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

• systems – has granted access to increasingly complex helicene frameworks with well-defined chirality. This review systematically summarizes recent advancements in the synthesis, structural engineering, and chiroptical performance of nitrogen-doped helicenes and their heteroatom-doped derivatives

• [33] and Ishigaki’s [34] groups independently reported a class of highly twisted nitrogen-doped heptalene derivatives (e.g., compound 20a), which exhibit consistent absorption at 315 nm and blue fluorescence centered near 450 nm, regardless of the substituents. These compounds display redox and

• , Tanaka’s group synthesized benzannulated double aza[9]helicene 32a and its alkylated derivatives 32b and 32c via a one-pot oxidative fusion strategy [46]. Compared to the parent compound 32a (ΦF = 0.07), compounds 32b and 32c exhibit significantly enhanced ΦF (0.35), red-shifted absorption bands, and |gabs

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• ESIPT exists along with the cis/trans isomerization, creating a rather complicated interplay between two competitive processes. Experimental [49][75][76][77][78][79][80] and theoretical [81][82][83][84] studies of compound 3 and derivatives clearly indicate the excited-state competition between the

• and excited state) were optimized without restrictions, using tight optimization criteria and an ultrafine grid in the computation of two-electron integrals and their derivatives. The true minima were verified by performing frequency calculations in the corresponding environment. The implicit

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• human system. In this study, we isolated two previously undescribed N-salicyl-amino acids as natural products (1 and 2) and other two new derivatives (3 and 4) from the organic extract of a culture broth in a modified starch–glucose–glycerol (SGG) medium of Pseudomonas sp. UIAU-6B. The structure of the

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

• protocol was even applied in the elegant syntheses of platencin [30], and steroid derivatives [31]. Despite these encouraging applications, there is a broad area to be developed for the advancement of green synthesis efforts. Continuing our program on developing environmentally benign synthetic methods [32

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

• epoxides and heteroatom-stabilised carbocations generated from alkenes (Scheme 10). In 1992, Arjona and co-workers examined the synthesis of 4,7-dioxatricyclo[3.2.1.03,6]octane derivatives 45 via intramolecular cyclisation of the corresponding hydroxyalkene precursors 44 using arylsulphenyl and arylselenyl

• electrophilicity of the carbonyl [74]. The oxetane products were obtained in good to high yields and further transformed into useful sulphone, butenolide and tetrahydrofuran derivatives. Besides laboratory-scale reactions, this ring expansion has also found applications in industry, specifically for a multi

• approach to these derivatives can proceed through functionalisations of readily available oxetane-containing building blocks. The most versatile precursor of these building blocks is 3-oxetanone (133) which was first recognised by Carreira and colleagues (Scheme 34). Besides describing its possible

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

• formation of two tropylium fragments within a single molecule. Additionally, they exhibit typical azulene-like optical absorption and the aromatic properties characteristic of azulene subunits. Liu and co-workers extended this chemistry to substituted naphthalene derivatives which led to chrysene fused with

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

• –g), further demonstrating the method’s versatility. Furthermore, a range of isocyanide derivatives, encompassing primary, secondary, and tertiary aliphatic isocyanides, demonstrated compatibility by producing the desired oxindoles 19h–j with moderate to good yields. To investigate the reaction

• radical then reacts with acrylamide to yield the desired product 37. As shown in Scheme 21, a visible light-induced trifluoromethylation/arylation using Umemoto’s reagent for the synthesis of trifluoromethylated oxindole derivatives was reported by Huang and Zhang’s group in 2021 [13]. This method is

• %. Heteroaryl and aliphatic sulfoxonium ylides also participated in the reaction, though with slightly lower yields of product 76f–h. Furthermore, the scope was extended to other N-arylacrylamide derivatives, affording products 76i and 76j with yields of 50% and 90%, respectively. As shown in Scheme 36, the

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• ; condensation; Einhorn-type acylation; 2-methyl N-benzyl benzothiazolium salts; Introduction Aroyl-S,N-ketene acetals, in particular N-benzyl derivatives 1, are very short donor–acceptor chromophores that have recently found a renaissance due to their peculiar intense solid-state emission and significant turn

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

• substitution pattern in the aryl ring does not have a significant effect on the yield of 3 for both acceptor and donor derivatives, which shows the versatility of the developed protocol. However, among halogen-containing derivatives, higher yields were observed for bromine-substituted ones (products 3i and 3l

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• hurdles, this work advocates for a fragment-focused approach as a crucial step toward advancing borrelidin research and expanding its potential applications. Keywords: borrelidin analogs; borrelidin derivatives; borrelidin fragments; borrelidin synthesis; fragment-based synthesis; Introduction

• a marine or hypersaline environment natural products library to identify potent drugs, a putatively novel metabolite co-produced with borrelidin was discovered, expanding the potential for new borrelidin derivatives. This led to the formation of the so-called “borrelidin family” (Table 1), with

