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

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• novel inherently chiral ligands have been explored. For example, they demonstrated excellent enantioselectivity control in some asymmetric reactions, such as the Rh/diphosphine ligand 66-catalyzed asymmetric addition reaction between cyclic enone and arylboronic acid. In 2024, our group reported the

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• –guest complexation realizes a reversible ON-OFF-ON type pseudo-monomeric ligand-gated ion transport switch [91]. The development of these pillararene-based materials has enriched the dynamic regulation methods of supramolecular structures and provided innovative approaches for prodrug design. 2 Stimulus

• chiral ligand, which was modified on the upper rim of calixarene through hydrogen bonding. An azobenzene group was introduced as the photo-regulating part at the upper edge of calixarene. The alkyne at the lower edge of FC4AD was used to form self-assembled monolayers (SAMs) on a silicon surface through

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• iodides (Scheme 1a) [27]. This transformation proceeded via two key steps, isocyanide insertion and desymmetric C(sp2)–H bond activation. By using phosphoramidite L1 as the chiral ligand, planar chiral pyridoferrocenes 2 were obtained in 61–99% yield with 72–99% ee. In addition, this catalytic system

• ] between alkynyl ketones 33 and isocyanoacetates (Scheme 6) [38]. The success of this study not only adds a new entry to the de novo arene formation strategy [39][40] but also initiates the application of isocyanoacetates in constructing axial chirality. With Ag2O and quinine-derived amino-phosphine ligand

• 34f could be used as the starting material to prepare the axially chiral olefin-oxazole 37, which might be a potentially useful ligand in asymmetric catalysis. A possible stereochemical model was proposed as well, involving synergistic activation of both the alkynyl ketone and isocyanoacetate by the

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

• ; photochemistry; Soon after its first reported synthesis in 1936 [1], [Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine) and its derivatives attracted significant attention due to their photophysical properties [2][3][4]. These complexes can efficiently absorb visible light through a metal-to-ligand charge transfer (MLCT

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• widely distributed nuclear receptor proteins and include two subtypes, ERα [3][4] and ERβ [5][6]. These receptors can bind 17β-estradiol with similar affinity, facilitating the transfer of estrogen to various tissues in the body. Due to this, 17β-estradiol as non-selective ligand has been extensively

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• values. Our calculations show that, as expected, 12-crown-4 16a and 15-crown-5 16b are too small and consequently the barium cation lies outside the average molecular plane determined by the macrocycle. In the case of 18-crown-6 16c, the cyclic ligand accommodates very well the cation, which is now

• within the average molecular plane. In addition, the corresponding ΔGiso values increase with the n-values (Figure 4A). Ligand 21-crown-7 15d suggests that this size of the cyclic ligand is less than optimal, since the calculated structure shown a concave-convex topology, in which one oxygen atom

• , highlighted by an asterisk, lies out from the direct coordination perimeter, thus suggesting that this ligand is too big. The relatively lower increase of the ΔGiso(d) with respect to its ΔGiso(c) congener also indicate that the stabilization induced by the additional oxygen atom is lower in magnitude. An

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• , very recently it was found that the C≡P moiety, in particular, can be stabilized in the form of a cyaphide ligand bonded to a metal fragment [99][100]. These cyaphide complexes are proven to readily undergo 1,3-dipolar cycloaddition reactions with organic azides [99][100][101], affording novel metal

• interaction derives from both electrostatic and orbital interactions, which are markedly more stabilizing for the process involving the magnesium cyaphide complex. The stronger electrostatic interactions mainly result from the significant polarization of the cyaphide ligand induced by the highly

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• carried out by using 3-bromochromone (7a) and morpholine (8a) as model substrates in the presence of Ni(II) salt (5 mol %) and ligand (5 mol %), a pyridinium salt (1 equiv) and a photocatalyst (1 mol %) under 427 nm blue LEDs. After carefully screening of the reaction parameters (Table 1 and Tables S1–S7

• -dimethylformamide (DMF) at 20 °C afforded the best results, giving the desired product 9a in 70% isolated yield (Table 1, entry 1). Changing NiBr2·diglyme to other nickel salts, such as Ni(OTf)2 and NiCl2·diglyme led to lower yields (Table 1, entries 2 and 3). Similarly, changing the ligand for dtbbpy or

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• substitution reactions [1]. In particular, the authors elaborate the concept and recent developments in this field, which allows access to enantioenriched chiral enynes. Interestingly, the article also illustrates the effects of the copper salt and the ligand employed, as well as the influence of the substrate

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• without the aminopropyl ligand. Under these conditions, only 48% of the product was obtained (Table 3, entry 13). This result demonstrates that the activity of the Cu catalyst is significantly influenced by the surrounding ligands. The amino ligand not only stabilises the catalyst, by ensuring stronger

• in the preparation (theoretical loading). This suggests that optimum catalyst distribution and activity is achieved with 5 wt % supported CuCl. The two catalysts were also characterised by FTIR and DR UV–vis spectroscopy, to obtain information about the grafted aminopropyl ligand and inserted copper

• functionality, respectively. Figure 5 shows the FTIR spectra measured on the silica support functionalised with the aminopropyl group, and the subsequent insertion of copper. The successful grafting of the amino ligand is testified by the characteristic stretching and bending modes of the NH2 group (νNH2 and

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

• ) [48]. Good yields were obtained only when CuI was used in combination with 1,10-phenanthroline as a ligand, and this intramolecular Ullmann-type coupling was found to be compatible with primary, secondary and tertiary alcohols, with secondary alcohols exhibiting the following order of reactivity

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• heteroatom for the synthesis of functionalized oxindoles was also reported in 2013 [3]. In this study, DBU was employed as a ligand and TBHP as an oxidant. A series of ethers, including 1,2-dimethoxyethane, THF, 1,4-dioxane, tetrahydro-2H-pyran, 2,3-dihydrobenzofuran, tetrahydro-2H-thiopyran, and N

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I