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

• methodology is demonstrated via a one-pot sequence consisting of copper-catalyzed aza-Michael addition followed by base-mediated cyclization and acid-promoted aerobic oxidation to afford quinolinone derivatives (Scheme 4) [38][39]. In this sequence, 2-aminobenzoate derivatives 4 reacted with α,β-unsaturated

• carbonyl compounds 5 to form the β-amino ketone intermediates, which subsequently underwent base-mediated intramolecular cyclization using KOt-Bu and air oxidation of the resulting 2,3-dihydro-4(1H)-quinolinone intermediates 7 in the presence of HCl to yield functionalized quinolin-4(1H)-one derivatives 6

• cyclization. Scheme 9 summarizes representative examples in which copper acts as a Lewis acid to promote the aza-Michael addition and subsequently enables annulation to construct diverse N-heterocycles. As shown in Scheme 9a, Singh et al. reported that a Pybox-diPh–Cu catalytic system enables the one-pot

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

• synthesis of 5,6-carboxylated SiRs generally rely on the prior installation of protected carboxy-containing precursors (Figure 1b), followed by cyclization to construct the SiR framework and subsequent deprotection [41][42][43][44]. In these routes, the strong electron-withdrawing effect of the carboxy

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

• ]. Additionally, intramolecular C–H arylation reactions with N-heteroaromatics can be used to synthesize various functional molecules that serve as ligands for metal extraction [36][37][38][39][40][41]. Our group developed a cyclization reaction for the intramolecular C–H arylation with N-heterocycles, such as

• phenanthroline and quinoline, containing amide groups (Scheme 2a) [38][40]. These reactions efficiently provide the corresponding annulation products; however, it remains difficult to selectively obtain a variety of substituent positions following cyclization. Moreover, these methodologies necessitate the

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

• [4.1.0]heptan-5-one derivative. The acid-catalyzed transformation of which leads to 2-aroyl-3-hydroxy-1H-pyrroles. Keywords: azirines; condensation; cyclization; diazo compounds; pyrroles; Introduction Diazo compounds play a significant role in the synthesis of heterocyclic compounds, which explains

• reaction of 2-(diazoacetyl)-2H-azirines 1 with aromatic aldehydes 2, which does not terminate in condensation to form an azirinyl-substituted β-hydroxy-α-diazocarbonyl compound 3, but is accompanied by a tandem intramolecular cyclization involving the hydroxy group and the azirine C=N bond to form a

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

• : cyclopropane 5i possessing a chloride as a leaving group underwent highly selective cyclization to deliver the stereodefined borylated cyclopentane 6k in high 84% yield as a single diastereomer. The relative configuration of 6k was unambiguously established by X-ray crystallographic analysis of an osmylated

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

• bond formation and cyclization. Scheme 5 depicts a hypothetical rationalization of the process. Reaction of isatin (1) with ethylenediamine (23) should initially form the imine 26. Its reaction with a second molecule of isatine should lead to the diimine 24. Under the reaction conditions both imines 26

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

• 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

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

• crude 1H NMR spectrum (Supporting Information File 1). We thus used computation to model the cyclization to give products trans-12a and cis-12b, as this substrate appeared to represent a limiting case for both reaction diastereoselectivity and steric tolerance. Given that the reaction takes place in a

• 1b. Minimized structure of dienone 7 (calculated using the PBE0 functional [26] and the def2-SVP basis set [27] (see Supporting Information File 1 for full computational details)). Modeling of cyclization transition states (the solvating acetic acid molecules were omitted for clarity, and the

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

• form pyrrolidine 64. Further treatment of 64 with cinnamaldehyde and N-phenylmaleimide leads to the second (3 + 2) cycloaddition adduct 65. Addition of ICl to 65 results in cyclization involving the styrene groups, which is accompanied by the formation of decahydropyrrolo[2,1,5-cd]indolizine 66. The

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

• hydroxy group allowed the synthesis of compound 1 from 4 in nine steps. Selective acid-mediated 5,10-transannular cyclization of 5 followed by hydration reaction furnished both products 2 and 3 in two steps. Keywords: chemoenzymatic synthesis; chiral pool; isopentenol utilization pathway; terpene