• derivatives named alphabetically starting from the original borrelidin 1, designated as borrelidin A (Table 1, entry 1). A rare nitrile moiety at C12 of the macrolide ring in borrelidin A is present in most members of the borrelidin family (Table 1, entries 4, 5, 7–11, 13–16, and 18), except for borrelidin B

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

• ]pyrazine (hereafter referred to as “triazolopyrazine”) analogues, including derivatives inherited from Pfizer and newly synthesised analogues [5]. Triazolopyrazine compounds of OSM series 4 are believed to dysregulate P. falciparum ATP4ase (PfATP4), possibly as a direct inhibitor [5]. Series 4 compounds

• good yield with this straightforward methodology (and without the need for toluene reflux), and to determine the distribution of products obtained for this synthetic approach, by exhaustive analysis of reaction mixtures by HPLC, MS and NMR. Ultimately, 14 aminated derivatives of 5-chloro-3-(4

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• , thus confirming a strong interaction affinity lying within the 104 molar range. Gold extraction with β-CD and derivatives The possibility of using β-CD instead of α-CD in gold recovery and extraction is highly sought after by both researchers and industry because of the readiness of availability of β

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• . It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new and improved way to generate enantiomerically pure pipecolic acid derivatives with

• -inducing properties in peptides [22][23][24]. Furthermore, derivatives of pipecolic acid are known for their bioactivity as secondary metabolites [25][26][27] and for being building blocks for piperidine alkaloids [28] with a variety of uses. Results and Discussion Addressing specific positions in the ring

• a key intermediate product. This late-stage approach was previously described by us while utilising Suzuki–Miyaura or Sonogashira–Hagihara cross-coupling reactions to generate pipecolic acid derivatives with alkynyl substituents in the C6 position [35]. Here, we present a robust synthetic route to

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

• moieties of biologically active compounds. A salen–scandium triflate complex-catalyzed asymmetric (3 + 2) annulation of dialkyl 1-sulfonylaziridine-2,2-dicarboxylates and aldehydes generated optically active functionalized oxazolidine derivatives in moderate to good yields and good to excellent

• enantioselectivities and high diastereoselectivities. A reasonable reaction mechanism was proposed and rationalized the experimental results. Keywords: aldehyde; annulation; aziridine; oxazolidine; ring expansion; scandium triflate; Introduction Oxazolidine derivatives are an important class of nitrogen and oxygen

• [5] and the FDA-approved antibiotic linezolid [6] (Figure 1). Both chiral oxazolidines [7][8] and oxazolidinones [9][10] have been utilized as chiral auxiliary groups in many asymmetric organic transformations. Oxazolidine derivatives have been prepared mainly from condensation of vicinal amino

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

• Cinnamic acid derivatives represent a significant class of biologically active compounds exhibiting a broad spectrum of activities, such as antifungal, antidengue, antimetastatic, antimicrobial, antibacterial, and anticancer properties. Their preparation has attracted considerable attention due to their

• versatile applications across the pharmaceutical, food, and chemical sectors. This review elucidates the functional groups of cinnamic acid that are instrumental in the rational design of biologically active derivatives. A comprehensive representative of recent advancements in synthetic methodologies over

• 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

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• photoreductants, and we considered triarylsulfonium salts Ar3S+X− as suitable probes. Such derivatives are photoreactive molecules characterized by a positively charged sulfur atom bonded to three aromatic moieties [20][21][22][23], mainly employed as photoacid generators in cationic polymerization [19]. Apart

• (whose EREDonset value were in the range −1.60 and −1.92 V vs Ag/AgCl, a set comparable to that reported in the literature for fac-Ir(ppy) [37], which was effectively used in the photoredox-catalyzed reduction of sulfonium salts [29]) and derivatives 1a–d (EAr3S+/Ar3S• = −1.35 to −1.46 V vs Ag/AgCl; see

• + species, a process where transition-metal-based complexes are employed [29], often (in the case of Ru(II)-based derivatives) in the presence of tertiary amines as sacrificial reductants [27][28]. Nonetheless, while this work serves primarily as a preliminary study comparing the reducing power of various

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

• asymmetric allylic amination of allylic esters with isatin derivatives 11 as nucleophiles. The reaction proceeds efficiently, yielding the products (S)-13 with good-to-high enantioselectivity. A scale-up reaction was also successfully conducted at a 1 mmol scale. Additionally, when malononitrile was added to

• Isatin is a well-known natural indole derivative. Due to the broad biological activities of its derivatives, extensive research has been conducted on their synthesis. Furthermore, the isatin framework is a versatile starting material for various transformations, including multicomponent reactions and the

• 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

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

• life on Earth. The importance of these heteroaromatic derivatives has stimulated tremendous investigation towards the understanding of genetic information transmission as well as the synthesis of novel derivatives for medicinal applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. For

