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

• -bromo-2-nitrobenzaldehyde (4), which can then be directly converted into 1. However, oxidation of the tolyl methyl group into an aldehyde has proved an ongoing challenge. Several syntheses have used a chromium(VI) oxidation to yield the desired product, but the toxic nature of this reagent and the

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

• optoelectronic applications. Experimental General information All reagents and solvents were of commercial reagent grade and used without further purification. Dichloromethane for spectroscopy was purchased from FUJIFILM Wako Pure Chemical Corporation. All compounds were identified by 1H , 13C NMR and ESI-MS. 1H

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

• by several approaches: forming of the CF3-group in a nitrocyclopropane (reaction of 2-nitrocyclopropanecarboxylic acid with sulfur tetrafluoride [31][32]), cyclopropane formation from a nitroethene substrate and a CF3-containing reagent (Corey–Chaykovsky reaction [33]), as well as reactions involving

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

• -methylaspidospermidine (Scheme 27) [95][96]. In a single-step reaction, pyridine 182 was activated with 2-chloroethyl triflate and the resulting pyridinium salt was dearomatized with a Grignard reagent to produce ketone 184. In this step, the Grignard nucleophile added regio- and diastereoselectively at the 2-position

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

• . Zirconium was first discovered by Klaproth in 1789 and subsequently isolated by Berzelius in 1824. In 1952, Wilkinson and Birmingham synthesized zirconium-containing organometallic compounds, pioneering research in organozirconium chemistry [2]. In 1974, Schwartz et al. reported the Schwartz reagent, which

• 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

• direct i-substitution. Conclusion Umpolung reactivity of electron-deficient hexa(methoxycarbonyl)cycloheptatriene through its antiaromatic anion allows to introduce a connection between the cycloheptatriene core and an electrophilic reagent. The cycloheptatrienyl anion mainly exists as a conformer with

• further transformation in the case of allylation. Reactions with diazonium salts mainly involve a vicinal addition of the reagent to the anion and subsequent 1,5-sigmatropic shift, 6π-electrocyclization, and azocyclopropane rearrangement into dihydroindazole derivatives. Analysis of the reaction

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

• corresponding alkyne 50 by elimination with LDA were achieved in superb yields (Scheme 10). Gross and Gloede introduced catechol–PCl3 as an effective reagent for the conversion of ketones to the corresponding alkenyl chlorides [62] (Scheme 11A). Hudrlik later demonstrated that, in the case of 2

• -methylcyclohexanone (54), this reagent markedly alters the product distribution compared to PCl5 [63] (Scheme 11B). However, since the reaction conditions differ significantly, it remains unclear whether the product distribution is driven by the reagent itself or by the reaction conditions employed. In 2007, Prati

• -workers reported the serendipitous discovery that N-acyl-2,3-dihydro-4-pyridinones react with the Vilsmeier reagent to afford the corresponding alkenyl chlorides (Scheme 14) [67]. Notably, dihydropyridones failed to react with POCl₃ in the absence of DMF. In 2003, Wähälä reported a closely related

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• overcome existing constraints in functional group compatibility, efficiency, and reagent scope. In this regard, the direct formation of nitrogen-nitrogen or nitrogen-oxygen bonds presents a significant challenge due to the variety of possible side processes and the low thermodynamic driving force for N–N

• group developed a one-step electrochemical approach to the synthesis of nitro-NNO-azoxy arenes employing ammonium dinitramide (ADN) [87]. The achieved use of ADN, known as prospective chlorine-free green oxidant for aerospace propulsion applications [89][90][91], as both a reagent and an electrolyte is

• compounds with ammonium dinitramide, leading to efficient formation of the nitro-NNO-azoxy group. The developed strategy involves performing the electrosynthesis in an undivided cell under high current density with ADN employed as both a reagent and an electrolyte. The synthesized aliphatic nitro-NNO-azoxy

