(phenylsulfonyl)butane-1,4-diamines 4l–p represent the biogenic amine putrescine scaffold, incorporating dialkylamino or azaheterocyclic motifs such as pyrrolidine

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

• unsymmetrical oxaza[8]helicenes Building on Zhang’s facile acid-mediated carbazole synthesis [53], in which aniline derivatives react with p-benzoquinone to afford 3-hydroxycarbazoles [54], we employed a closely related substrate. Specifically, N-(p-tolyl)phenanthren-3-amine (2) – prepared from 3

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

• that coordination of the amide oxygen to the Lewis-acidic sites of Nb activates the amide toward nucleophilic attack. Simultaneously, water is pre-adsorbed on the basic oxygen sites of Nb2O5, enabling nucleophilic attack on the activated carbonyl center (D). Following amine release from the resulting

• hydrogen chloride acting as a Lewis acid, enabling nucleophilic attack by the amine to form a tetrahedral intermediate Z. Subsequent intramolecular hydrogen shift, followed by elimination of dimethylamine, affords the protonated transamidation product. In 2021, Lee et al. discovered that carbon dioxide

• reacted smoothly with p-methoxyphenyl (PMP) amine, p-methoxybenzyl (PMB) amine, N-benzyl-N-methylamine, and indole, generating the corresponding amides 99–102 in good to excellent yields. Based on kinetic studies, the authors proposed a plausible mechanism in which the dihydrogen tetrametaphosphate

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

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

• cyclohexene derivatives beyond sulfone and sulfonamide motifs. By combining ester enolate and amine addition sequences, this methodology was subsequently extended to the synthesis of architecturally complex polyheterocyclic frameworks (Scheme 3B) [62]. Such scaffolds are scarcely represented in contemporary

• sufficiently strong, minimally hindered amine bases, such as triethylamine or quinuclidine, favored formation of the 1,4-substituted dearomatized product over simple benzylation. This outcome was rationalized by the involvement of the base in facilitating the 1,5-hydrogen transfer during the rearomatization

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 through a hydrolysis or E2 elimination reaction. The generated phosphoric acid forms a salt with triethylamine. Next, the phenoxy anion activated by the amine undergoes a nucleophilic attack on the phosphorus atom of the salt of phosphoric acid, resulting in the formation of MPP with the

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

• corresponding amine followed by N-tosylation, providing product 10 in 63% yield without altering the enantiomeric excess (Scheme 4). Additionally, product 8g was converted into the chiral phosphine ligand 12 while fully preserving its helical chirality and successfully applied in palladium-catalyzed

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• 2a,c,f in 51–60% yields. Various N-aryl-substituted 2,5-dihydrothiophene-2-carboxamides 1b,d,e,g–j selectively transformed into oxidized products 2b,d,e,g–j in 41–62% yields. Variation of the amine moiety in the cyclooctano-spiroannulated 2-acetyl-N-phenyl-2,5-dihydrothiophene-2-carboxamides showed

• –78% yield. Different N-aryl substituted 2,5-dihydrothiophene-2-carboxamides selectively formed the deacylated products in 55–74% yield. Variation of the amine moiety in the cyclooctano- and cyclohexano-spiroannulated 2-acetyl-N-phenyl-2,5-dihydrothiophene-2-carboxamides resulted in all cases in the

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

• aqueous solutions of 1·HCl may be prepared and stored well in advance of any application or investigation. Subsequently, the apparent pKa values (concentration-based) for 1 were determined to be 8.4 ± 0.1 and 10.7 ± 0.1 for the protonated amine and phenol, respectively, and the calculated pH-dependent

• example, ChemAxon’s calculated clogD7.4 for 1 is 0.84 – substantially lower than the experimental value. Importantly, due to the proximity of the free secondary amine, it appeared plausible that an intramolecular hydrogen bond (IMHB) could be present under certain conditions. A molecule dissolved in water

• the polar nature of this functional group. Based on computationally predicted and experimentally determined secondary deuterium isotope effects, we pinpointed the presence of an IMHB in the neutral form of 1, wherein the phenol proton interacts with the lone pair on the secondary amine. The pKa values

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

• enolized carbonyl compound to an imine derived from an aldehyde or ketone and an amine, has been known for more than hundred years [1] and it has become an important method for creating C–C bonds [2][3][4]. The obtained Mannich bases exhibit a broad spectrum of biological activities [5][6] and have also

• compounds, and catalyst J as a trifluoroacetylated chiral tertiary amine, which lacks iodine. The reaction of imine 1 with dimethyl malonate was selected for the investigation as a model reaction. Based on our previous experience the catalyst screening was carried out in toluene in the presence of 10 mol

• ]. Although basic conditions caused partial racemization during the protection or deprotection step, the Boc-protected amine was obtained in low enantiomeric purity. Chiral HPLC analysis and comparison with an authentic sample revealed the S-configuration of the Mannich adduct [29]. Absolute configurations of

