Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• important in pharmaceuticals, catalysts, and advanced materials due to their unique stereogenic scaffolds and associated properties. Consequently, synthetic chemists have been pursuing molecules featuring these forms of non-central chirality, where the stereogenic elements are not localized on a single

• within three-dimensional molecular frameworks that restrict conformational freedom. The geometric scaffolds can be a central atom, an axis, or a plane, and the combination and spatial arrangement of chemically distinct substituents establish the stereogenicity. Therefore, despite the apparent differences

• among these scaffolds, the various types of chirality are permutations of substituents on diverse stereogenic elements (Scheme 1C). Although this analysis offers a unified view of chirality, the realization of these chiral systems through asymmetric synthesis is far from trivial. Stereogenic compounds

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• Collins and Stuart Warriner for their support and assistance in this work. This work is based on the doctoral theses of Scott Rice (“Synthesis of Novel Polyfunctional 3D Scaffolds for Drug Discovery”, University of Leeds, 2021) and Julian Chesti (“Modular Synthesis and Biological Evaluation of

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

• 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

• framework of the diol precursors, predominantly axially chiral structures such as BINOL, H8-BINOL, SPINOL and VAPOL scaffolds, which are widely used in the development of CPA catalysts. Furthermore, the ortho-aryl substitutions of the CPA catalyst can efficiently modulate the stereochemical and electronic

• 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

• synthesis of helically chiral, planarly chiral and inherently chiral molecules. General structure of CPAs and selected CPAs with various chiral scaffolds. Representative elements of molecular chirality. CPA-catalyzed asymmetric synthesis of azahelicenes via Fischer indole synthesis. CPA-catalyzed asymmetric

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• functional groups are isolated together in confined space [7][8][9]. In the solid state, the generation of such multifunctional cavities has been pursued upon nanoporous scaffolds that include polymers of intrinsic microporosity (PIMs) [10][11][12][13], mesoporous silica materials (MSMs) [14][15][16][17

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• hypothesis, we commenced our investigation by employing arylamine 1a and styrene (2a) as model substrates. The optimized reaction conditions are presented in Table 1. Building upon our previous studies, where we investigated how solvent selection can influence the selective formation of quinoline scaffolds

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• would be of help in further drug design of spirocyclic scaffolds. Single crystal X-ray analysis for the compounds 6e (A), 7d (B), 8e (C) and 9e (D). Atoms are shown as thermal ellipsoids at 50% probability. All hydrogen atoms, except the one at the stereogenic center, are omitted for clarity. Synthetic

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

• -promoted glycosylation reactions with α-lactol acceptors 176 and 178, respectively [123]. These nonreducing disaccharides were employed as scaffolds for the synthesis of immunomodulatory glycolipids – TLR4 agonists with picomolar potency [124]. Conclusion Approaches to 1,1'-glycosylation can be rationally

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

• of structurally diverse scaffolds featuring axial, planar, helical, and inherent chirality. Herein, we summarize the exciting achievements in this rapidly evolving field. These elegant examples have been organized and presented based on the reaction type as well as the resulting chirality form

• attention due to its broad applications in various fields, including but not limited to drug discovery, asymmetric catalysis, and materials science (Figure 1b). Consequently, the development of efficient and stereoselective methods for assembling such scaffolds with respect to structural diversity has

• cyclization of functionalized phenyl isocyanides, guided by DFT calculations (Scheme 2b) [29]. Three types of isocyanides (10–12) were evaluated in reactions with aryl iodides, affording indole-fused N-heteroaryl scaffolds 13–15, featuring either a C–C or C–N stereogenic axis, in moderate-to-high yields with

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• enzymatic terpene cyclization and chemical synthesis [30][31][32][33]. Briefly, the carbon scaffolds are forged by terpene cyclases, followed by concise chemical transformations to yield the desired natural products. Here, we describe heterologous biosynthesis of cotylenol by engineering the biosynthetic

