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

• the C–C double bond, that most commonly require some form of catalysis. Thus, developing catalyst-free processes presents significant challenges, although there are few successful examples in the literature [44]. Similar to the dihydrobenzimidazoles above, the investigations here also started with an

• form of catalysis from simple acids to metal catalysts [46]. Similar to the previous examples, the first step was the optimization of the conditions using the esterification of benzyl alcohol (12a) with acetic anhydride (8) and acetic acid (13), respectively. The optimization data are summarized in

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

• catalysis and proceed through a double addition mechanism. In 2011, Mikami et al. developed a catalytic asymmetric oxetane synthesis from silyl enol ethers 89 and trifluoropyruvate 90 using a chiral Cu(II) complex (Scheme 24) [67]. Besides excellent yields, they also observed very high cis/trans ratios and

• amidine base catalysis (Scheme 25b) [69]. Although this methodology employs equimolar catalyst loadings, the products 100 are obtained with complete diastereoselectivity and mostly in moderate to good yields. As for the mechanism, it is assumed to be analogous to the NHC-variant. Four years later, Somappa

• unprecedented Fe–Ni dual catalysis (Scheme 36) [86], which constitutes a more versatile alternative to Minisci or Friedel–Crafts alkylations. The reaction couples mono-, di- and trisubstituted olefins with (hetero)aryl halides, and it was used to prepare a relatively large library of 3-alkyl-3-(hetero

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

• across diverse bond activation challenges, particularly in C(sp³)–H, C(sp²)–H, S–H, Ge–H, and B–H bond transformations. The proposed system architecture emphasizes synergistic reagent cooperation rather than isolated component performance, representing a paradigm shift in photoredox catalysis design

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

• quinolinone products. Beyond electrochemical protocols, photochemical activation – particularly visible-light photoredox catalysis – has become a powerful and sustainable strategy for generating carbon radicals under mild conditions. In 2023, Fan’s group discovered a radical cyclization of N-arylacrylamides

• with α-aminoalkyl radicals generated from tertiary arylamines using photoredox catalysis (Scheme 13) [9]. In this system, Ir[dF(CF3)ppy]2(dtbbpy)PF6 was used as a photosensitizer to trigger the α-C–H activation of N,N-dimethylaniline, generating an alkyl radical under 30 W blue LED (454 nm) irradiation

• versatility of photoexcited palladium catalysis in radical transformations. Furthermore, the method utilizes the readily available Pd(PPh3)4 complex as the sole catalyst, making it operationally simple and cost-effective. In 2021, Wang’s group introduced a novel transition-metal-free, aldehyde-free strategy

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

• bonds in organic chemicals. Therefore, their selective functionalization is essential for advancing the synthesis of complex molecules like pharmaceuticals, polymers, or agrochemicals [1][2][3]. Advancements in organometallic catalysis have facilitated significant progress in this area through C–H

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

• step is energetically favorable. Other than furfural, thiophene-2-carbaldehyde (2s) was used for the GBB and N-acylation reactions to make 6t (Scheme 4). The IMDA reaction of 6t was carried out under the catalysis of AlCl3 in dichlorobenzene at 180 °C for up to 24 h, but no compounds 7t and 8t could be

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

• the significant role of asymmetric catalysis in their strategy, utilizing a copper-catalyzed asymmetric 1,4-addition and a ruthenium-catalyzed asymmetric ketone hydrogenation. Fragment 61 was synthesized in 15% overall yield across 19 steps, while fragment 62b was achieved in 32% yield over 11 steps

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

• of racemic and optically active functionalized cis-2,5-diaryloxazolidine derivatives [13][14][15][16]. Racemic cis-2,5-diaryloxazolidine derivatives were prepared under the catalysis of zinc triflate or nickel diperchlorate (Scheme 1a) [13][14]. Later, highly enantiomeric cis-2,5-diaryloxazolidine

• 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

• -dicarboxylates from aldehydes and dialkyl 2-aryl-1-sulfonylaziridine-2,2-dicarboxylates under the catalysis of the readily available salen–Sc(OTf)3 complex (Scheme 1d). The salen ligand can be prepared in one step from enantiopure cyclohexane-1,2-diamines and substituted salicylaldehydes. Results and Discussion

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

• release (82). Numerous cinnamic acid derivatives with electron-withdrawing and -donating groups were converted to the corresponding amides 76–81 in moderate to excellent yields (Scheme 24B) [60]. 2.1.2 Transition-metal catalysis: Several transition metals have been exploited to catalyze O/N-acylations of

• cinnamic acid (7) to give amide 12 in excellent yield via Ti(IV)–O=C complex 102 (Scheme 31C) [69]. 2.1.3 Photocatalysis: Photoredox catalysis has gained much attention as a sustainable alternative approach to performing O/N-acylation by utilizing light as a renewable source. For example, Li and co-workers

• compounds and N-acylbenzotriazole 97 (Scheme 36) [71]. In this work, the photoactive [FeCl4]− formed in situ triggered silyl radical 119 generation, leading to N-silylamine 120 as the active amine nucleophile. 2.1.4 Metal-free catalysis: Despite the wide applications of metal-based catalysts in developing O

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

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

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

• . Keywords: alkynes; catalysis; cyclizations; domino reactions; heterocycles; Introduction Pyrimidines and purines are one of the most important heterocyclic compounds with prevalent biological functions. Both are found in nucleosides and their corresponding polymeric DNA and RNA, and hence are vital for