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• product 11 in 37% yield (Scheme 2). Despite the modest yield, product 11 was transformed to the corresponding tertiary alcohol 12. Removal of the N-Piv group and dehydration with the Burgess reagent [35] led to an inseparable mixture of olefins slightly in favor of the exo-olefin isomer. Dehydration in

• -methylindole [41] in excellent yields. The Negishi cross-coupling reaction with the organozinc reagent prepared from iodoalanine derivative (vide infra) has been used to prepare various aryl-substituted tryptophans in 76–96% yields [42]. In principle, this protocol should be applicable to all the C4–C7

• amino acid reagent that could be removed under non-acidic conditions after the cross-coupling reaction. To this end, we prepared iodo N-Fmoc-ᴅ-alanyl anthranilamide methyl ester 29 from ᴅ-serine. Treatment of prenylindoles 14–17 with iodine and KOH followed by acetylation afforded the corresponding

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

• trifluoroacetoacetate (1) with methyl ketones 2. This reagent has alternative N- and O-reactive centers and thus can react as an N,N- or N,O-dinucleophile, generating in a single synthesis trifluoromethyl octahydropyrido[1,2-a]pyrimidin-6-ones or hexahydrooxazolo[3,2-a]pyridin-5-ones, or both that contain an additional

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• their versatility, eco-friendliness and low cost, the organo hypervalent iodine reagents have become popular in the field of synthetic chemistry in the last few decades. Hydroxy(tosyloxy)iodobenzene (HTIB) is a hypervalent iodine(III) reagent that contains both a hydroxy and a tosyloxy group. Oxidative

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

• 3-position, a copper-mediated C–H activation of position 12 and subsequent protection of the introduced hydroxy moiety to give compound 25 (Scheme 6). Installation of the lactone moiety in 22 was carried out in a three-step sequence via a 1,2-addition of organocerium reagent 26 to the ketone

• manipulations were carried out, the double bond isomerized to position C5–C6, and a reduction was performed, all in an optimized three-step, scalable sequence. Alkylation with phosphonate reagent 36 and subsequent Horner–Wadsworth–Emmons (HWE) reaction formed ring C, followed by an enolate alkylation to forge

• regioselectively desaturated to furnish known phenylsulfonylenamine (Scheme 23). Conversion toward the bromohydrin, treatment with potassium hydride, and subsequent addition of the crotyl-Grignard reagent 75 gave the desired isomer 76 in 22% yield over four steps. More exactly, the diastereomeric piperidine was

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• reagent [20], the key intermediate 8 bearing a butenolide motif was obtained in 76% yield. Next, with the aid of the strong Lewis acid Bi(OTf)3, the regioselective elimination of 8 was achieved to produce the Δ14 olefin intermediate 9 in 86% yield. Afterwards, we evaluated the reactivity of 9 towards

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• , successful macrocyclization was achieved by employing benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as the coupling reagent in DMF at a concentration of 10−3 M. After cleavage from the resin and global side-chain deprotection, the crude cyclic peptides were purified by preparative

• reagent for the challenging head-to-tail macrocyclization step under moderate dilution (10−3 M). This protocol afforded the target cyclic peptides in practical isolated yields (45–70%) and high purity. Comprehensive structural characterization by HRESIMS, NMR, and HPLC confirmed the identity and high

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• route commenced from (−)-pulegone. After introducing oxidation states at C6 and C10 and installing an alkynyl group at C11, oxidative cleavage of a double bond yielded the key propargylic alcohol intermediate 66. This compound underwent a 1,2-addition with alkynyl Grignard reagent 67, and the resulting

• , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• asymmetric conjugate addition was carried out [20][21]. The in situ generated aryl–copper(I) species was obtained under the action of CuBr·Me2S with Grignard reagent 8, and then added to a THF solution of the α,β-unsaturated acyl oxazolidinone 7 at −48 °C. This reaction demonstrated an excellent