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

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• versatile scaffolds for chiral optoelectronic applications. The incorporation of nitrogen enables precise modulation of electronic structures, redox characteristics, and intermolecular interactions, thereby enhancing performance in circularly polarized luminescence (CPL), thermally activated delayed

• (MR-TADF) emitters to date. In 2023, the same group introduced the first deep-blue chiral MR-TADF emitters based on heterohelicene scaffolds 41a–c [56]. These compounds exhibited sharp emissions at 440–444 nm in solution and 445–449 nm in doped films, with emission bandwidths as narrow as 23 nm and

• [5]helicene (compound 57b) by coupling two 12H-benzo[b]phenoxazine (BPO) units and systematically compared it to its N,N-analogue (compound 57a) derived from 13H-dibenzo[b,i]phenoxazine (DBPO) scaffolds [72] (Table 19). Compound 57b was obtained in significantly higher yield and, like compound 57a

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• conducting polymers or scaffolds for drug synthesis. Among them, 1,3-dihydrobenzimidazoles are widely found in many materials, drug candidates, and catalysts. For instance, they can be used in organic light-emitting diodes (OLEDs) [38], as water-soluble antitrypanosomatid agents [39], or in the synthesis of

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• design beyond all-hexagon polycyclic aromatic hydrocarbons (PAHs). Among these, π-conjugated scaffolds featuring embedded azulene units have gained considerable attention due to their unique optical and electronic properties. This review provides an overview of representative azulene-embedded

• gap, aromaticity of azulene subunit and anti-Kasha’s emission from higher excited states. In such cases, the azulene unit merely acts as a linker within a more complex benzenoid framework. This review covers all types of azulene-embedded molecular scaffolds, regardless of whether they contain a

• scaffolds of this type. Given the rapid progress in this field, with nearly half of the cited works published since 2020, this review focuses primarily on purely hydrocarbon structures, with less emphasis on heteroatom-containing molecules. Typically, only the final synthetic steps leading to the fused

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

• difunctionalization of N-arylacrylamides has emerged as a powerful strategy for the construction of diverse nitrogen-containing heterocycles, particularly oxindoles and related scaffolds. This review provides a comprehensive summary of recent advances in oxidative radical difunctionalization of N-arylacrylamides with

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• modifications of MCRs could generate novel and complex molecular scaffolds [1][2][3][4][5][6][7][8]. Some MCR adducts generated from Ugi, Passerini, Gewald, Biginelli, and Groebke–Blackburn–Bienaymé (GBB) reactions have been modified to form chemically diverse heterocyclic scaffolds with potential biological

• activities [9][10]. Imidazo[1,2-a]pyridine and isoquinolinone-kind scaffolds are privileged rings which can be found in drug molecules such as zolimidine [11], zolpidem [12], alpidem and antiemetic drug 5-HT3A antagonist palonosetron [13] (Figure 1). Imidazopyridine-fused isoquinolinones have been developed

• group on the imidazopyridine moiety have direct electronic impact on the IMDA reaction. This integrated reaction process provided a new avenue for the preparation of heterocyclic scaffolds with potential biological activity. Experimental General procedure for the synthesis of intermediates 4 and 6 The

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• (MMV) [3]. OSM’s aim is to “find a drug for malaria as quickly as possible” [3]. In the past, OSM synthesised and screened various derivatives of three related parent scaffolds (series 1–3) provided by GlaxoSmithKline (GSK) in non-commercial antimalarial screening datasets [4]. The group’s current

• et al. for 5-position halogenated scaffolds [10]. Several different triazolopyrazine compounds bearing chlorine, bromine or iodine at the 5-position, gave no ipso-substituted (5-substituted) products when refluxed in toluene with phenethylamine, with all major products being substituted at the 8

• -position (tele-substituted; Figure 1), distant from the halogen leaving group at position 5 [10]. A plausible reaction mechanism was proposed by Korsik et al. [10]. The antimalarial activity of series 4 triazolopyrazine scaffolds is generally reduced by substitution of an amine functionality at the 8