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

• column chromatography was required during this process, the synthetic route is highly practical. The enantioselective annulation of tertiary enamide 28 with enoldiazoacetate 29 was then explored under the catalysis of a chiral dirhodium catalyst. While Doyle and co-workers had previously reported an

• alkaloids, though it features a truncated cyclopentane rather than the characteristic cyclohexane or cyclohexene. In their optimization studies, the authors found the sequential catalysis of a chiral binol–Ti complex and BF3·Et2O to be the most efficient, providing products 39 in high yields with excellent

• -silyl substituted cyclopentanone 41, and acyl chloride 42 produced enamide 43. The polycyclization then took place under the catalysis of Cu(OTf)2/L3 and In(OTf)3, delivering tricyclic product 44 in high yield with excellent enantioselectivity. Despite formation of multiple diastereomers due to 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

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

• demonstrate that these simple D–A structures exhibit promising photocatalytic properties, comparable to those of more complex D–A–D systems. Keywords: donor–acceptor system; photocatalyst design; photoredox catalysis; organic photocatalyst; Introduction In recent years, photocatalysis has emerged as a

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; 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

• ) [46]. In 2019, Li, Yang, Van der Eycken and co-workers reported a modification of this strategy relying on thermal activation instead of cationic gold catalysis [47]. The approach worked particularly well with substrates featuring terminal alkynes. Inspired by these developments and taking into

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

• increasingly attracted attention [5][7][8][9][10][11][12][13][14], for example, in 2024, Rana [15] and co-workers reported advances in solvent-controlled stereodivergent catalysis. Surprisingly, to our knowledge, there is currently no comprehensive review of studies on controllable/divergent synthesis. This

• control The precise regulation of product selectivity represents a fundamental challenge in transition-metal-catalyzed organic transformations, with significant implications for complex molecule synthesis. In this context, ligand-modulated divergent catalysis has emerged as a paradigm-shifting strategy

• L9, and reagents, delivering enantioenriched 2-/3-alkyl-substituted pyrrolidines with excellent regio- and enantioselectivity (up to 97% enantiomeric excess). Radical-clock experiments and deuterium-labeled silane studies revealed that cobalt catalysis proceeded via irreversible Co–H migratory

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

• are shown to undergo a rare dimerization process when reacted with bis(pinacolato)diboron under copper catalysis. The reaction provides densely functionalized products with excellent levels of chemo-, regio-, and diastereoselectivity. This high degree of functionalization makes these products

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

• 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

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

• , Germany 10.3762/bjoc.21.69 Abstract The photoactivation of organic molecules via energy transfer (EnT) catalysis is often limited to conjugated systems that have low-energy triplet excited states, with simple alkenes remaining an intractable challenge. The ability to address this limitation, using high

• , and control reactions support sensitization, enabling an intramolecular [2 + 2] cycloaddition to be realized accessing 3D bicyclic fragments containing a boron handle. Keywords: boron; catalysis; [2 + 2] cycloaddition; energy transfer; photochemistry; Introduction The strategic use of a photon to

• prohibitively high in energy for selective reactivity [5]. The inception of energy transfer catalysis (EnT) has expedited discoveries concerning the photoactivation of organic molecules [15][16][17], enabling direct access to the triplet excited state through the use of a photocatalyst (Figure 1A, top

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• , is prevalent across various disciplines including biology, chemistry, materials science, and ion batteries [1][2][3]. Fundamental understanding of ion-pairing can help to regulate their roles and relevant applications in chemical catalysis, battery performance, and ion binding, transport and

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

• response, respiratory, vasodilation, apoptosis, tumor growth, and cardiovascular system [1][2]. Nitric oxide (NO) is released as product of the NADPH and oxygen-dependent oxidation of ʟ-arginine to ʟ-citrulline under the catalysis of the enzyme nitric oxide synthase (NOS) [3]. There are three distinct

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• heat, catalysis, or an electrochemical input [4][5][6], the stored energy can be released converting the molecule back in the parent form (Figure 1). Typical MOST systems are azobenzenes (E/Z-isomerization) [7][8][9][10], the isomerization of dihydroazulenes/vinylheptafulvenes [11][12][13], conversion

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

• catalysis; hydrocyanation; regioselectivity; tosyl cyanide; Introduction Acyclic nitriles that incorporate α-all-carbon quaternary centers are highly valuable structural motifs typically found in natural products, biologically active compounds, and synthetic pharmaceuticals [1][2][3][4][5]. These compounds

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

• phosphonates and phosphine oxides using a nickel catalyst. The use of nickel complex is an important and primary factor in the C–P coupling process. Notably, the inexpensive and environmentally readily available nickel catalysis was more effective for phosphorylation than other 3D metals. Moreover, it

New advances in asymmetric organocatalysis II

• Radovan Šebesta

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

• commonly defined as a form of catalysis where a small organic molecule, an organocatalyst, accelerates a chemical reaction. Unlike previously regarded traditional catalysts involving metals or enzymes, organocatalysts are composed of nonmetal elements, such as carbon, hydrogen, nitrogen, oxygen, phosphorus

• organocatalysis. Even toward the end of the 20th century, there have been a few pioneering studies that should be counted as examples of asymmetric organocatalysis. The works of Jacobsen, Miller, Shi, and Denmark et al. marked the early sparks of interest in this type of chemistry based on catalysis by peptides

• already been described by Seebach et al. in 1982 [15]. From this perspective, organocatalysis is more than 100 years old, building on a long thread of illustrious past discoveries. Asymmetric organocatalysis is now considered one of the three main pillars of asymmetric catalysis, along with metal