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• -derived pendant group, which exhibited aggregation-enhanced red phosphorescence and CPL properties in the solid states [20], while Yam and co-workers also reported pincer-type platinum(II) complexes containing chiral amine moieties, and investigated their aggregation behavior and chiroptical properties

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

• through sequential nucleophilic attack and intramolecular cyclization. (+)-Isomatrine was subsequently synthesized through catalytic hydrogenation via Rh/C, LAH reduction, and tertiary amine oxidation (Scheme 28). After synthesizing (+)-isomatrine, the effects of catalyst type, loading, temperature, and

• and co-workers reported the first asymmetric total synthesis of (−)-senepodine F, a tetracyclic Lycopodium alkaloid (Scheme 29) [100]. The synthesis commenced with a stereoselective Diels–Alder reaction between compounds 194 and 195 under asymmetric amine catalysis, directly affording the bicyclic

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• -octahydropyridopyrimidinone 4act to 14% was observed. We succeeded in isolating all six products 4 and 5 from the reaction of ester 1, acetone (2a), amine 3 in dioxane (Scheme 1). Octahydropyrido[1,2-a]pyrimidinones 4act and 4att, which were formed in larger quantities, were the first to be isolated: the bicycle 4act

• intermediate is aldol A, which is formed from 3-oxo ester 1 and methyl ketone 2 under the catalysis of amine 3 [24][25][29]. Therefore, we suggest that the formation of octahydropyrido[1,2-a]pyrimidinones 4 and hexahydrooxazolo[3,2-a]pyridones 5 proceeds via the initial formation of aldol A, which then reacts

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

• , vinylogous Mannich reaction of the in situ-generated aldimine condensation product of 49 and amine 50 with trimethylsiloxyfuran 51 generated secondary amine 52 in a diastereomeric ratio of 10:1. To close the piperidine, which is to become the F-ring, six steps were carried out: 1,4-reduction of the

• 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

• , which provided the need for reprotection of the secondary amine moiety, and the alcohol was eliminated to furnish 65 in three steps. Compound 65 already closely resembles the desired target 12 but lacks the oxidation at C11 and the double bond in position C5–C6. Eight more steps were needed for the

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• have been also prepared. The synthesis of key intermediates 6 and 7 is presented in Scheme 1. The reaction of sulfonyl chloride 9 with 1,3-benzodioxol-5-amine or 2,3-dihydro-1,4-benzodioxin-6-amine gave sulfonamides 10 or 11, respectively. N-Methylation with methyl iodide via compounds 12 and 13

• ethylenedioxy moiety attached to positions 7 and 8 of the dibenzo[c,f][1,2]thiazepine (2) core (instead of positions 8 and 9) has also been carried out in the traditional way (Scheme 7). Sulfonamide 39, obtained in the reaction of sulfonyl chloride 9 with 2,3-dihydro-1,4-benzodioxin-5-amine was transformed via

• intermediates 6 and 7. Conditions: i) 1,3-benzodioxol-5-amine (n = 1)/2,3-dihydro-1,4-benzodioxin-6-amine (n = 2), PhNEt2, MeOH, rt, 1 h, 95%/92%; ii) MeI, K2CO3, DMF, 4 h/1 h, 97%/98%; iii) NaOH, MeOH/H2O, reflux, 1 h, 97%/99%; iv) 1. PCl5, DCM, reflux, 8.5 h/9 h; 2. SnCl4, 0–5 °C, 2 h/1 h → rt, 2 h; 76%/84

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• an additive resulted in low reaction yields of the desired product 3a (Table 1, entries 1 and 2). The addition of an aliphatic amine (piperidine) to the reaction medium significantly improved the yields (Table 1, entries 3 and 4). In the absence of NaOAc, only a slight decrease in yield was observed

• disubstitution processes involving sulfur-to-nitrogen displacement, likely promoted by the nucleophilic character of the amine. These limitations are likely due to the reaction conditions employed, including the high temperature and acidic environment, which may favor side reactions over the desired

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

• –C, C–HA bond-forming reactions [36][37]. These chiral NHC catalysts, used to access enantiopure alcohol/amine derivatives, particularly 2° and 3° alcohols/amines, are significant structural motifs in numerous drugs and natural products and have found widespread synthetic applications in medicinal

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

• -mediated N–O bond cleavage afforded carbamate 90. The carbamate was converted to a carbonyl group via Boc deprotection with TFA, oxidation of the resulting amine to the oxime with Na2WO4 and H2O2, and subsequent reduction with TiCl3·HCl to give 91. The LaCl3·2LiCl-mediated methyl addition to the carbonyl

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• three contiguous stereogenic centers (Scheme 1A). The pyran ring was constructed by a RCM reaction [16]. Subsequent functionalization of the alkene to install the 1,2-cis-hydroxy amine required 6 steps from the sterically more demanding side. In continuing our recent interest in accessing unusual

• intermediate 5 will be converted into the final target after installation of the urea and uracil motifs. Accordingly, a nitrone-based latent functionality approach [28] would be tunable from fully substituted tetrahydrofuran-derived nitrone 7. The cis-1,2-hydroxy amine could be derived from oxazoline 6 through