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

• . Halohydrin 14 is yielded with a C1-attack on intermediate 12, while 13 is yielded with a C2-attack. For the formation of halohydrin 14, 12 → 14, the computed reaction and activation free energies are −12.9 and 19.0 kcal mol−1, respectively, while for the 12 → 13 conversion, the computed reaction and

• activation free energies are −12.5 and 23.7 kcal mol−1, respectively. Halohydrin 16 is yielded by a C2-attack on 15, whereas a C1-attack yields 17. For the formation of halohydrin 16, 15 → 16, the computed reaction and activation free energies are −16.2 and 11.2 kcal mol−1, respectively, while for 15 → 17

• conversion, the computed reaction and activation free energies are −17.9 and 18.1 kcal mol−1, respectively. The DFT results are rationally explained and supported our experimental observations, indicating that the methanolysis of both epoxides 9a and 9b preferentially follows the kinetically favourable

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

• the physicochemical parameters of the light energy storage and release, the thermally induced cycloreversion of 2f0,3 was investigated. Analysis of the cycloreversion at different temperatures revealed a half-life, t1/2, of 55 d at 25 °C, an activation enthalpy ΔH = 99.4 kJ/kg, and an activation

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

• , bioactive molecules, and advanced materials. However, its exceptional resonance stabilization renders the C–N bond highly inert, posing a persistent synthetic challenge for its transformation. While twisted amides with distorted C–N bonds have offered useful reactivity enhancements, the selective activation

• of conventional, non-activated amides remains far more difficult. This review summarizes recent advances over the past decade in the activation and cleavage of non-activated amide C–N bonds for their conversion into diverse carboxylic acid derivatives. Key strategies covered include transition-metal

• catalysis, electrophilic activation, strong base-counter-cation systems, and N-based activating groups that enable chemoselective bond cleavage. Together, these developments provide powerful tools for amide functionalization and offer new opportunities for efficient, practical, and selective syntheses

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

• the activation of the diphosphate group and ionisation) [25][37] and Class II (ionisation by olefin or epoxide protonation via a carboxylic acid in the active site) [26][38][39] and their reactions thus are mediated by carbocations and olefins, through careful preorganisation of the linear substrate

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

• in synthetic chemistry. In this review, we delineate the potential of π-bond localization within the aromatic framework as a general strategy for arene activation and dearomatization. Four distinct approaches are discussed, encompassing localization of the arene π-bonds through small-ring annelation

• highlighted. Collectively, these concepts create a roadmap for the development of new strategies that harness π-bond localization to expand the synthetic utility of aromatic compounds. Keywords: arene activation; arene functionalization; dearomatization; metal–arene π-complexes; strained molecules

• arene activation through π-bond localization (Figure 2B). While most examples remain limited to stoichiometric studies probing the structural and reactivity consequences of perturbing aromatic stability, they collectively unveil a rich and largely untapped conceptual space that continues to simmer

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• intermolecular coupling to enhance SOC and suppress non-radiative decay channels, while TADF relies more on donor–acceptor decoupling and smaller ΔEST to lower the thermal activation barrier for RISC. Thus, a key challenge in the field is how to establish adjustable synergy between the molecular-scale

• activation of either RTP or TADF channels in different phases, thus contributing to both fundamental mechanistic studies and the expansion of device applications. In this work, phthalimide (imide) was selected as the acceptor fragment, carbazole as the donor, and a phenylene bridge was introduced to

• construct a twisted D–π–A molecular backbone. This molecular backbone achieves, on the one hand, frontier orbital spatial decoupling through donor–acceptor separation, reducing ΔEST and enabling TADF activation in amorphous environments. On the other hand, it retains the n→π* characteristics of the carbonyl

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

• efficacy [2]. Activation of the 5-HT2AR is thought to induce altered states of consciousness and suppress the default-mode network, a process hypothesized to underlie their clinical benefits [3]. However, classic psychedelics lack receptor selectivity, prompting efforts to develop more selective 5-HT2AR

• selective 5-HT2AR activation in vitro and in vivo [6]. A review published in 2021 provide an in-depth introduction to the pharmacological properties and various applications [7]. More recent examples include the mapping of the cortical correlates of the so-called head-twitch response in mice [8

• . Taken together, this investigation further supports the use of 25CN-NBOH (1) for investigations into the effects of selective 5-HT2AR activation. Our data provides guidance to researchers for the handling and physiochemical properties of the compound when considering its use in various research

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

• previously disclosed a PIDA-mediated oxidative strategy for alcohol incorporation via activation of the S–NH bond (Scheme 1a) [14]. More recently, Wu and co-workers advanced the field by developing a dynamic kinetic resolution protocol for the enantioselective synthesis of sulfinimidate esters from racemic

• limitations, we envisioned that highly electrophilic sulfilimidoyl intermediates – generated in situ via N-halosuccinimide-mediated oxidative activation of sulfenamides – could be directly intercepted by alcohols under basic conditions to furnish structurally diverse sulfinimidate esters [32]. In particular