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• reagent resulted in complete loss of reactivity (Table 1, entry 12). Further, extending the reaction time had no significant effect on the yield (Table 1, entry 13). Finally, our investigation using various 3d transition metal catalysts such as Ni(OAc)2, Cu(OAc)2, and Co(OAc)2 in place of Pd₂(dba)3 did

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

• donor; haloacetimidates; haloacetonitrile; two-chamber reactor; Introduction Trifluoroacetonitrile is an electrophilic reagent that has seen a variety of uses, mostly for incorporating trifluoromethyl groups into organic compounds [1]. As an example it has been successfully utilized for the synthesis

• [14][15][16][17]. Recently, 2,2,2-trifluoroacetaldehyde O-(aryl)oxime has been introduced as a precursor for trifluoroacetonitrile allowing to work under mild conditions at room temperature (Figure 1) [18]. Whether one prepares a precursor or the actual reagent, a separate setup is needed and hence

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• reagent 118 using trifluoromethanesulfonic acid (TfOH) or TMSOTf as Lewis acids. The authors suggested that the reaction proceeded via the formation of an intermediate 119 followed by reaction with an alcohol nucleophile and a 1,2-carbon migration to produce a cyclopentane derivative 120 with a yield of

• 50% yield. Banerjee et al. [95] demonstrated an alternative method for the synthesis of cyclopentane derivatives. The method included the cleavage of epoxides using Grignard reagents followed by ring contraction. Treatment of epoxide 212 with Grignard reagent through intermediates 213 and 214

• produced aldehyde 215, and further reaction of 215 with the Grignard reagent gave alcohol 216 (Scheme 38). A promising method for the contraction of cyclohexane rings is the semipinacol rearrangement. For the enantioselective total synthesis of (−)-citrinadin A (217) and (+)-citrinadin B (218), the authors

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• with an Ir-catalyzed regioselective C–H borylation developed simultaneously by Ishiyama, Miyaura, Hartwig, and co-workers and Smith and co-workers [26][27]. First, the triflate group of 33 was removed by a Pd-catalyzed reduction with ammonium formate as the reducing reagent. The resulting Boc-protected

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

• reduced form 6, which is sold as a solvent, is an inexpensive commercially available reagent (Scheme 1) [21]. Monohalogenation of LGO giving chloride 7a [22] and bromide 7b [23] is readily achieved in a single step, however, fluorinated 7c, which is a potent inflammasone inhibitor (0.8 ± 0.5 µM), has only

• 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

• using CF3 donors in copper-catalyzed [34], base- and Lewis acid-mediated reactions [35][36][37]. The reaction of enamine 9a with Togni’s reagent (18) and subsequent hydrolysis gave the substituted derivative 19 in 35% yield (qNMR) (Scheme 4). The yield was improved using the N-methylpiperazine-derived

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

• phosphoric acid catalytic system [31]. Aminoalkenes react with Togni’s reagent in the presence of a catalytic amount of CuCl and a chiral phosphoric acid to yield pyrrolidines. Using this methodology, chiral α-quaternary substituted pyrrolidines were synthesized in good yields and excellent

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

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

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

• reagent the 3-(methoxycarbonyl)phenylboronic acid ester 11. All derivatives have spectral and analytical data in agreement with the proposed structures (see experimental section and Supporting Information File 1). Kinase inhibition studies Our molecules have been submitted first to a primary screening

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• efficacious but face significant challenges when applied to non-symmetric systems [24], particularly in achieving regioselectivity. These methods frequently require a particular reagent pair or an excess of one reactant, which limits their efficiency and versatility. In contrast, Baeyer–Mills reactions, which

• avoiding excess reagent, and simplifies purification and scale-up. With the most suitable reaction conditions in hand, the substrate scope was examined. First, the reactivity of different aryl bromides with phenylhydrazine (1a) to form non-symmetric azobenzene was explored (Scheme 1). Most of the