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

• methods for oxetane synthesis, mainly due to its practicality and versatility. 1.1.1.1 Substitution of a leaving group: In 2017, Moody et al. developed a new route towards spiro-oxetanes 8 utilising a combination of 1,4-C–H insertion and Williamson etherification (Scheme 3) [38]. The methodology commences

• derivatisation methods have been developed – these expand not only the scope of synthetic strategies towards known oxetane building blocks, but also the library of medicinally relevant oxetane derivatives. This chapter summarises the recent functionalisations of 3-substituted oxetanes whose synthesis can be

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• modified. In recent years, photocatalysis has been widely adopted due to its green and efficient nature [45][46][47][48][49][50][51]. The generation of amidyl radical is implemented by HRP. Six different methods (Figure 2c), which have been developed for visible-light mediated reactions, could generate

• insight in the development of novel methods for amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer. Although, amidyl radicals employed in many reactions as HAT reagents via heating conditions have been summarized in several studies [52][53][54][55][56][57][58]. To advance

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

• ], medicine [3], sensing [4] and energy storage [5]. Typically, bulk graphene is obtained using a top-down approach, where graphite is exfoliated using chemical or mechanical methods [6][7]. However, this method does not provide precise control over the structure of graphene and graphenoid materials, which is

• ]indene (6) as black plates in a 32% yield. The azulene-containing isomers of pyrene exhibit azulene-like absorption tailing up to around 650 nm. Interestingly, despite their initial synthesis in the 1950s, no further attempts have been made to synthesize compounds 2 and 6 using more modern methods

• = 1010 nm, which is a strong indicator of its dominant non-alternant character. Traditional methods for synthesizing azulene-embedded PAHs often require harsh conditions, making them challenging to apply to larger π-scaffolds. Furthermore, these methods frequently suffer from low yields and are not

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

• rapid construction of complex molecular architectures. This review aims to summarize the diverse strategies for inducing intramolecular transformations of N-arylacrylamides using various carbon radical reagents, including methods initiated by photonic, thermal, or electrochemical processes, which have

• methods utilizing electron donor–acceptor (EDA) complexes and peroxide initiators have recently gained attention due to their operational simplicity and environmental friendliness. In 2024, Song’s group and co-workers presented a novel metal-free, visible-light-promoted method for synthesizing

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

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

• ], etc.) and strong oxidants (K2S2O8 [46][54], Mn(OAc)3 [56][57], organic peroxides [51][58][59], etc.) are employed in these approaches. Modern photocatalytic [47][50][60][61] and electrochemical [48][62] methods were also recently reported. Although several successful oxyphosphorylation reactions

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

• QM methods. We determine the relevant reaction sites either by a set of SMART patterns or by screening all possible reaction sites using the Merck molecular force field calculated ring strain energy, for details see section “Beyond ortho-directing groups”. This restriction allows us to rapidly

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

• complex structure, remains an attractive target for synthetic organic chemists worldwide. Several comprehensive reviews on borrelidin have been published, with a strong focus on its synthesis. The first notable comparison of total synthesis methods was conducted by Ōmura in 2005 [48], highlighting four

• borrelidin [38]. They highlighted a significant limitation in existing methods for constructing the deoxypropionate unit of borrelidin, which features four 1,3-alternating methyl groups with a syn,syn,anti-configuration. These methods typically required at least three synthetic steps to iteratively form each

• the various synthetic strategies employed in the construction of borrelidin fragments. By focusing on key intermediates and synthetic methods explored in recent literature, we have highlighted the feasibility and versatility of different approaches. These methods offer valuable insights into 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

• cell line HEK293. Supporting Information Supporting Information File 44: Complete experimental methods, crystallographic data for 2, 7, 10 and 15, characterisation data and 1D/2D NMR spectra (1H, 13C, COSY, HSQC and HMBC) for 2–15. Acknowledgements The authors wish to thank and acknowledge the

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

• several methods, with highlight to gravity concentration (based on the higher density of gold), cyanidation, and mercury amalgam [15]. The gravity method is a simple and, from the viewpoint of the environment, relatively harmless process that works well as a stand-alone for high-density gold particles and

• is the development of microbial leaching methods [18]. These resort to either cyanogenic microorganisms, such as Chromobacterium violaceum, Pseudomonas fluorescens, and Pseudomonas plecoglossicida, which incorporate gold into their unicellular bodies when grown in the presence of gold-containing e

• -waste [21], or to acidophilic microbes such as chemolithotrophic bacteria and archaea, which can accelerate the oxidative dissolution of gold sulfides in a biotechnological extraction process suited for sulfidic ores [22]. Microbial leaching methods are not, however, implemented at the industrial scale