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

• widely used to achieve these valuable compounds [10][11][12]. Enamine activation was one of the first organocatalytic methods applied in Mannich reactions [13][14]. Concurrently, hydrogen-bond catalysis has emerged as a significant strategy for promoting asymmetric Mannich reactions [15][16]. This has

• 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

• reactions to imines [27]. The model reaction was performed in the presence of various types of catalysts (Figure 1). The syntheses of the catalysts are described in Supporting Information File 1. All catalysts used are amides containing tertiary amino groups, which are needed for the activation of the

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

• limitation requires the design of catalysts that achieve precise electronic complementarity, enabling selective activation across a broad spectrum of aromatic compounds (Scheme 2) [32]. From the standpoint of scalable synthesis, catalyst cost is a major bottleneck in aromatic hydrogenation. Most state-of-the

• heterocycles exhibit strong Lewis basicity, potentially complexing and deactivating catalysts. Consequently, the catalytic hydrogenation of six-membered aromatic heterocycles such as pyridine often requires the introduction of substituents or activation of the aromatic heterocycle to facilitate hydrogenation

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

• iodide 10n failed to give the desired products. In substrate 10o containing both iodide and bromide, selective activation of the alkyl iodide was observed, affording the coupled product in 96% yield. Furthermore, the reaction proceeded smoothly in the presence of alcohols 10p–q and carboxylic acid 10r

• potential and stabilizing the radical pathway. The DFT calculations are shown in Scheme 13A. The activation barrier for the XAT process was calculated to be ΔG‡ = 8.0 kcal/mol, indicating that this process can proceed spontaneously around room temperature. Moreover, the transition state (TS1) suggested the

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

• stereoselectivity, exclusively yielding the Z-isomer. Nonan-2-one required activation with the stronger methanesulfonic acid and gave a 91:9 regioisomeric mixture of 91 to 92. 1-Tetralone provided the corresponding product 61 in only 7% yield; the acid additive was not specified in this case. The authors were

• initiated by the activation of allyl bromide using InCl3 (Scheme 48C) [158]. Very likely the first step involves the generation of allyl cation I by activation of the allyl bromide with InCl3. Subsequent trapping by the appended alkyne will form alkenyl cation II. Cation II then reacts with dichloromethane

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

• of 0.1 V/s at 298 K. Free energy diagram of possible interaction pathways between 1a and dinitramide-derived radical A according to ωB97X-3c [94]/CPCM(MeCN) level of theory. Free energies ΔG and activation free energies ΔG≠ are given in kcal/mol. Dashed lines correspond to spin-state-changing

• -azoxylation of nitrosoalkanes containing electron-withdrawing groups. Synthetic utility and derivatization of synthesized coupling product 2f. Control experiments. Proposed mechanism for electrochemical nitro-NNO-azoxylation of 1-nitro-1-nitroso compounds 1. Free energies ΔG and activation free energies ΔG

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

• gene clusters that code for a (3R) configuration. Keywords: C–H activation; indole alkaloid; Negishi reaction; prenylation; Introduction Alkaloids constitute an important family of naturally occurring compounds with a rich history in the annals of bioactive compounds [1]. Among these, the family of

• alternative approach to C-7 functionalization of Nα-Boc-tryptophan methyl ester, we chose a CH activation protocol [33]. Treatment of N1-Piv-Nα-Boc-tryptophan methyl ester (10) with but-3-en-2-one (MVK) in the presence of [RhCp*Cl2]2 catalyst according to Ma et al. [34] led to the 7-(3-keto-1-butyl)-alkylated

• , the Pirrung group reported two practical syntheses of 7-prenylindole [48][49]. The regioselective C-7 prenylation of indole has been achieved by directing-group C–H activation as reported by Snieckus [50]. However, the deprotection of the preferred N-bis-tert-butylphosphinoyl directing group required

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

• and Figure 3. For chalcones with X = –Cl, –NO2 the activation Gibbs free energies for step Int3 → T.S. → vicinal product (Scheme 4) for the formation of the α,β-ditosyloxy ketones are 12.88 kcal/mol, 13.22 kcal/mol, respectively, while for the formation of the β,β-ditosyloxy ketones, the corresponding

• same is not true when X is an electron-donating group. For X = -OCH3, -SCH3 activation Gibbs free energies for step Int3 → T.S. → vicinal product (Scheme 4) leading to formation of α,β-ditosyloxy ketones are 14.40 kcal/mol, 16.01 kcal/mol, respectively, while in case of the formation of β,β-ditosyloxy

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

• , with the hydroxy group at C17 playing a crucial role trapping a cationic intermediate from this rearrangement. Starting point in this synthesis is again dehydroepiandrosterone (24), which was protected in 3-position with an acetyl group (Scheme 12). A copper-mediated C–H activation procedure to obtain

