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

• reactions, chemists have developed a series of catalysts composed of transition-metal cores and chiral ligands, which have been applied to various asymmetric reactions [50][51][52]. Compared to the enzymatic methods, the transition-metal-catalyzed approach may provide an advantage to access both enantiomers

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

• products, agrochemicals, and pharmacologically active compounds. Enantiomerically pure 1,2-diamines and their derivatives are also increasingly used in stereoselective synthesis, particularly as chiral auxiliaries or as ligands for metal complexes in asymmetric catalysis [1]. Metal-based reductants

• scaffolds that are commonly used as chiral ligands. In this context we report the development of a more sustainable method – which avoids the use of lead bromide or lead electrodes – employing an undivided cell with two glassy carbon electrodes for the electroreductive intramolecular coupling of aromatic

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

• leveraging the synthesized enantioenriched aza[6]helicene 29a and tetrahydro[6]helicene 30a as chiral building blocks, a series of helically chiral organocatalysts and ligands could be easily prepared, such as the helically chiral pyridine N-oxide 31a and helically chiral monophosphine ligands 31b,c, whose

• versatility of this method in the asymmetric synthesis of diverse chiral molecular structures. Substituted [2.2]paracyclophanes represent another class of conformationally rigid, planarly chiral molecules, which have emerged as versatile scaffolds for developing chiral catalysts, ligands and functional

• DDD products 64e. Moreover, the authors showcased the facile derivatization of dimethoxy-substituted chiral DDD 64f into various DDD-based chiral ligands, such as the phosphoramidites 65, phosphoric acid as well as monophosphine ligands and diphosphine ligands 66. Notably, the applications of these

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

• replacing the azobenzene moiety of the already established partial agonist GluAzo with a diazocine unit. While both photochromic ligands show biological activity in the E form, the E-isomer is the thermodynamically more stable one for the azobenzene analog, whereas for the diazocine-modified

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines

• bisoxazolines [1][2][3][4][5][6][7][8][9] and bisimidazolines [10][11][12][13][14][15] are efficient chiral ligands and have been widely applied in various metal-catalyzed asymmetric organic transformations. Various chiral bisoxazoline ligands have been prepared from diacids and enantiopure vicinal amino

• alcohols and utilized in different metal-catalyzed asymmetric organic reactions [1][2][3][4][5][6][7][8][9]. In comparison with bisoxazoline ligands, relatively less attention has been paid to bisimidazoline ligands [10][11][12][13][14][15]. Some well investigated bisimidazoline ligands are pyridine-linked

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

• -affinity host–guest interactions between PA5 and these groups (mainly through phosphonate-quaternary ammonium ion pairing) [90]. Azobenzene guest molecules can achieve dual functions (on and off) as ligands through photo-induced cis-trans isomerization. Using pillar[6]arene as the ion channel, the host

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• others (11–19) (see Figure 1), which may serve as virulence factors [8][9][10][11][12][13]. Most significantly, some of these indoles have been shown to be potent aryl hydrocarbon receptor (AHR) ligands [8][9][14][15], which can lead to induction of melanocyte apoptosis and inhibition of neutrophil

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• , the chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

• = 365 nm. Using this novel approach, α,α-1,1'-linked Gal-Fuc thiodisaccharides, designed as bispecific ligands for the Pseudomonas aeruginosa lectins LecA and LecB, which play key roles in host cell adhesion and exhibit cytotoxic effects, were successfully synthesized [120]. Tetraacetylated α-galactose

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

• identified. While the employment of L9 afforded endo-selective [3 + 2] cycloadducts 60, using Trost ligand L10 resulted in a complete reversal to the exo-cycloadducts 61. DFT calculations were performed and indicated that these two ligands act in different ways in the cyclization process, providing

• chiral products, e.g., biological activities and utility as chiral organocatalysts or ligands, warrants greater attention. We anticipate that considerable efforts in these directions would be crucial for advancing this field and fully unlocking the synthetic potential of isocyanides in the preparation of

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• substituent(s) at appropriate position(s) on the benzene rings [8]. Enantiopure planar chiral [2.2]paracyclophanes have been used as chiral auxiliaries and chiral ligands for transition metals in the fields of organic and organometallic chemistry [9][10][11][12][13][14][15][16][17][18][19][20]. In 2012

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• iodonium salts with common dummy ligands such as 2,4,6-trimethoxyphenyl (TMP) [42][43], sterically hindered 2,4,6-triisopropylphenyl, and mesityl ligands. The highest selectivity was achieved using aryl(2,4,6-trimethoxyphenyl)iodonium triflates 1n–p yielding the desired amides 2ba, 2bo, and 2bp in 25–42

• , which provided the best yields in the scope. Moreover, the strong correlation of the yield with the electronic effects in aryl rings was clearly shown in the experiment with iodonium salt 1q (Scheme 3). We believe that the reason for the predominant transfer of the electron-poor ligands under the given

• transfer of a single aryl group from unsymmetrical diaryliodonium salts was demonstrated through the use of dummy ligands, such as 2,4,6-trimethoxyphenyl. Background and conception. Reaction scope of iodonium salts 1 and isonitriles. aReaction conditions: isonitrile (0.2 mmol), iodonium salt 1 (0.2 mmol

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

• -amination of benzoxazoles by transition-metal-catalysed reactions that traditionally involve aryl halide scaffolds [11][12][13][14]. However, these procedures entail disadvantages that need to be overcome if green chemistry criteria are to be met; high temperatures, long reaction times, the need for ligands

