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

• -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

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

• -hydroxyquinoline scaffolds bearing both C6-halogen and γ-(3,4-dimethoxyphenyl)propanoic acid motifs. Existing approaches to such derivatives comprise typically multiple steps, are limited in scope, or require harsh reaction conditions, restricting their application in rapid analogue generation. The combination of

• activity [33]. Halogen substituents in this position have been shown to modulate antibacterial, antiviral, and antiproliferative activities, likely through electronic effects and improved target binding. The C3 position was functionalized with a propanoic acid moiety, explored in both its open-chain (acid

• , cyanoacrylates, and others. The second approach consists of the Michael 1,4-addition of the corresponding acetate or malonate anion to 3-arylidenequinolinedione. Both strategies were evaluated in subsequent studies. To implement these routes, 6-halogen-4-hydroxyquinoline-2-ones 2a–c were prepared. The synthesis

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

• methods for phosphorus chemicals that do not depend on white phosphorus or phosphorus chloride have been developed to reduce energy consumption and environmental hazards. For example, Montchamp’s group and Yang’s group have focused on using sodium phosphinate as an alternative to PCl3, and various halogen

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

• color to be retained in its sulfonated derivatives [27][28][29]. As shown in Table 1, the pKa values of 9 and 10 each have first pKa values about 0.4 pK units below their non-brominated derivatives, indicating the impact of the electron-withdrawing halogen substituents [30]. Conclusion Overall, the

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• diminished yields (68% and 88%, respectively; Table 1, entries 9 and 10). We tentatively attribute the inferior performance of NCS to its lower halogen-transfer efficiency and oxidation potential under the present conditions, which likely result in a less efficient generation of the key electrophilic sulfur

• species and in increased competitive decomposition. In contrast, the more strongly oxidizing TCCA tends to promote non-productive overoxidation pathways, thus also failing to match the efficiency of NBS. These results underscore the critical role of halogen source and oxidative strength in modulating the

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

• synthesized and screened in asymmetric Mannich reaction. The reaction of aromatic imines with malonates in the presence of amino acid-derived catalysts gave Mannich adducts in very high enantiomeric purities (up to 98% ee). It is proposed that a network of hydrogen and halogen bonds with Lewis bases, together

• efficient in Mannich reactions, as demonstrated by our studies [18] and those of others [19][20][21]. Halogen bonding has also been introduced to further broaden the field of noncovalent interactions. Despite the limited number of asymmetric transformations driven solely by halogen-bond activation [22

• ], halogen bonding is more frequently employed as a component of multifunctional catalytic systems [23][24][25]. Multifunctionality of the catalyst is essential to intensify weak noncovalent interactions. Results and Discussion As a continuation of our previous studies [18][24], we now report an asymmetric

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

• (±)-dihydrolysergic acid (Scheme 11). Smith and co-workers recently reported a six-step synthesis of (±)-lysergic acid [77]. In contrast to previous approaches, the pyridine was introduced via a magnesium–halogen exchange of pyridyl iodide 93, followed by addition to aldehyde 94. Subsequent reduction of the resulting

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

• for future development. Keywords: halogen atom transfer; photoredox; radical; total synthesis; zirconium; Introduction Zirconium, a transition metal in the same group as titanium, has been employed across research fields and in medical applications owing to its distinctive physical and chemical

• Schwartz’s reagent (Scheme 1) [7][8]. When compound 2, bearing an alkyl halide and an olefin moiety, was treated with triethylborane and Schwartz’s reagent in tetrahydrofuran, a halogen atom transfer (XAT) occurred at the alkyl halide, generating alkyl radical 3. This radical subsequently underwent

• , Schwartz’s reagent reacts with triethylborane to generate a low-valent zirconium complex 5. This complex abstracts the halogen atom from the alkyl halide, forming alkyl radical 8. The radical then cyclizes onto the olefin, and the resulting radical intermediate undergoes hydrogen atom transfer (HAT) from

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

• chlorine is associated with an increase in energy of the lowest unoccupied molecular orbital of halogen molecules and a decrease in their electrophilicity. Therefore, if an electrophilic mechanism takes place, iodine apparently reacts with the main conformer faster than a transition to conformer 2' may

• possibility of i-halogenation via a chain radical mechanism (Scheme 3). The initiation stage includes an oxidation of anion 2 into the corresponding radical 13 which in turn reacts with halogens to form products 4a,b and a halogen atom which can also oxidize the anion. Quantum chemical calculations revealed

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

• -catalyzed C–halogen bond formation (Figure 3E) [36]. Exchange reactions were reviewed by Evano and Nitelet in 2018 (Figure 3F) [37]. In 2020, Gandelman and co-workers provided an overview of decarboxylative chlorination reactions of carboxylic acids (Figure 3G) [38]. Hoveyda’s 2023 review highlights

• reported the use of (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides (Scheme 12) [64]. A variety of alkenyl chlorides was obtained in good yields, with functional groups such as esters and boronates well tolerated. When camphor was treated with (PhO)3P·Cl2 (TPPCl2), the two

• Finkelstein-type halide exchange reaction (Scheme 23). This strategy leverages the decreasing bond-dissociation energies across the halogen series – C–Cl (D298(C−Cl) = 395 kJ mol−1) and C–Br (D298(C–Br) = 318 kJ mol−1) bonds compared to the C–I bond (D298(C–I) = 253 kJ mol−1) to drive the substitution of