• the semisynthesis of Liu/Qin [26] 15 years later. The only non-green transformations displayed at the start were a protecting group installation (red) and a condensation (yellow), which was needed for the C–H activation (light green). All other transformations connect either C–C or C–heteroatom bonds

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

• ]. The use of visible light as an energy source has significantly expanded the scope of organic molecule activation and its application in organic synthesis or medicinal chemistry [12], thereby driving the fast development of various photocatalytic transformations. Among these advances, dual catalysis

• process, such as being environmentally friendly, offering operational simplicity, lower cost, and easy availability, reducing waste and toxicity, as well as providing excellent chemo-, regio-, and enantioselectivity through fine-tuned hydrogen bonding or covalent activation modes. Furthermore, the

• silylboronates 13. This photochemical method operates via catalytic activation of the silylboronate 13 in the presence of NHC (10 mol %) and 4CZIPN (1 mol %) with Rb2CO3 (10 mol %) as a base in CH3CN at rt for 20 h. The approach affords highly functionalized β-silylated aryl ketones 14 in moderate to good yields

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

• , provided carboxylic acid 113 in a single operation. Subsequent activation of 113 with acetic anhydride, relactonization, and organoselenium-mediated regioselective epoxide opening yielded mono-enone 114, successfully installing the key C9 and C10 chiral centers with the required oxidation states. Notably

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• photochemical process occurs, which triggers the release from only the vesicles containing EYPC. These findings underscore the significance of both the physical and chemical properties of the bilayer in enabling effective light-triggered cargo release through rotaxane activation. Keywords: lipid membrane

• bacteria or malignant cells like cancer) [5][6], or to influence membrane protein function and thereby control cellular behavior [7][8]. One promising approach is the development of light-activated molecules that can modulate membrane properties upon irradiation, enabling remote activation with high

• light activation of axle 3. Lastly, in LUVs composed of DPPC, irradiation of rotaxane 1 resulted in a total sulforhodamine B release of 14%, representing an increase compared to the minimal release observed under non-irradiated conditions (3–7%) (Table 1 and Figure 6). In contrast, irradiation of

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

• valuable platform for the selective functionalization of carbazoles, offering potential applications in optoelectronics, functional organic materials, and related areas while contributing to the advancement of C–H activation methodologies. Keywords: C–H activation; carbazole; catalysis; nitration

• addition to cross-coupling reactions, transition metal-catalyzed cyclization involving C–H activation approaches have also been reported [29][30][31][32][33][34][35][36]. Despite the significant advances in carbazole core constructions, the established protocols significantly lack access to selectively C1

• -decorated carbazoles. Consequently, functionalizing carbazoles via transition metal-catalyzed directed C–H activation becomes more attractive to introduce the desired functionality in a regioselective fashion. The C–H activation strategy is elegant in many ways since it utilizes nonfunctionalized or lesser

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• the N atom is positioned antiperiplanar to the adjacent C19–C3 bond, an intermediate IN4 with a bicyclo[2.2.0]hexane unit was successfully located. However, the Gibbs free energy of IN4 (ΔG° = +27.4 kcal/mol) is significantly higher than the activation energy of TS2 (ΔG‡ = 22.4 kcal/mol). This energy

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• axially chiral selenium-containing compounds by the formation of C–Se bonds is reviewed from three aspects. Review 1. Catalytic atroposelective synthesis of selenium-containing atropisomers by transition-metal-catalyzed C–H selenylation reactions Transition-metal-catalyzed enantioselective C–H activation

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

• ring contraction reaction on simple cyclohexanones to synthesize functionalized di- and triquinanes [51]. Treatment of 6-oxabicyclo[3.2.1]octan-8-one 86 with BF3·Et2O (2 equiv) promoted the activation of the carbonyl group in 87 by the Lewis acid, leading to the formation of an oxocarbenium ion 88

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• this key intermediate in hand, β-hydroxy acid 29 was synthesized through deprotection, IBX oxidation, and Pinnick–Lindgren–Kraus oxidation and the β-lactone 13 was subsequently obtained through activation of the carboxylic acid. Although we successfully constructed the molecular scaffold of

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• the macrocycle interaction with the axle. In a different approach, the authors demonstrated that the macrocycle can shuttle along an axle by incorporating two acridane photoswitches at both ends. However, upon light activation, the macrocycle stops shuttling and remains in the middle of the axle

• authors successfully prepared the corresponding pseudorotaxane (lacking stopper groups), which underwent dethreading upon light activation, demonstrating the potential of acridane-based macrocycles for light-controlled mechanical motion in rotaxanes. Anthracene Hirose and co-workers developed [2]rotaxanes

• surrounding environment. Controlling macrocycle shuttling via light activation has proven valuable for enabling secondary functions. For example, when integrated into polymers or gels, the mechanical motion of rotaxanes can be harnessed to control the macroscopic properties of materials or even generate