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

• the past five years is presented, particularly emphasizing the active scaffolds of bioactive cinnamic acid derivatives. The review provides a strategic overview of alternative synthetic routes and highlights the latest innovations, including more efficient, highly selective, and environmentally

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

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• diverse scaffolds have been reported in the literature, the identification and use of novel PCs with tunable and diverse optical and redox properties can pave the way to uncharted reactivity. In this context, sulfur-based cores, widely used as acceptors in photoelectric materials [9][10][11][12][13][14

• : diphenyl sulfone (4), dibenzo[b,d]thiophene 5,5-dioxide (5), and 9,9-dimethyl-9H-thioxanthene 10,10-dioxide (6). The selection of these scaffolds was aimed at investigating the effect of conjugation and rigidity/flexibility on the presence of the same donor (TBA, a). In the case of the D–A compounds 4a and

• transfer (CT) character in scaffolds 4a and 6a can be attributed to the absence of a complete conjugated system. On the other hand, the fluorescence profile showed more differences in the analysis of the three members of the D–A family. Again, 5a revealed a bathochromic effect compared with the less

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• . A preliminary investigation revealed that krishnolide A (7) exhibited unique anti-human immunodeficiency virus (HIV) activity, representing the first report of anti-HIV activity in khayanolide-type limonoids. However, the highly oxygenated and polycyclic scaffolds pose substantial challenges toward

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ) triflate-catalyzed post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds is reported offering high yields (up to 98%) under mild conditions. The synthetic sequence involves the Ugi four-component reaction (U4CR) of pyrazole-3-carbaldehydes, primary amines, 3-substituted propiolic acids, and

• ; pyrazolodiazepines; silver catalysis; Ugi reaction; Introduction Synthetic chemists are continuously involved in the development of methodologies for accessing new heterocyclic scaffolds that resemble naturally occurring products and biologically active molecules [1][2]. Nitrogen heterocycles draw particular

• privileged scaffolds [4][5][6] and are well-known for their use as anxiolytics, hypnotics, and muscle relaxants (Figure 1) [7][8]. Diazepam, sold under the brand name Valium, is among the first marketed medications of the benzodiazepine family [9]. Alprazolam, sold under the brand name Xanax, is a fast

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

• utilizing in situ-generated π-allylpalladium complexes to capture strained cyclic allene intermediates (Scheme 4) [22]. By modulating the ligands in the reaction system, two distinct polycyclic scaffolds, 13 or 14, could be synthesized with high selectivity. Mechanistically, the Pd(0) catalyst coordinates

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• platform for the synthetic diversification on these important scaffolds. Surprisingly, when the TBAF-mediated cyclization was attempted on bisamide 9 the corresponding cyclopropane 18 was not formed (Table 2, entry 6). The use of other mild bases at different temperatures also resulted unproductive

• functionalized cyclopropane scaffolds depending on the nature of the carboxylic acid derivative. Chemodivergent reactivity observed in copper-catalyzed borylative couplings of allylic gem-dichlorides. Cu-Bpin-mediated dimerization of 4,4-dichoro-2-butenoic acid derivatives. Control experiments. Proposed

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

• + 2] cycloaddition established, the scope and pivotal properties of the core structure was assessed (Scheme 1). Single point modifications of the tethered backbone were tolerated, enabling access to small 3D bicyclic scaffolds 4b, 4c, and 4d containing both a boron and ester handle. Consciously aware

• . Access to vicinal boron scaffolds 4f and 4g provided conclusive evidence that sensitization of alkenylboronic esters is achievable using xanthone, with in situ oxidation enabling direct access to otherwise challenging to synthesize cyclobutyldiols. The lower observed diastereoselectivity may reflect

• strategies for cyclobutyl scaffolds [53][54][55], products 6 and 7 could be synthesized via mild conditions [68]. Inspired by recent advances by Nolan and co-workers demonstrating the synthetic power of gold catalysts in EnT catalysis [31][69][70][71][72], we probed the reactivity of [Au(SIPr)(Cbz)] in our