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

• derivatives were obtained under asymmetric catalysis with a Ni(II)–bisoxazoline complex [15] and a Nd(OTf)3/N,N'-dioxide/LiNTf2 delay catalytic system [16], respectively (Scheme 1b and c). However, further exploration for convenient asymmetric catalytic synthetic methods is still in demand because the former

• ) was attempted as well, delivering the expected product 3ga in 70% yield and 38% ee, illustrating that the 3-aryl group of aziridines 1 also has an important effect on the enantioselectivity in the (2 + 3) annulation. Compared with previously reported methods, our current method is more convenient and

• afford the pure product 3. The enantiomeric excess was determined using chiral HPLC analysis with a mixture of iPrOH and hexane as eluent. Oxazolidine-containing bioactive compounds. Asymmetric catalytic synthetic methods of oxazolidine derivatives. Scope of aziridines and aldehydes. Proposed reaction

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

• construction, alkyne hydrogenation, ylide and carbene reaction, metathesis, E/Z isomerization, and other methods, including Cα and Cβ functionalizations. Preparing various functional group-tethered aromatic groups can be achieved by directly installing an aromatic group via cross-coupling reactions and other

• /N-acylation reactions, metal catalysts, particularly precious transition metals, are considered less sustainable due to their limited availability. Therefore, metal-free catalysis methods have emerged as an alternative to respond to the green chemistry agenda. For instance, Huy and Mbouhom (2019

• -cinnamic acid esters 383–385 and amides 386 and 387 via zwitterionic allene species 389 (Scheme 83B) [142]. 3.1.2 Ylide reactions: The construction of double bond ylide reactions (e.g. Wittig and Horner–Wadsworth–Emmons reactions) is one of the most reliable and stereoselective methods. Several

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

• ] and photopolymerization [10][11][12]. For these reasons, several strategies starting from different carbon-based materials have been proposed and optimized to prepare CDs. In general, such methods are classified in two categories, namely “top-down” and “bottom-up” [1][2][3][4][13]. In the top-down

• , organosilanes). The latter strategy is the most prevalent one, due to the simplicity of the procedures, environmental friendliness, and equipment required, as well as the ability to use a large variety of precursors. In the bottom-up synthesis methods, conversion of the carbon precursors is obtained by having

• different chemical treatments (hydrothermal and pyrolytic methods). The effect of nitrogen doping on the performance of the examined CDs has been also investigated. Results and Discussion Synthesis, photophysical and electrochemical properties of CDs. As hinted above, CDs have been prepared from different

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

• palladium catalysts with amines as nucleophiles have been reported [14][15][16][17][18][19][20][21][22][23][24][25], there have been only a few reports on the N-substitution of isatin using asymmetric methods. Recently, Wolf’s group reported a transition-metal-catalyzed (Pd-catalyzed) asymmetric allylic

• allylic amination of acetate 12 with isatin (11a).a Supporting Information Data of thermal racemization of 7, DFT calculations for investigating racemization mechanism of 7, general methods and materials, experimental procedures and characterization data, 1H, 13C and 31P NMR spectra for 9 and 10, 1H, 13C

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

• , these methods offer promising strategies for the total synthesis of complex natural products. Review Aza-Prins cyclization – total synthesis of (−)-dihydrolycopodine and (−)-lycopodine Cyclizations of enamides can proceed via several distinct pathways. If protonation of the enamide occurs first, the

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

• delves into the photoluminescent properties and spin ground states of trityl-based mono-, di-, and multiradicals, examining the strategies employed to enhance their performance. Additionally, we review predictive methods for determining the luminescence and spin states of radicals, highlighting critical

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

• synthetic methods to access diazepines fused with other nitrogen-containing heterocycles towards their broader exploration in high-throughput screening for identifying new drug candidates. Traditional synthetic methods for producing medium-ring nitrogen-containing heterocycles often involve complex

Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals

• Sally Bloodworth,
• Cerys Willoughby and
• Simon J. Coles

Beilstein J. Org. Chem. 2025, 21, 864–876, doi:10.3762/bjoc.21.70

• organic chemists, a myriad of different file formats across multiple spectroscopies are compounded by a lack of methods to collect, clean and label data in a way that makes it reusable and interoperable, especially for use by machines. Despite the barriers there are good reasons for organic chemists to

• findings suggest about the impact of author guidelines upon researcher practice. Methods 12 Specialist journals with a broad scope around the central discipline of synthesis, catalysis, and methods development in organic chemistry were selected for analysis (Table 1). Criteria for journal selection are