• of azolic substrates, but here the amines and the ligands are still used in excess and auxiliary oxidants are occasionally employed [33][34][35]. Although electrophilic amines, such as chloroamines [36][37], hydroxylamine [38][39][40], acylated hydroxylamine (with a wider reaction scope) [41][42][43

• 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

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• yields of 1,2-thiazoles 3aa–ae are slightly lower (70 vs 78%) than by method A. We also investigated the effect of chiral catalysts or ligands in the reaction of thioamide 1a with 2a; however, we were unable to achieve high enantiomeric purity of product 3aa (see Supporting Information File 1, Table S1

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

• cases and worked very well for both aromatic and aliphatic amides, as well as sterically hindered oxetanes. The authors further proved the robustness of this reaction by preparing various bisoxazolines 189, compounds which are common bidentate ligands in asymmetric catalysis [99]. Over the years 2019

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

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• that this approach does not allow us to predict the occurrence of the reaction, its yield, or confirm if the reaction might proceed via a different mechanism influenced by the substrate, catalyst, and ligands. Second, we assume that the reaction is controlled kinetically, where the activation energy

• simulating different solvent effects or examining the impact of different catalysts and ligands, extending beyond Pd(OAc)2. Additionally, accounting for varying reaction conditions, like conducting the reaction in acidic or basic environments, is possible by adjustments to the substrate-SMILES. Protonation

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• ). Other rare-earth salts, including Y(OTf)3, La(OTf)3, Sm(OTf)3, Tb(OTf)3, Er(OTf)3, and Lu(OTf)3, were also screened, but no better results were observed (Table 1, entries 6–11). In addition, different ligands L2–L4 were evaluated (Table 1, entries 12–14). The enantiomer of product 3aa was obtained in 28

• % yield with 31% ee and >20:1 diastereomeric ratio in the presence of ligand L2 (Table 1, entry 12). However, ligands L3 and L4 were completely inactive. Thus, further optimizations were performed with 10 mol % of Sc(OTf)3 and L1. The reaction was conducted at different temperatures for 12 h for saving

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• product 245 or the corresponding Z-isomeric product 246, both in good yields. Alkenyl sulfides have also been used for the preparation of cinnamic acid esters. For example, Wu and co-workers (2020) studied the Pd-catalyzed carbonylation of alkenyl sulfides in the presence of NHC ligands via C–S cleavage

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• amination of allyl esters using isatin as a nucleophile. In this reaction, bisphosphine-type ligands such as BINAP and SEGPHOS derivatives, as well as P,N-type ligands like oxazoline-type ligands, were utilized as chiral ligands [26]. On the other hand, several groups have recently reported new chiral

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

• chirality, such as N-alkyl-N-cinnamyl-type chiral ligands 4 [28][29] and 5 [30], and a P,olefin-type chiral ligand 6 [31] with a cinnamoyl group instead of a cinnamyl group. In particular, the chiral ligand 6 is effective in the Pd-catalyzed asymmetric allylic substitution reaction of allylic esters with

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• efficient for related transformations [28][29]. However, only a yield of 15% of the desired product 4a was obtained after stirring for 15 hours, due to low conversion of the starting material. Subsequently, different mono- and bidentate ligands were tested. DPEphos was found to be the most potent ligand

• , leading to 43% isolated yield with full conversion of starting material and different byproducts derived from decomposition. Interestingly, no conversion of the starting material could be observed with the other ligands. In the following, different solvents, temperatures and bases were tested, but did not

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• literatures focusing on key regulatory factors for product divergent formation, in which controlling chemical selectivity primarily relies on ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates. To gain a deeper understanding of the mechanisms underlying

• review systematically examines, how these multidimensional control elements (including ligands, metal catalysts, solvents, time, temperature, acids/bases, and subtle modifications of substrates) synergize to achieve predictable product diversification. In addition, mechanistic insights are discussed

• , enabling programmable access to structurally distinct molecular architectures from identical substrate precursors through precise manipulation of metal coordination [16][17][18]. This sophisticated approach capitalizes on the stereoelectronic tunability of ancillary ligands to dictate reaction pathways

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• ). Efficient EnT catalysis could be achieved with neutral trigonal planar systems 1a–d, while BMIDA substrate 1e was also effective presumably due to the proposed hemilabile nature of the MIDA protecting group in acetonitrile [58]. More electron-donating ligands such as 1,8-diaminonaphthalene (BDAN, 1f) were

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• promote this cascade reaction for the synthesis of quinazolinones without the need for additional ligands or additives (Scheme 1a) [7][10]. Since then, various copper-based catalysts, both homogeneous and heterogeneous, have been explored (Scheme 1b) [11][12][13][14][15][16]. For example, Wang’s group

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• well as ADMET properties. All compounds satisfied these criteria, indicating favorable oral bioavailability. Molecular docking analysis showed that compounds 5a–e act as ligands for inducible nitric oxide synthase (iNOS), especially with Cys200 and Ser242 via hydrogen bonds. In addition, van der Waals

• ligands (Figure 4 and Figure 5). Additionally, dexamethasone (DEX) was employed as an experimental control for comparative purposes [34][35][36]. The docking scores (DS), reported in Table 5 as binding affinities, reveal that negative DS values correspond to stronger binding affinities between the ligand

• that all ligands consistently interacted with Cys200 and Ser242, key residues in the enzyme's active site, underscoring their critical role in ligand stabilization. In addition to hydrogen bonding, extensive van der Waals interactions were observed, particularly involving residues such as Thr190