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

• , to the best of our knowledge, this study represents one of the few examples of a heterogeneous catalysed copper-mediated C–H amination of benzoxazole. The pursuit for greener methodologies in organic synthesis and transitioning from traditional homogeneous catalysis to the use of heterogeneous

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• Bukireva str., Perm 614990, Russia Department of Organic & Biomolecular Chemistry, Ural Federal University, 19 Mira str., Yekaterinburg 620002, Russia Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, 22/20 S. Kovalevskoy str., Yekaterinburg 620108, Russia Sustainable

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

• largely gone unnoticed as an activation method for organic synthesis. A large number of applications have been reported in solid state, homogeneous and heterogeneous systems to prepare inorganic compounds and materials [7][8][9]. In contrast, high pressure organic chemistry, or HHP-initiated organic

• synthesis is still in its infancy. Despite the recent advances [10][11], the HHP applications in this field are still being developed. The first HHP-assisted organic syntheses were reported in the 1970s [12][13]. Although the mechanism of how pressure enables reactions is not fully elucidated, there is a

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

• demonstrated a decent methodology of organic synthesis. These elegant strategies presented powerful C–H bond transformation toolkits (Figure 1b) [6][7][8]. One of the exceptions to the perfection is the pre-functionalization of substrates. Current catalytic methodologies predominantly rely on substrate

• and the relatively green chemistry of generating amidyl radicals. Amidyl radicals offer several advantages that enhance their applicability in organic synthesis: 1) The BDE of amidyl N–H bond is more than 105 kcal/mol, relative to the bond (C–H, Si–H, B–H, and Ge–H) which BDE is lower than 100 kcal

• with a systematic understanding and strategic toolkit, thereby propelling the development of direct functionalization of C–H, B–H, Si–H, and Ge–H techniques in modern organic synthesis. Most of the photocatalysts used in this review are listed in Figure 3. Review Amidyl radical from N–H bond cleavage N

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

• crucial for fine-tuning their properties. An alternative is the bottom-up approach where various nanographenes are synthesized form smaller building blocks via classical organic synthesis. This strategy enables precise control over the structure and topology, leading to the development of a vast array of

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

• been extensively investigated by researchers. Keywords: carbon radical reagents; intramolecular transformations; N-arylacrylamides; oxidative difunctionalization; radical reactions; Introduction Alkenes, as abundant and versatile feedstocks, have been widely employed in organic synthesis

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

• [1][2][3][4][5] due to the numerous applications of phosphorus-containing compounds in pharmaceuticals, biology, agrochemistry, organic synthesis, and materials science [6][7][8][9][10][11][12][13]. Among various organophosphorus compounds, β-ketophosphonates have received particular attention for

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

• Julius Seumer Nicolai Ree Jan H. Jensen Department of Chemistry, University of Copenhagen, Copenhagen, Denmark 10.3762/bjoc.21.94 Abstract The mild and selective functionalization of carbon–hydrogen (C–H) bonds remains a pivotal challenge in organic synthesis, crucial for developing complex

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

• photooxidant or photoreductant in the presence of a suitable electron donor or acceptor [18], and these properties have been exploited in procedures for the formation of both C–C and C–heteroatom bonds [18][19]. Our research groups recently focused on the application of CDs in light-mediated organic synthesis

• have been considered as a promising source of aryl radicals and employed in organic synthesis [20][21][22][23][26][27][28][29][30][31][32]. This investigation aims to compare the performance of CDs prepared from several carbon precursors including citric acid, glucose, and organic waste materials via

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

• followed by deprotection completed the total synthesis, giving rise to (−)-cephalocyclidin A in 10 steps from known compounds. Conclusion In summary, the perception of enamides as stable chemical entities with limited utilities in organic synthesis has evolved, and these compounds are now widely used 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

• generate cyclosiloxanes. An alternative pathway involving cleavage of another Si–O bond during the conversion from 55 to 56 and subsequently to 57 cannot be excluded. Temperature control Temperature, as a readily adjustable physical parameter in organic synthesis, offers a simple and versatile approach to

• , while the thermodynamic and kinetic properties of different reductive elimination intermediates jointly determine the switchable site selectivity. Acid–base control The strategic modulation of acid–base interactions has emerged as a powerful paradigm in organic synthesis, enabling precise control over

• radical anion, followed by cyclization and dehydration to yield bicyclic product 76. Substrate control Substrate control has emerged as a powerful strategy in organic synthesis, enabling precise manipulation of reaction pathways and stereochemical outcomes through the intrinsic structural and electronic

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

• considering recent advances enabling subsequent intramolecular H-atom abstraction [51] and efficient rearrangements [73][74]. A) Energy transfer catalysis of alkenes in organic synthesis. B) Energy transfer catalysis of conjugated borylated alkenes. C) Energy transfer catalysis of simple alkenylboronic esters

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

• and amino groups in III yields the target quinazolinone 3. To demonstrate the practicality of this reaction in organic synthesis, the reaction was scaled up to the gram level. For instance, the desired product 3a was obtained in 91% yield (1.45 g) when the reaction was conducted on a 10.0 mmol scale

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

• with diverse functional groups [12][13][14]. Consequently, the development of selective and predictable strategies for the introduction of cyano groups into quaternary carbon frameworks has become necessary in organic synthesis. The transition-metal-catalyzed hydrocyanation of carbon–carbon double