• article cited or linked?’ assesses if it is possible to trace data back to the original publication where the methods used to generate those data are described. 76% of primary data had a citation, however, publisher-led copying of SI files to Figshare positively distorts this proportion, as the repository

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

• ], but can also be readily converted into other functional compounds under specific conditions [4][5]. Due to their significant biological relevance and potential applications, numerous synthetic methods have been recently developed to synthesize these useful intermediates [6][7][8][9]. Among these

• methods, the cascade reaction between ortho-halogen (e.g., chlorine, bromine or iodine) substituted benzoic acids and amidines has become a prominent route to synthesize the corresponding quinazolinones [10][11][12][13][14][15][16][17][18]. In 2009, Fu and co-workers found that copper(I) could effectively

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• LED in CH3CN.a Overview over thermal half-lifes for NAc-PAPs in CH3CN at 30 °C. Eyring analysis of NAc-PAP-CN and NAc-PAP-OMe determined in toluene (for details see Supporting Information File 1, section 3.7). Supporting Information Supporting Information File 46: Materials and methods, analytical

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

• , while density functional theory (DFT) calculations provided insights into their electronic properties, including reactivity and stability. This comprehensive approach, integrating synthesis, biological evaluation, and computational methods, highlights the potential of 4-(1-methylamino)ethylidene-1,5

• development targeting iNOS-related pathologies. Future research should prioritize extensive in vivo studies and clinical evaluations to further explore their therapeutic potential and safety profiles. Experimental Experimental methods All chemicals were purchased from Merck, Sigma-Aldrich and Acros without

• determine the melting points of all products. All NMR spectra were recorded on a Bruker Avance II+ 600 MHz instrument and chemical shifts (δ) are reported in ppm (parts per million) relative to tetramethylsilane (TMS) or internal deuterated solvent signals. Computational methods Prediction of drug-likeness

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• Babak Kaboudin Milad Behroozi Sepideh Sadighi Fatemeh Asgharzadeh Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran 10.3762/bjoc.21.61 Abstract In this review, we describe recent advances in electrochemical green methods for the

• . Electricity can perform the oxidation and reduction process by exchanging electrons on the electrode surface in a region called the double layer (DL) [12]. Unlike traditional methods that require high temperature, pressure, and external oxidants, electrochemistry is an efficient and energy-saving approach

• that controls reaction selectivity by adjusting voltage or current [13]. Simple synthetic systems in electrochemical methods are limited to electrodes, cells, electrolytes, and power supplies. Today, in addition to the above, light, metallic, and organic catalysts are also used to increase the

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• hydrocyanation of hydrazones, catalyzed by a calcium–BINOL phosphate complex, has been studied for the first time both experimentally and computationally with DFT methods. A full catalytic cycle for the enantioselective synthesis of α-hydrazinonitriles is proposed based on insights gained from DFT calculations

• configuration opposite to the results with in situ-formed Ca complex 6, for which BINOL phosphate was newly synthesized, instead of purchased, and with which we achieved much higher ee values (87–89% ee (R), Table 2, entries 1–3). These distinctly different outcomes, when methods to generate Ca complex 6, or

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• target binding will incur little entropic cost) and high selectivity (since off-target interactions will be minimised) [1]. There are several methods by which the conformations of small molecules can be controlled, but in this review we will focus upon one particular method, which is the installation of

• recognition processes. Therefore, methods for controlling the conformations of sugars are likely to have diverse and valuable applications in biotechnology and medicine. The structure of a sugar molecule offers several potential locations where fluorine can be introduced. Typical patterns include the

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• eponymous Tsuji–Trost reaction, they faced a significant limitation: poor regioselectivity with non-symmetrical allylic substrates 2. This constraint led to the predominant development of Pd-catalyzed methods using symmetric 1,3-disubstituted allylic substrates 1 that contain a leaving group in the allylic

• Following the initial demonstration by Buchwald that styrenes are viable substrates for the CuH-catalyzed hydroallylation, the development of methods applicable to vinylboronic esters presented unique opportunities for the synthesis of versatile chiral organoboron compounds [52]. A breakthrough in this

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• and the development of efficient synthetic methods to access these medicinally relevant structural motifs. Herein, we report an electrochemical synthesis of 2-aminoproline and 2-aminopipecolic acid derivatives 6 (Figure 1). Recently, we disclosed an electrochemical approach to tetrahydrofuran and

• NMR methods, and all attempts to obtain crystals suitable for X-ray crystallographic analysis were unsuccessful. N-Protected 2-aminoproline derivatives 6 are relatively stable under basic conditions as evidenced by successful hydrolysis of the ester moiety in 6a,d,e using aqueous LiOH to provide acids