• pyrrolopyrimidine derivatives. The envisioned methodology combines a Sonogashira–Hagihara reaction and a one-pot process comprising a Buchwald–Hartwig coupling reaction followed by a hydroamination [23][24]. Results and Discussion The bromination of 6-chloro-1,3-dimethyluracil (1) afforded, following a known

• procedure [25], 5-bromo-6-chloro-1,3-dimethyluracil (2) in 52% yield (Scheme 1). We previously reported Sonogashira reactions of the latter with various alkynes to give products 3a–d,g,h [26][27]. In this work, we extended the scope and prepared novel derivatives 3e and 3f. A nearly quantitative yield was

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• intermediate would meet challenges associated with the instability of enolate derivatives. In their recent study, they successfully developed such a polycyclization taking advantage of a novel spiropyrroline-derived oxazole (SPDO) ligand (L3). As shown in Scheme 7, one-pot condensation of primary amine 40, β

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

• radicals has seen new impetus during the last decade, stimulated by the development of highly efficient electroluminescent devices based on donor-functionalized TTM radicals [7][8][9][10][11][12][13]. Today, new derivatives of donor-functionalized triarylmethyl radicals are being synthesized with enhanced

• demonstration of LEDs with 100% internal quantum efficiency [8][12]. Modern approaches also incorporate light-emitting TTM radical derivatives into LEDs based on thermally activated delayed fluorescence to moderate excited triplet, doublet, and singlet states in an attempt to improve the overall device and

• to be altered sufficiently to evoke a noticeable improvement of the ϕ [48]. This also holds true for mono-para-substitution with boronic acid derivatives, yielding λem = 580 nm and ϕ of 1–3% (in dichloromethane) [49]. Substituting one or two of the 2,4,6-trichlorinated rings in TTM with 2,4,6

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• reactions: reduction of ring A of the β-carboline skeleton or trifluoroethylation of the pyrrole moiety occurred, leading to interesting and potentially useful derivatives. Keywords: alkaloid; β-carboline; Carex brevicollis DC; cross-coupling reaction; trifluoroethylation; Introduction Carex brevicollis

• 21 under extremely harsh conditions (100 °C, 130 bar), followed by N-acetylation gave a mixture of diastereomeric racemates 22, which was cyclized to a diastereomeric mixture of β-carboline derivatives 23. Heating of 23 in pivalic acid in the presence of a catalytic amount of trifluoroacetic acid

• , further investigation is needed to prove this observation. However, the mentioned alkaloids have high potential as medications. Based on the above, research on the total synthesis of these alkaloids and their closely related derivatives is crucial for further confirming their structure and for ensuring

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

• previously reported by Zysman-Colman and co-workers [19]. Compound 5d showed the best performance with a 27% calculated NMR yield (20%, isolated yield) (Table 3, entry 3), while the azepine derivatives 5a and 5b led the transformation at 13 and 8%, respectively (Table 3, entries 1 and 2). However, these

• properties in addition to the previously reported characteristics like highly twisted structures that can be useful in designing new PCs with TADF behavior. We hope this study inspires the construction of new PCs that could combine azepine derivatives, exemplifying the valuable incorporation of widely used

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

• account chemical and pharmacological importance of fused pyrazole derivatives [48][49][50][51][52][53], we herein report the post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds 16 (Scheme 1d). The synthetic sequence involves an Ugi reaction of pyrazole-3-carbaldehydes 14, primary amines 2

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

• hydrogen atom transfer (HAT)/chiral copper dual catalytic system that achieved regiodivergent and enantioselective C(sp3)–C(sp3) and C(sp3)–N oxidative cross-couplings between N-arylglycine ester/amide derivatives and abundant hydrocarbon C(sp3)–H feedstocks (Scheme 6) [24]. This methodology also

• influence of steric and electronic effects during the hydrometallation process, simultaneously achieving the synthesis of chiral α-quaternary carbon amino acid derivatives 26 and α-chiral β-amino acid derivatives 27. Using a copper catalyst, the chiral α-quaternary carbon amino acid derivatives 26 were

• obtained with exclusive regioselectivity and excellent enantioselectivity. Employing a nickel catalyst, α-chiral β-amino acid derivatives 27 were synthesized with single regioselectivity and outstanding enantioselectivity. In the same year, Rong and co-workers reported a highly efficient catalyst

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

• Patricia Gomez-Roibas Andrea Chaves-Pouso Martin Fananas-Mastral Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain 10.3762/bjoc.21.71 Abstract 4,4-Dichloro-2-butenoic acid derivatives

• versatile building blocks for the stereoselective synthesis of chlorocyclopropanes. Keywords: chlorocyclopropanes; copper; cyclization; 4,4-dichloro-2-butenoic acid derivatives; dimerization; Introduction In the last years our group has been focused on the development of catalytic methodologies for the

• reaction was carried out under standard conditions with ethyl crotonate derivatives bearing a methyl group, hydrogen or bromine atoms at the γ position. Either β-borylation or decomposition products were obtained in those cases (Scheme 3c). On the basis of our experimental results, we propose the following