• be widely used as popular starting materials. It is interesting to note that for the biosynthesis of the complex terpenoid skeletons, Nature has evolved a straightforward strategy by the terpene cyclase-catalyzed cyclization of linear oligoprenyl pyrophosphates, which are generally derived from the

• efficient macrocyclization methods, including tetracarbonylnickel-promoted cyclization of allylic dibromide [17][18], copper-mediated intramolecular carbene–olefin cyclization [19], titanium-induced intramolecular carbonyl coupling [20], and organozinc carbenoid-mediated intramolecular cyclopropanation [21

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• in the mixture of melifoliones was increased to a maximum of about 10–15%. Since it was not possible to distinguish or even to separate the isomeric melifoliones using chromatographic methods, their quantitative ratio after cyclization of 5 could only be determined using the 1H NMR spectra. After

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

• 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

• reactions [76][77] for the assembly of fragment 45 (Scheme 6) [78]. Here, 40 and 42 served as the substrates for the allene-Prins reaction towards 43. Notably, the Bz-derivative of 40, 41, served as a starting point for a corresponding halichondrin B analog. The stereoselective course of this cyclization is

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

• ) intermediate, which undergoes intramolecular nucleophilic cyclization (Scheme 15) [54]. This work represents the first synthesis of a compound integrating both helical and axial stereogenic elements, and achieves high diastereoselectivity and enantioselectivity through a cinchona alkaloid-derived squaramide

• organocatalytic approach. The mechanistic study revealed that the reaction proceeds through a stepwise double cyclization process: The first cyclization generates an intermediate bearing a stereogenic axis, while the second cyclization involves dynamic kinetic resolution of the spiral reaction intermediate under

• . Soon after, Shibata and co-workers developed a cycloisomerization strategy that generated various axially chiral polycyclic aromatic hydrocarbons (PAHs) 70 through bond-cleavage followed by successive cyclization reactions with excellent yields and enantioselectivity (Scheme 19) [58]. In 2020, Miller

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

• reaction with 2-naphthol as the dinucleophile is also known [32]. In all cases, the regiochemistry of cyclization is selective and no isomeric products are formed. Conclusion In this report, we confirm the finding by Martinez [28] and Kozlov [29][30] that the three-component reaction originally claimed to

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• dearomatization (review, Xiangbing Qi and co-worker), enamide cyclization (review, Xiao-Ming Zhang et al.), glycosylation (PI-88, Guothi Xiao et al.), [3 + 2 + 1] cycloaddition (tetrahydrofluorenone, Zhi-Xiang Yu et al.), 1,n-enyne cyclization (review, Maosheng Cheng, Lu Yang, Yongxiang Liu et al.), oxidative

• radical cyclization (prostaglandin D2 metabolite, Jun Huang et al.), reductive cyclization cascade (aglacin B, Jina Xiao, Yu Peng et al.), electrochemical cyclization (review, Bin Li, H. N. C. Wong, Xiao-Shui Peng et al.), photochemical reactions (review, Shao-Min Fu, Bo Liu et al.), carbene insertion

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall

• -epoxycarbonyl intermediates. The latter undergo simultaneous deprotection and cyclization by treatment with acid to afford the targeted trans-(±)-taxifolin and its derivatives [19][20][21][22][23][24][25][26][27][28][29][30] (Scheme 1a). Although this synthetic route is efficient, a significant drawback is that

• via Darzens reaction. Subsequent acid-mediated deprotection and cyclization then afforded the target compounds. Compared with the widely used method involving peroxides reported earlier, the present method is highlighted with avoidance of the use of peroxides, therefore enabling safe scale-up and

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• , the treatment with iPrMgBr for preparation of the magnesium alkoxide at highly dilute conditions (10 mM) and sequential cyclization successfully proceeded to provide the C6-iodo-substituted oxacyclophene 1ad in 79% yield. Synthesis of C6-methyl and C6-phenyl-substituted oxacyclophenes The Kumada–Tamao

