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

• arrangements. The ability to precisely control multiple contiguous stereogenic centers would significantly expand the synthetic utility of such transformations, particularly in the synthesis of complex molecules such as natural products and pharmaceuticals [60]. Furthermore, future efforts could also focus on

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• , exceptional thermal and chemical stability, and robust synthetic versatility [16][17] – make carborane derivatives essential components in various fields. These include pharmaceuticals [18][19][20][21][22], boron neutron capture therapy (BNCT) [23][24][25][26], organometallic ligands [27], and functional

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• huge interest in the study of ‘Glycomics’ or ‘Carbohydrate Chemistry.’ These truly elevated the recognition of carbohydrates from being mere building blocks to a frontier research topic towards the development of drugs and pharmaceuticals [12][13], diagnostic tools [14], artificial sweeteners [15

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

• pharmaceuticals and agrochemicals nowadays, largely due to the unique ability of fluorinated groups to influence the physicochemical and biochemical properties of molecules [1][2][3]. Among the various fluorinated functionalities, the difluoromethyl (CF2H) group and its aryl-substituted derivative, the benzylic

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

• leads to the formation of the N-acyl amidine product 10. 1.4 N-Arylation of dioxazolones Amides bearing N-substituents are key structural motifs in a wide range of polymers [82], natural products [83], and pharmaceuticals [84][85]. Conventional synthetic routes for N-arylamides typically involve the

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

• functionalization of highly complex and diverse molecules, such as those of pharmaceuticals and natural products, has provided new retrosynthetic disconnections for complex compounds, contributing to improved resource efficiency [41][42][43][44][45][46]. Recently, the merging of C–H activation and electrochemistry

• important for more sustainable reactions. Furthermore, the application of electrochemical copper catalysis to complex molecules, such as for the late-stage functionalization of pharmaceuticals or materials and bioorthogonal functionalization of biomacromolecules, is necessary. Further advances in Cu

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• important in pharmaceuticals and agrochemicals [41][42][43][44][45][46][47], we expect that this method will provide a novel and efficient approach for producing these valuable compounds. Experimental General: 1H NMR, 13C NMR, 19F NMR, and 31P NMR were recorded on a Bruker Avance 500 or a JEOL ECS-400

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

• promises to unlock new avenues in pharmaceuticals and biomedical engineering. The problem here is that PEG-PS is a non-biodegradable material and this poses significant challenges for its use in drug delivery applications, particularly concerning potential accumulation in the body [5]. Recent advancements

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

• methodology was further examined with (1-methyl-1H-pyrazole-5-yl)boronic acid pinacol ester as the pyrazole ring is one of the most frequently occurring aromatic nitrogen heterocycles among the pharmaceuticals approved by the U.S. FDA between 2013 and 2023 according to a recently-reported analysis [53]. With

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

• reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• has become an essential structural motif in medicinal chemistry due to its hydrogen-bond donor capacity, its lipophilic character, and as a bioisostere for alcohol, thiol, or amine groups [16][17][18][19]. Thus, the contribution of fluorinated compounds to pharmaceuticals has been crucial for more

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• Although less common than fluorine in biologically active compounds, chlorine-containing molecules have interest in drug discovery, with over 250 chloro-containing drugs presently available [43]. The introduction of a chlorine atom into biologically active compounds for use in pharmaceuticals and

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• nucleophiles to unsaturated compounds with electron-withdrawing groups, is a cornerstone in constructing carbon–carbon and carbon–heteroatom bonds [1]. It is instrumental in synthesizing natural products [2][3][4][5] and pharmaceuticals [6], underlining its significance in organic chemistry. Recent

• using organolithium reagents (Scheme 1), revealing new avenues in fluorinated unsaturated amide synthesis, which are present in numerous natural products, pharmaceuticals, and polymers [34][35][36][37][38]. The obtained α,β-unsaturated amides may represent promising structural motifs for further

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• heteroaromatic compounds serve as crucial scaffolds in pharmaceuticals. Therefore, the synthesis of N-substituted heteroaromatic derivatives under mild and environmentally friendly conditions is highly valued. The use of electrophilic diaryliodonium salts for nitrogen arylation has been investigated. Working on

• approach providing regioselective access to N2-arylated products along with high yields. The synthetic route could also be applied for the synthesis of N2-arylbenzotriazoles which are promising scaffolds for pharmaceuticals. Subsequently, the impact of the aryl group present in the diaryl iodonium salts on

