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

• 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

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

• leukaemia, and TAK-285 (H) is a promising HER2/EGFR inhibitor which has been tested in a phase 1 trial on humans as an anticancer agent (Figure 1) [16]. Given the significance of deazapurines as biologically active lead compounds [22], we developed a new methodology for the synthesis of uracil-based

• 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

• groups of those compounds. In contrast, compounds 4a and 4m showed only weak fluorescence with quantum yields of 9 and 4%, respectively. Compound 4j exhibited almost no emission (Φ = 0.1%). [30]. Conclusion In summary, we developed a new methodology for the synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H

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

• showed a better performance in comparison with the D–A–D compound 3 (Table 3, entry 7). Furthermore, we obtained pleasing outcomes when we tried the photocatalyzed reductive pinacol coupling of benzaldehyde (15), as reported by Rueping [38]. In this methodology, the reduction of compound 15 is

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

• pyrazolodiazepines 16w and 16x, respectively. Such an outcome is notable, as related carbocyclizations often switch to an exo mode when shifting from internal to terminal alkynes [61][62][63]. To demonstrate the robustness of our methodology, we tested a telescope procedure in which, after the Ugi step, the product

• of post-Ugi transformations leading to the formation of fused seven-membered heterocycles. A series of target pyrazolodiazepines were generated through the variation of substitution patterns on all components of the Ugi reaction while several limitations of the methodology were also identified. In

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

• reduced electrophilicity of the ester carbonyl. In 2021, Dong and Xie reported the development of an azido Matteson reaction, which achieves carbene insertion into an N–B bond of aminoboranes 84 or 86 (Scheme 22) [53]. In this methodology, by controlling the carbene leaving group (alkyl chlorides/alkyl

• (such as indole substrates), Int-79 is more stable at −78 °C, favoring the formation of the mono-insertion product 86. In 2022, Wu and colleagues reported a novel methodology for constructing α-ketoamides 90 or 92 and amides 91 through copper-catalyzed dicarbonylation and monocarbonylation reactions

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

• ). We have studied this reaction and now report a catalytic methodology for the diastereoselective synthesis of these dimeric structures. The high degree of functionalization present in these molecules, which feature two ester groups, an aliphatic gem-dichloride and a dichloroalkene unit, offers ample

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• by the regio- and stereoselective allylation with p-toluenesulfonyl cyanide. The proposed methodology is efficient for accessing acyclic β,γ-unsaturated nitriles with α-all-carbon quaternary centers and achieves yields up to 99% and excellent regio- and E-selectivity. The reaction proceeds under mild

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• -catalyzed reactions and biocatalysis. In the past 25 years, organocatalysis has grown rapidly into a broad area of research, with industrial applications now being developed [16]. The usefulness of any idea or methodology is ultimately often measured by its applications. The robustness, reliability, as well

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• as trifluorovaline and trifluoroisoleucine were synthesized on a gram‑scale with excellent enantiomeric purities. In this work, we increase the scope of this methodology even further. First, we present the synthesis of two fluorinated, aromatic amino acids: (2,3,5,6)-tetrafluoro-4

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

• Abstract The transition-metal-catalyzed asymmetric allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction. Particularly, the generation and utilization of chiral secondary alkylcopper species have received considerable

• secondary organocopper; copper-mediated reaction; stereoselectivity; Introduction The transition-metal-catalyzed regio- and enantioselective allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction [1][2][3][4]. The

• dialkylzinc reagents as nucleophiles [26]. They subsequently expanded the methodology by successfully employing triorganoaluminum reagents [27]. Recent developments in transition-metal-catalyzed AAA have increasingly turned to organoboron compounds [28][29][30][31]. These reagents offer numerous advantages

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• traps the sulfonium ylide (Scheme 16). In an independent work, Mhaske et al. proposed an alternative methodology to furnish β-amino ketone 20a (Scheme 17), using DMSO as a formaldehyde surrogate but with activation via ammonium persulfate (APS), avoiding the use of transition-metal catalysis [51]. In

• amine with two methyl groups and a benzyl or allyl group, the cleavage of the N–CH2Ph and N–allyl bond takes place more selective (by 85% and 67%, respectively), instead of the cleavage of an N–Me bond. This explains the high selectivity observed for some examples in Scheme 27. Finally, this methodology

• source of formaldehyde but not for ammonia, so the methodology can be used with other amines, too (Scheme 29). Glyoxylate derivatives Due to its low toxicity and reactivity, glyoxylic acid and its glyoxylate derivatives are among the most interesting formaldehyde surrogates in multicomponent reactions

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• . Several homoallylic trifluoromethyl carbinols functionalized with a pyrazole moiety were obtained under mild reaction conditions (27–80% yield). This methodology provides a straightforward access to an unprecedented class of trifluoromethyl carbinol derivatives offering a new synthetic approach to

