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

• distinct mechanistic pathways, a simplified version of which is described herein. The active catalytic species, palladium(II) pivalate, is formed in situ from Pd(COD)Cl₂ through ligand exchange with pivalic acid (PivOH). Complexation of this active Pd(II) species with ligand L1 and the amide substrate

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

• ][41]. They contain an iron-protoporphyrin core with a cysteine ligand [42] in the axial position, which cycles through different oxidation states (Fe3+/Fe2+/Fe4+) to form highly reactive oxo species which are effective at abstracting closely positioned aliphatic hydrogens via HAT (hydrogen atom

• included [48][49]. These enzymes exhibit distinctly different Fe-containing active sites, typically consisting of two histidines, a carboxylate ligand (e.g., aspartate) and, of course, the ketoglutarate which is bound both via the C-2 ketone and C-1 carboxylate to form 1 (Scheme 1C). Upon its coordination

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

• and nucleotide, DNaze I-binding). The structure of the 8DNH protein was retrieved from the protein data bank and the Molegro Virtual Docker 6.0 software was used to prepare it for the docking study [66][67]. The pose organizer and the ligand energy inspector tool were used to examine the docking

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

• Taube reported the now famous pentaammineosmium(II) η2-benzene complex: the first system to yield kinetically stable η2-arene complexes that resist ligand exchange at room temperature in solution (Figure 5) [48]. This breakthrough opened the door to the isolation of such complexes and their subsequent

• exposure to reaction conditions that more labile systems could not tolerate. Crucially, most reagents used in organic synthesis react preferentially with the arene ligand rather than the metal center [45]. Building on the electronic blueprint established by the osmium system, Harman introduced a new

• , display remarkable substitution inertness, even toward strong π-acids and good σ-donors. The substitution rate being relatively independent of the incoming ligand is consistent with a dissociative substitution mechanism. Typically, coordination occurs at positions that minimally disrupt the arene π-system

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• intrinsic stereoelectronic preferences but also by intermolecular interactions within the ornithine decarboxylase active site. Therefore, the conformational behavior of DFMO arises from a delicate balance between the fluorine gauche effect and the intermolecular interactions that stabilize the ligand–enzyme

• decarboxylase from Leishmania infantum complexed with PLP and DFMO, the bound ligand corresponds instead to human arginase I (PDB code 3GN0). While binding to arginase I is not related to DFMO’s pharmacological activity, both enzymes recognize ornithine-related substrates, allowing DFMO to occupy the arginase

• amino acid residues and water molecules, while the ligand is delineated by a contour line to distinguish it from the binding cavity. Lowest-energy type-I, type-II, and type-III conformers of the zwitterionic form of (S)-DFMO. Color labels: H = blue, C = pink, N = orange, O = red, F = yellow. DFT

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

• [5]helicenes. Scale-up synthesis and post-synthetic application of chiral helical product 8g. Post-synthetic transformation of product 8g to chiral phosphine ligand 12 and its application in Pd-catalyzed reactions. Acknowledgements The authors acknowledge the CSIR-IHBT, Palampur for providing

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

• ], enhancement of cognitive flexibility [9], induction of neuroplasticity in cortical neurons [10], and persistent antidepressant-like effects [11]. Given the widespread use of this ligand in basic research, some scattered data on its physicochemical properties are available, but a structured and comprehensive

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

• chiral platinum(II) complex was synthesized via Sonogashira coupling and subsequent coordination of a pincer ligand to a precursor. The complex exhibited a broad absorption band ranging from 250 to 550 nm in the UV–vis spectrum, with TD-DFT calculations indicating mixed ligand-to-ligand charge transfer

• (LL’CT) and metal-to-ligand charge transfer (MLCT) character. Photoluminescence measurements in CH2Cl2 solution revealed dual emission peaks at 427 nm and 596 nm, with a quantum yield of 3%. In PMMA matrix, the emission peaks were blue-shifted to 408 nm and 558 nm, and the quantum yield slightly

• and synthesis of a chiral ligand featuring an axially chiral binaphthyl backbone and its employment in the construction of novel types of a chiral platinum(II) complex with pincer ligand (Figure 1). We investigated the spectroscopic properties of the resulting complex, including its chiroptical

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

• saturation the aromatic ring facilitates synthetic chemists to efficiently synthesize natural products with complex three-dimensional structures. Recent advances in catalyst and ligand design have enabled unprecedented progress in the catalytic hydrogenation of (hetero)aromatic systems. Quinoline

• both homogeneous and heterogeneous systems, the hydrogenation of (hetero)arenes has become a cornerstone of modern synthesis for constructing saturated carbocycles and heterocycles [37]. When an appropriate ligand is paired with a transition-metal catalyst, stereoselective hydrogenation of aromatic