• reaction that results in the formation of diaryl ethers. Diaryl ethers are important structural motifs in pharmaceuticals and agrochemicals due to their diverse biological activities. Since the 1950s, one of the most used methods for the synthesis of diaryl ethers involves the reaction of phenol with

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• anode and a foamed Ni cathode, at a constant current of 12 mA in DMSO at room temperature under atmospheric conditions. The reaction has been applied to more than 80 examples, including the late-stage functionalization of natural products and pharmaceuticals, as well as the synthesis and radiosynthesis

• bonded to the nitrogen atom of the aniline substrate. The methodology showcases a broad scope for carboxylic acids and demonstrates multiple examples of LSF of pharmaceuticals and natural products. The proposed mechanism begins with the formation of Ru(II) diacetate through ligand exchange between the

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• Jiapeng Guo Weike Su An Su Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• , anticancer, non-steroidal anti-inflammatory, antihypertensive, antipsychotic, anxiolytic and in other pharmaceuticals [3][4][5]. Therefore, considering the diversity of biological properties, development of reliable approaches for the synthesis of new nitrogen heterocyclic systems is a highly urgent goal

• is 1,2,3-triazin-4-one. Such compounds exhibit a wide variety of biological activities including antitumor, anticonvulsant, diuretic, anesthetic and sedative effects [33][34][35][36]. Also, several commercially available pharmaceuticals used as herbicidal, antibacterial, fungicidal and insecticidal

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• [D3]-formamide. The ability to deuterate at benzylic positions is particularly relevant as benzylic C–H bonds are common in biologically relevant chemotypes and moreover appear in approximately 25% of the top selling 200 pharmaceuticals [23]. Benzyl cation stability is a driver of metabolism at these

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• Organofluorine compounds have attracted great attention in various fields, such as organic materials and pharmaceuticals [1][2][3], because fluorinated compounds sometimes show specific properties [4]. So far, several methods have been developed for the synthesis of fluorinated compounds. Using nucleophilic

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• MacMillan were awarded the Nobel Prize in 2021 for the development of asymmetric organocatalysis [6]. To date, industrial companies have used a number of asymmetric organocatalytic processes to synthesise pharmaceuticals and fine chemicals on large scales [7]. Catalyst recycling is key from both an economic

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• Pengcheng Lu Luis Juarez Paul A. Wiget Weihe Zhang Krishnan Raman Pravin L. Kotian Department of Discovery Chemistry, BioCryst Pharmaceuticals Inc., Discovery Center of Excellence, 2100 Riverchase Center Building 200, Suite 200 Birmingham, AL, 35244, USA Department of Computational Chemistry and

• Structural Biology, BioCryst Pharmaceuticals Inc., Discovery Center of Excellence, 2100 Riverchase Center Building 200, Suite 200 Birmingham, AL, 35244, USA 10.3762/bjoc.20.170 Abstract Herein, we report a pair of regioselective N1- and N2-alkylations of a versatile indazole, methyl 5-bromo-1H-indazole-3

• heterocycles with interesting biological and medicinal properties. Indazole, also called benzpyrazole, is a heterocyclic organic compound commonly found as a structural motif in natural products, pharmaceuticals, agrochemicals, and bioactive compounds [1][2][3][4][5][6]. Indazole-containing compounds possess a

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• ); isoquinolinone; solvent-dependence; Introduction Isoquinolinone is an important heterocyclic structure found in many natural products and biologically active compounds, including pharmaceuticals [1]. For instance, lycoricidine, found in the medicinal plant Lycoris radiata, may inhibit the MCPyV LT protein

• . Selected natural products, pharmaceuticals, and biologically active compounds having an isoquinolinone scaffold. Chemoselective and PISA-mediated, solvent-controlled synthesis of different isoquinolinone derivatives 2 and 3. Substrate scope for the synthesis of 4-substituted isoquinolinones 2. Reaction

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• from ligands for catalysts [2], through pharmaceuticals [3], to organic semiconductors [4][5]. Despite their fundamental and applicative importance to many fields, the vast chemical space of PASs has remained largely unexplored. As a result, the relationships between the arrangement and composition of

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• discussion will also encompass the design of biosynthetic intermediates and their analogs to achieve chemo-enzymatic total syntheses. Given our emphasis on natural products, this review does not cover the exquisite synthetic approaches involving biocatalysts for small-molecule pharmaceuticals. To gain a more