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• organometallic catalysis [15], enzymatic catalysis [16], aminocatalysis [17][18][19], and hydrogen-bonding catalysis [20][21][22]. The Michael addition reaction is a versatile synthetic methodology that allows the formation of new carbon–carbon and carbon–heteroatom bonds through the coupling of electron-poor

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• light and promote mass transfer. As understanding of the methodology advances, the development of more complex synthetic strategies, including C–H, C–C, and C–heteroatom-bond formation, is expected [79]. Moreover, we anticipate that the difference in photophysical properties between organic molecules in

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• antibacterial [4] and cytotoxic activity [6][7]. Existing approaches to the synthesis of 1,3-tropolone derivatives have a number of drawbacks, namely, limited synthesis methodology and low yields of the target compounds [8][9][10][11][12][13][14][15]. Over the past decade, only a few reports have been published

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• tetrabutylammonium iodide (TBAI)/H2SO4 reduction system using sodium sulfinate as key component, thus eliminating the need for thiols and redox reagents commonly used in traditional methods. Various disulfides and 3-sulfenylchromones were obtained in moderate to excellent yields through this methodology. Mechanistic

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• benzimidazole ring also successfully underwent smooth cyclization, leading to the formation of products 3c and 3d. Furthermore, the methodology was compatible with 5,6-disubstituted N-alkenylbenzimidazoles, including those with -difluoro, -dichloro, -dibromo, and -dimethyl substitutions, resulting in the

• demonstrates the versatility of our methodology and its potential for further exploration in diverse chemical spaces. To gain a deeper understanding of the mechanism behind the observed reaction, we conducted a series of control experiments as outlined in Scheme 3a. Initially, we performed the model reaction

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• synthetic methodology for N-arylamides 13 from dioxazolones 11 and boronic acids 12 using copper salts (Scheme 5) [90]. As illustrated, dioxazolones with both electron-rich and electron-poor substituents, including alkyl substituents, were well-tolerated, providing the desired products 13a–h. However, the

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• Wentao Yu Zhiyao Yang Chengkan Yu Xiaowei Li Lihua Yuan College of Chemistry, Sichuan University, Chengdu 610064, China 10.3762/bjoc.21.10 Abstract Orthogonal self-assembly represents a useful methodology to construct supramolecular polymers with AA- and AB-type monomers, as commonly used for

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• chemistry. Combining electrochemistry with transition-metal catalysis is a promising and rapidly growing methodology for effectively forming challenging C–C and C–heteroatom bonds in complex molecules in a sustainable manner. In this review, we summarize the recent advances in the combination of

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• across various applications. In this study, we present a comprehensive methodology for synthesizing, self-assembling, and transforming polysarcosine-poly(benzyl glutamate) block copolymers, resulting in the formation of bowl-shaped vesicles, disks, and stomatocytes. Under ambient conditions, the shape

• addition water – this process was facilitated by the glass-transition temperature (Tg) of the polymer, marking the transition from a fluid to a glassy state. To replicate this methodology, it is important that the Tg of PSar-PBLG is high enough to freeze the different morphologies by water addition. The Tg

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• tasks and reducing the overall process development lead time [3][4]. A standard workflow and general methodology for organic reaction optimization through ML methods is shown in Figure 1. The workflow comprises (i) careful design of experiments (DOE); (ii) reaction execution with commercial high

• , with dedicated literature offering concepts behind droplet formation [41][42]. An example of a segmented flow droplet system was employed to screen a range of organic solvents to obtain optimal conditions for the monoalkylation of trans-1,2-diaminocyclohexane [43]. The HTE methodology in combination

• . In addition to organic synthesis, the slug flow methodology has found application in polymer synthesis. A flow platform capable of polymerizing 397 unique copolymer compositions was developed by Reis et al. [51] using a droplet flow reactor. The methodology and high-fidelity data enabled them to

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• azafluoranthene product [43]. In the current work, we report a full account of our studies on the application of the fluoranthene synthesis methodology to a wide range of acenaphthylene-fused heteroarenes (Scheme 1e). Moreover, our method enables the modular syntheses of various differentially protected

• ] or catechol [47] boronic esters as the final products. Therefore, it is important that they can be directly utilized with our methodology without further boronic ester interconversions. To this end, we first tested the reaction of thiophene-3-ylboronic acid pinacol ester (17b), and we were pleased to

•  1 demonstrate that a variety of thiopheneboronic acid and esters are competent substrates in our fluoranthene synthesis methodology. Following the successful results with the use of thiophene boronic acid and esters, we next investigated the scope of our methodology to prepare a variety of other

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• the functionalization of BBX reagents. (Benzylamino)benziodoxolones, BBXs 2, were prepared according to our reported procedure, via reaction with previously silylated benzylamines (Scheme 2) [4]. Using this methodology, a total of four benziodoxolones (including the new p-fluorobenzylamine