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

• enables selective oxidative hetero-coupling followed by dehydrative cyclization, furnishing the extended [8]helical scaffold efficiently under mild, oxidant-free conditions. Structural analyses show retained aromaticity, increased helical distortion, and higher configurational stability (≈38 kcal/mol

• 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

• designed coupling partners to control both chemo- and regioselectivity. A finely tuned anodic sequence enables selective oxidative hetero-coupling followed by dehydrative cyclization, delivering extended [8]helical scaffolds efficiently under mild, oxidant-free conditions. Combined experimental and DFT

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

• dioxide in tetrahydrofuran gave vinyl ether 8, which was isolated with 50% yield (Scheme 4). The structure of the product 8 was confirmed by X-ray crystallographic analysis (Figure 3, CCDC 2512653). Formation of 8 apparently occurs via cyclization of alkynal 7. The formation of vinyl ethers has been

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

• by intramolecular cyclization to yield a lactone, which undergoes decarboxylation to produce the corresponding azomethine ylide. In our system, we propose this generated ylide reacts with N-substituted maleimides 3a–p such that the transformation predominantly proceeds via the endo-TS, leading to

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• formation of the cyclic lactone, which predominated under such conditions. These findings suggest that intramolecular attack by the quinolinone OH group, leading to cyclization and formation of pyranoquinolinone, proceeds faster than nucleophilic attack by the external alcohol. Thus, under mild or brief

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

• bromine. The cyclization step from this conformation leads to trans-cyclopropanes. X-ray diffraction analysis data for compounds 2, 3, 9a, and 9b convincingly confirm the accepted structures, the position of cyclopropane protons, and the relative configurations of asymmetric atoms (Figures 2–5). It should

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

• rearrangement and Lewis acid-promoted acetal–ene reaction provided the tetracyclic skeleton 101. With 101 in hands, a 6 step transformation afforded the alkyne 102 in an overall yield of 45%. After obtaining 102, the authors used a free radical reaction to initiate a one-step 6-exo-trig cyclization

• addition to indirectly reduce the heteroaromatic ring of the isoquinoline to yield compound 118. This was followed by desilylation with TBAF and spontaneous intramolecular cyclization to yield the tricyclic 119. With 119 in hand, the double bond was diastereoselectively hydrogenated using Et3SiH and TFA

• sustained interest from synthetic chemists worldwide due to their pronounced antibacterial and anticancer properties. Since their discovery, bis-THIQ scaffolds have been constructed primarily through the Pictet–Spengler reaction, a cyclization strategy that continues to be widely employed in total synthesis

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• -mediated stoichiometric radical reactions Traditionally, the use of Zr complexes in organic reactions had been limited to two-electron processes; however, the first example of a Zr-mediated radical reaction was reported by Oshima et al. in 2001. They reported an intramolecular radical cyclization using

• background of zirconium and its physical properties. Image depicted in the background of Figure 1 was purchased from iStock.com/Just_Super. This content is not subject to CC BY 4.0. Zr-mediated radical cyclization. Ni/Zr-mediated one-pot ketone synthesis. Zirconocene-catalyzed alkylative dimerization of 2

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

• anion). Generation of tertiary aliphatic cations and intramolecular trapping with alkenes or alkynes is well known in the context of polyene cyclizations [155]. Building on Johnson’s earlier work (Scheme 48A) [156], Fañanás and Rodríguez developed an intramolecular cationic cyclization strategy to

• systems, with no successful extension to other ring sizes. The proposed mechanism involves initial generation of a tertiary or benzylic carbocation, followed by intramolecular cyclization with a pendant alkyne to furnish a vinyl cation intermediate. This species is postulated to be trapped by the solvent

• , potentially forming a transient chloronium ion (CH2Cl+). Reaction of this electrophilic intermediate with the BF4− counterion would be expected to yield CH2FCl and BF3; however, the authors did not investigate or confirm the formation of these by-products. In 2006, Cook reported a related cyclization