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

• on the aromatic ring did not react in this system due to the incompatibility of the intermediate radicals. Electrochemical N–P bond formation Due to the importance of phosphoramidates in medicine and organic synthesis, Zhong et al. [64] reported an electrochemical P–N coupling of amines with dialkyl

• )(OR)2. The final product was formed by a simple nucleophilic substitution of the phosphorus center (Scheme 20). The N–P bond formation is a critical process in organic synthesis due to the preparation of various materials with different biological and medicinal activities. In 2021 Wang et al. [65

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

• generation of chiral secondary alkylcopper species has been a significant challenge in organic synthesis, primarily due to their inherent instability and tendency to racemization [38]. For generating the key chiral organocopper intermediates, two distinct approaches have been developed: one utilizing chiral

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

• Olesja Koleda Janis Sadauskis Darja Antonenko Edvards Janis Treijs Raivis Davis Steberis Edgars Suna Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia Faculty of Medicine and Life Sciences, Department of Chemistry, University of Latvia, Jelgavas 1, Riga LV-1004, Latvia

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• of its unique interaction in organic synthesis. Chiral halonium salts have been found to have strong halogen-bonding-donor abilities and work as powerful asymmetric catalysts. Recently, we have developed binaphthyl-based chiral halonium salts and applied them in several enantioselective reactions

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

• Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy 10.3762/bjoc.21.33 Abstract Photomechanochemistry, i.e., the merger of light energy and mechanical forces, is emerging as a new trend in organic synthesis, enabling unique reactivities of fleeting excited states under solvent

• photons and forces, streamlining the combination of mechanochemical and photochemical processes and paving the way for more efficient, sustainable, and selective transformations in organic synthesis. An unexplored opportunity is offered by resonant acoustic mixing (RAM) [82], a technology that leverages

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• Andrejs Savkins Igors Sokolovs Latvian Institute of Organic Synthesis, Aizkraukles 21, 1006 Riga, Latvia Faculty of Medicine and Life Sciences, University of Latvia, Jelgavas 1, 1004 Riga, Latvia 10.3762/bjoc.21.32 Abstract The remarkable nucleofugality of bromoarenes in diarylbromonium species

• Belyakov from the Latvian Institute of Organic Synthesis (LIOS) for X-ray crystallographic analysis. We also thank Prof. Edgars Suna (LIOS) for helpful discussions and assistance in preparing the manuscript. Funding This work was financially supported by Latvian Science Council grant LZP-2021/1-0595.

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• ability to operate under low-energy light conditions, opens up new avenues for main-group redox catalysis in organic synthesis. By leveraging light excitation to enhance the reducing power of the bismuth complex, the study showcases the potential of main-group photoredox systems to complement traditional

• findings suggest that cyanins, specifically tailored to absorb in the NIR region, exhibit promising redox properties for applications in organic synthesis. A recent work by Goddard et al. has demonstrated that compound 46 is highly effective in various photoredox transformations, such as aza-Henry

• potential applicability [70]. Values are given in Figure 13. The first results obtained in organic synthesis have consisted in the dual Pd/DMQA-catalyzed C(sp2)–H arylation with aryldiazonium such as 56 with lactam derivative 57, which have leaded to similar results as the traditionnal use of Ru(bpy)32

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• have made them to become valuable building blocks in organic synthesis. Nucleophilic additions or spiroannulation of the highly reactive carbonyl group at the C-3 position of isatins have various fascinating applications in organic synthesis, which allowed transformation of isatins into various

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

• groups in organic synthesis [1][2][3][4]. In chemistry and biology, disulfide bonds play crucial roles in protein folding and stabilization [5][6][7][8] and in the rubber industry, they are used to link different polymer chains [9][10]. The disulfide bond backbone is commonly used as a linker for

• antibody–drug coupling (ADCs), in which the active drug released in the target cell by selectively breaking the disulfide bond [11]. Given the wide applicability of disulfides, the development of efficient, green, mild, and cost-effective methods for the organic synthesis of disulfides is of significant

• sulfinate (Scheme 1) [29][30][31][32]. Among the available alternatives, sodium sulfinate is particularly interesting because it is more stable and easier to transport, and it is widely used in organic synthesis [33][34][35][36][37]. When using sodium sulfite as the starting material for the construction of

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

• increasing interest as affordable, versatile, and sustainable catalytic systems. These catalysts are extensively employed in organic synthesis owing to their cost-effectiveness, reduced toxicity, and natural abundance [20][21][22][23][24][25][26][27][28]. The use of copper salts has enabled a variety of

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

• –heteroatom (C–X, where X = N, O, or halogens) bonds in organic synthesis. Copper was one of the first transition metals employed in cross-coupling to form C–C and C–X bonds [1][2]. In 1901, Ullmann reported the first cross-coupling reaction for the formation of biaryl compounds in the presence of

• ’ and Fu’s asymmetric C–N bond cross-coupling reactions by merging photoredox catalysis with copper catalysis [29][30]. Building on the success of photoredox catalysis, electrochemistry has emerged as a complementary and attractive strategy for promoting sustainability of organic synthesis. By offering

• catalysis to organic synthesis, focusing on recent developments in Cu-catalyzed electrochemical reaction categorized into four types: 1) C–H functionalization, 2) olefin addition, 3) decarboxylative functionalization, and 4) coupling reactions (Figure 3). This review aims to provide insight into the