• catalyst and ligand design showcase complementary solutions to these selectivity issues, with each substrate class imposing its own opportunities on hydrogenation outcomes. With these considerations in mind, the following section categorizes catalytic hydrogenation strategies by arene substrate type and

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

• corresponding vic-bis(dithiane) derivatives 16a–d. In 2018, Milsmann et al. reported the dimerization of benzyl bromide using a zirconium complex as a photosensitizer (Scheme 4) [14]. Heating a zirconium precursor with the pincer-type ligand 17, which can be synthesized in three steps from commercially

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 by a chiral copper complex generated in situ from CuTC and phosphoramidite ligand 361, furnished the corresponding enantioenriched alkenyl chlorides in high yield and with exclusive formation of the Z-isomer. A decade later, Fañanás-Mastral and co-workers demonstrated that alkenylcopper species

• , generated via borocupration of terminal alkynes, underwent allylic substitutions to furnish Bpin-substituted alkenyl chlorides in high enantioselectivity (Scheme 65B) [204]. Key to the transformation was the use of a sulfonate-substituted N-heterocyclic carbene ligand, introduced as its imidazolium salt

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

• methyl ester who observed intramolecular proton transfer with partial incorporation of deuterium upon quenching with deuterium oxide. In a different context, the role of the Pd catalyst and the associated ligand was studied in the cross-coupling of the organozinc reagent ent-35 with 3-iodomethylfuran

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

• enantiomeric excess of 92%. This asymmetric hydrogenation included a novel iridium catalyst featuring a chiral SpiroBAP (spiro bidentate aminophosphorane) ligand, which has been developed previously by this group and was now successfully applied in this synthesis [36]. A silver-catalyzed, enantioselective

• alkyne fragment 116 (see Scheme 33). The synthesis of diyne fragment 112 commenced with an organocatalytic, enantioselective Diels–Alder reaction between siloxydiene 108 (synthesized in one step from ethyl vinyl ketone) and commercially available dienophile 109 using the proline-derived Hayashi ligand

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

• atmosphere significantly suppressed side reactions, yielding the cyclized product in excellent yield and selectivity. This indicates that N-formylsaccharin, beyond acting as a CO-releasing agent, may function as a ligand in the catalytic cycle to regulate the palladium catalyst’s activity and stability

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• . Multiple ligand–receptor interactions can significantly enhance receptor binding affinity and cellular uptake, as well as more effectively modulate signal transduction pathways, for instance when receptor clustering is necessary on the cell membrane [3]. Designing multivalent bioactive compounds thus

• to the nanosize, the calixarene-based nanoconstructs could preferentially accumulate in cancer tissues by exploiting the enhanced tumor permeability and retention (EPR) effect [24] or selectively penetrate cancer cells through specific ligand–receptor interactions on the surface of target cells [25

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

• reinstallation of a single TMS on the alkyne provided pyridyl-alkyne 22 for the second [2 + 2 + 2] cycloaddition reaction which proved nontrivial, with the protecting group on the secondary amine of the alkyne-nitrile moiety and the choice of ligand playing crucial roles. Specifically, when using 19 as the

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

• occurred in an anti fashion. Products were obtained with up to 97% ee via catalysis by complexes of magnesium or copper(II) with ligand L1. The absolute stereochemistry of the product could be controlled by a simple change from copper(II) to magnesium Lewis acids while using the same chiral ligand, thus

• obviating the need for both enantiomers of the ligand. Although chiral Lewis acid-mediated radical reactions were groundbreaking, they suffered from major disadvantages: (a) high catalyst loadings (stoichiometric or sub-stoichiometric), (b) large amounts of the radical initiator, (c) the need for a large

• demonstrated to forge C(sp2)–C(sp2) as well as aliphatic C(sp3)–C(sp3) bonds. The Fu group reported a nickel-catalyzed α-alkylation of racemic secondary α-bromoamides 18 using organozinc reagents 19 (Scheme 4A) [32]. A chiral nickel complex, obtained from the mixture of chiral pyridinebisoxazoline ligand L2

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

• systematically regulating reaction parameters (solvent, substituent, ligand, catalyst) in 1,n-enyne cyclizations, enabling efficient "one-to-many" transformations that drastically reduce synthetic steps and resource consumption. Review Solvent-controlled cyclization of 1,n-enynes Solvents play a multifaceted

• heterocyclic scaffolds, which established a versatile platform for synthesizing structurally diverse indoline frameworks. Ligand-controlled cyclization of 1,n-enynes The core function of catalyst ligands lies in their ability to precisely modulate catalyst performance through electronic and steric effects. The