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

• –halogen exchange in the ABC-fragment 38 followed by 1,2-addition to the ketone moiety in the F-ring fragment 42. Protection group manipulations allowed for the union of both fragments to advanced intermediate 43 in three steps in 42%, setting the stage for the key cyclization reactions in this sequence

• 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

• coupling was carried out via lithium–halogen exchange, 1,2-addition, and subsequent oxidation to give ketone 48. Photoinduced excited-state Nazarov cyclization installed the cyclopentenone C-ring with correct stereoconfiguration at C9 and C10 in excellent yield. Ketone reduction and global deprotection

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• ; and subsequent conversion of the ketone in 20 to the vinyl iodide in 21 – via hydrazone formation, lithium–halogen exchange, and final nucleophilic substitution – secured the Norrish–Yang cyclization precursor 22. Following systematic optimization of reaction conditions, irradiation of 22 with 100 W

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can

• chiral halogenated lactones, which could be useful in the enantioselective synthesis of valuable drug precursors. The syntheses feature the use of readily available and cheap starting materials, and we have also demonstrated some of these transformations on a gram scale. Halogen-containing butyrolactone

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

• transferred to the radical. Important processes of this kind are hydrogen atom transfer (HAT) and halogen atom abstraction. An intramolecular group transfer reaction can result in the net migration of a functional group. Addition of a radical to a π-bond (carbon–carbon or carbon–heteroatom) is another common

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• decided to prepare also the same molecules with hydrogen instead of the chlorine in meta position of the anilino group. Our previous work on DB18 suggested indeed that the chlorine atom is implicated in intramolecular halogen–π interaction, ending in a conformational constraint and ligand rigidity [24

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D

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

• have been induced by addition of external halogen or selenium electrophiles and Brønsted acids. This encouraged us to develop a methodology involving a copper-catalyzed terminal alkyne arylation of propargylsilanes by diaryl-λ3-iodanes, followed by 1,2-silyl shift and terminated by nucleophile addition

• using the symmetrical dithiophen-2-yliodonium p-tosylate (I-7). It should be noted that all products 8 were obtained with exclusive (E)-selectivity. Tetrahydrofuran 8a and some analogous compounds could be synthesized previously from alcohol 7d, but in two steps, employing a halogen electrophile-induced

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

• (37) followed by reduction with Zn/Ba(OH)2 and partial re-oxidation (Scheme 12A) [52]. They can also be obtained from o-halogenated benzyl bromides 40 by lithium–halogen exchange followed by nucleophilic substitution and a second lithium–halogen exchange with iodine (Scheme 12B) or by nickel-catalysed

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• , Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan 10.3762/bjoc.21.138 Abstract In single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one and the thione analogue, a unique association based on a halogen–π interaction was detected. In racemic and optically pure

• N-(2-bromo- or 2-chlorophenyl)quinolin-2-ones, homochiral layered polymers, which consist of (P)- or (M)-atropisomers, were formed through intermolecular halogen–π association. The halogen–π association in the racemates is due to a halogen bond (C–X···π) between a σ-hole on the halogen atom and a π

• -electron on the quinolinone benzene ring, while that in optically pure forms is caused by an n–π* interaction between a lone electron pair on the halogen atom and a π* orbital of the quinolinone. In contrast to the formation of the homochiral layered polymer in quinolinones, in racemic N-(2-bromophenyl

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• halogen atom transfer (XAT) agent [17][18]. Standard reduction potentials illustrate that hypophosphite is a powerful four-electron reductant [19]. Our previous studies have proved that NaH2PO2 can be a selective reducing agent in the catalyst-free reductive amination process [20][21][22] that can impart

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• ], hydrogen atom transfer [22], halogen atom transfer [23], and energy transfer catalysis [24][25] – have been established as powerful additions to the arsenal of photon-driven reactions. Three articles in this thematic issue exemplify this: The Molloy group developed an intramolecular [2 + 2]-cycloaddition

• of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• to the low basicity of the proton-accepting nitrogen atom, the KE* form spontaneously goes to E*, which closes the channel to the twisting region. On the other side there is substantial number of papers describing the very long-lived cis isomers in ortho-halogen-substituted azobenzenes [38][85][86

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

• to a potentially even larger library of amide isosteres. The scope of the carbon nucleophiles is very broad and includes alkyls, alkenyls, alkynyls, aryls and heteroaryls (e.g., pyridine, indole, thiophene), as well as (poly)substituted phenyls bearing a nitrile or halogen(s). On the other hand, the

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• C–C or C–heteroatom bonds. The incorporation of HAT strategies into the functionalization of C–H bonds represents a significant advancement in synthetic organic chemistry for their high atom economy and step economy. HAT reagents (HR), including alkoxyl, acyloxyl, halogen radicals, and amidyl

• require electrophilic heterocycles. These limitations hinder the broader application of such systems. Alexanian’s group modified amidyl radical precursors by incorporating halogen atoms, transforming them into bifunctional reagents. The HAT component of amidyl radical precursors was facilitated by amidyl

• radicals, while halogenation was promoted by the introduced halogen atom [26]. In 2014, Alexanian’s group reported a site-selective aliphatic C–H bromination utilizing modified HRP as both the bromination reagent and HAT reagent (Scheme 11) [25]. Initiated by visible light, HRP-10 underwent homolytic

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• azulene-embedded PAHs. This approach requires a halogen-functionalized precursor and typically employs a palladium catalyst. Dou and co-workers reported a last-stage intramolecular C–H arylation of substituted indenofluorenes 61 and 62 (Scheme 10) [57]. The palladium-catalysed reaction yielded fused