• nexus for the rational design and optimization of highly effective, selective homogeneous catalytic systems. In 2013, Barriault and co-workers demonstrated that strategic modulation of steric and electronic ligand parameters within gold(I)-catalyzed cyclization pathways enables the selective assembly of

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

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

• optimize the reaction conditions, with particular focus on the choice of ligand, especially for non-ortho-substituted aryl bromides as substrates. Notably, the use of bulkier phosphines, such as P(t-Bu)3 and t-BuXPhos, was found to promote the reaction regardless of the substitution pattern of the

• )–aryl intermediate (B). Subsequently, ligand exchange occurs, generating hydrazido complexes C and C'. When bulky substituents are present on the phosphine ligand and/or (both) coupling partner(s) has ortho-substituent(s), the hydrazido complex C, chelating on the terminal nitrogen, is preferentially

• ) undergoes dehydrogenation via a mechanism involving Pd and O2, similar to the process reported by Huang and co-workers [59]. Initially, Pd(0) species E is oxidized to Pd(II) by O2, forming a Pd-peroxo complex F [60]. Subsequently, ligand exchange occurs between the deprotonated N,N-diarylhydrazine and

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• reversible C–H activation to give the six-membered intermediate C. Substitution of the acetate ligand in C by 3 caused the generation of complex D. The six-membered ruthenacycle E was then obtained by migratory insertion of acetylene into the Ru–C bond. Finally, reductive elimination of E formed the target

• for 6 h. The authors also proposed the reaction mechanism on basis of experimental results and previous literature [205][206]. Firstly, the ligand exchange between (R)-Rh1 and n-Bu4NOAc or 1-AdCO2H gave a chiral active catalyst A. The irreversible base-prompted C–H activation of A with 19a yielded a

• of 22 with Cu(OPiv)2 and the following anodic copper(II) oxidation provided copper(III) carboxylate intermediate B. Facile carboxylate-promoted C–H activation and ligand exchange with 23 formed the copper(III) species D, which underwent metalation/reductive elimination to generate intermediate E

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• for the oxidation of 1,2-diols, triols and tetraols using the chiral palladium-based catalyst 2 bearing a pyridinyl oxazoline (pyOX) ligand (Scheme 31) [110]. 5-Hydroxy-2(5H)-furanone (HFO) 5-Hydroxy-2(5H)-furanone (HFO) is an interesting C4 platform which is formed from furfural by oxidation. Han and

• ligand led to excellent enantioselective induction during the hydrogenation step. Higher H2 pressure could promote the regeneration of Cu–H species [214]. Levulinic acid (LEV) Levulinic acid is a biodegradable C5 carboxylic acid with high potential as a platform chemical in the field of polymers, fuels

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• both in pure form from only one enantiomer of a chiral starting material or a chiral ligand [33]. To demonstrate the value of our protocol in this regard, an enantiodivergent synthesis of isochaetominine (10) was envisioned. Previously, we have reported a four-step synthesis of (+)-isochaetominine (ent

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• (Figure S1 in Supporting Information File 1). The interaction of compounds 7a–c with duplex DNA was then investigated by fluorescence titration, measuring the quenching of ligand fluorescence upon binding to the nucleic acid. Fluorimetric titration studies confirmed the interaction of 7a–c with double

• -stranded calf thymus DNA, as evidenced by ligand fluorescence quenching (Figure 2). Elongation of the linker in the carboxamide residue is accompanied by weaker DNA complexation (Table 4). The interaction of the compounds with DNA was found to be largely dependent on electrostatic forces. Reducing the

• stoichiometry of one ligand per two base pairs at maximal DNA saturation. While the DNA binding affinity increased by an order of magnitude at low ionic strength, the characteristic decrease in affinity with longer linker lengths was still maintained. A similar trend was observed in the results of MTT assay

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• of the product in the same process by employing the antipodal ligand, as both enantiomers of the chiral ligand are normally accessible. Additionally, the substrate scope can be broadened by modifying the ligand’s structure. Early in 1984, Ichikawa and co-workers reported a Sn-mediated

• 139, epoxide 136 was first prepared from (R)-130 in two steps. Parikh–Doering oxidation of 136 followed by addition with Et2Zn in the presence of ligand 137 afforded alcohol 138, which was subsequently converted into amine 139 via a seven-step sequence. With the fragments 135 and 139 in hand

• diol 158, the ligand with only isopropyl substitution at C4 proved effective with suitable size for the substrate–catalyst coordination. A subsequent two-step sequence enabled the sythesis of olefinic carbamate 161 from benzoate 160. Treatment of 161 with Hg(CF3CO2)2 induced mercuriocyclization