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

• advancements in the synthetic transformations of dioxazolones, with particular examples of copper salts. Keywords: amidation; copper salts; dioxazolones; electrophilic nitrogen; N-acyl nitrene; Introduction Dioxazolones, first synthesized and reported by Beck and co-workers [1], have been employed as

• electrophiles in various nucleophilic transformations due to their susceptibility to rapid decomposition into the corresponding isocyanates (Scheme 1a) [2][3]. They have attracted increasing interest as electrophilic amide sources in amidation using transition-metal catalysts such as ruthenium, rhodium, and

• . Review 1 Transformations via the formation of copper nitrenoids 1.1 C(sp3)–H amidation Lactams are recognized as one of the most significant nitrogen-containing heterocycles in drug discovery [69][70]. Among these, six-membered lactams, known as 2-piperidinones, have been extensively studied due to their

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

• Yemin Kim Won Jun Jang Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Korea 10.3762/bjoc.21.9 Abstract In recent decades, organic electrosynthesis has emerged as a practical, sustainable, and efficient approach that facilitates valuable transformations in synthetic

• electrochemistry and copper catalysis for various organic transformations. Keywords: copper; electrochemistry; radical chemistry; single-electron transfer; sustainable catalysis; Introduction Transition-metal-catalyzed cross-coupling has emerged as an effective method for forming carbon–carbon (C–C) and carbon

• achieved by precisely controlling the potential. Additionally, the merging of electrochemistry and transition-metal catalysis offers advantages in controlling substrate activation, intermediate reactivity, and bond formation, as well as facilitating asymmetric transformations. As a result, electrochemical

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• transition-metal catalysts provides synthetic tools even more advantageously. Copper has also become very interesting in this field, mainly in processes aimed at synthesizing heterocyclic compounds. Among the various catalysts, Cu(OTf)2 stands out in heterocyclic synthesis and ring transformations due to its

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

• -catalysis recently led to an array of intriguing transformations. Axially chiral styrenes 26 were assembled via the NHC-catalyzed reaction of propargylic aldehydes 25, sulfinic acids, and phenols [28]. The crucial step of this transformation is the 1,4-addition of the sulfinic anion to the triple bond of

• a CPA to be used as an organocatalyst or to a phosphoramidite to be used as a chiral ligand. Testing these new structures on known stereoselective transformations, the authors achieved high yields and enantioselectivities (up to 98% yield and 97% ee). Wang et al. performed asymmetric (4 + 3

• authors prepared a wide scope of axially chiral products 186 in high yields with excellent enantiomeric purity. The reaction allows lowering of the catalyst loading to 2 mol %. Deprotection of the amino group enabled subsequent transformations, such as a reaction with isocyanate from which a new potential

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

• -polystyrene block copolymers (PEG-PS) stand out for their versatility and adaptability. These copolymers exhibit a remarkable propensity for self-assembly, allowing the formation of vesicles capable of undergoing diverse shape transformations. Notably, they can adopt the distinctive stomatocyte morphology

• suggests that shape transformations triggered by saccharose are more effective at higher temperatures [38]. Conclusion Self-assembled vesicles crafted from polysarcosine-poly(benzyl glutamate) block copolymers exhibit distinct properties compared to conventional systems like PEG-PS or PEG-PDLLA, notably

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

• transformations based on diazonium chemistry, in parallel (Figure 4). A total of 96 reaction conditions were tested, leading to optimized reaction parameters in less than an hour. Chatterjee et al. [55] introduced the concept of radial synthesis to perform multiple single-step chemical reactions or to decouple

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

• transformations. The umpolung reactivity provided by these iodine reagents enables chemical transformations that would typically demand less environmentally friendly conditions. The investigations conducted in this work confirmed the ability of the novel hypervalent iodine(III) reagents 2 to transfer their amine

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• approaches have also gained widespread attention for their unique advantages in these transformations [4]. Radical chemistry often exhibits complementary reactivity to two-electron pathways and can be performed with high selectivity, atom economy, and functional group tolerance [5]. A well-known radical

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

• -raising activation (amine-based catalysis and N-heterocyclic carbenes), and iii) LUMO-lowering and HOMO-raising activation (bifunctional thioureas and squaramides). Due to the ubiquitous nature of non-covalent interactions in organic systems, they can play a decisive role in asymmetric transformations [15

• carbamate group by interaction with the oxygen atom of the phosphoryl group. Although recently Rana and co-workers published a review article covering catalytic asymmetric transformations of azadienes [16], there is still room for this review which only focuses on non-covalent organocatalyzed cyclizations

• reviews [17][18]. Review Hydrogen bond donors: bifunctional thioureas and squaramides The use of bifunctional catalysts is commonplace in organocatalyzed transformations [19][20][21][22][23]. These catalysts are able to activate an electrophile and a nucleophile simultaneously and in IEDADA reactions they

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• cross-couplings. Schoenebeck and co-workers have shown that Ge-based compounds are versatile reagents within chemoselective cross-coupling processes for the formation of a variety of C–C and C–X bonds [55][56][57][58][59][60][61][62][63]. Importantly, these transformations can take place in the presence

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• -2,2-dicarboxylic acids 6. Transformations of 3-(tert-butyl)-5-chloroisoxazole-4-carbonyl chloride (1j). Synthesis of amides 10. aFiltration through celite after reaction with amine (without aqueous workup). bWork up with H2O. Synthesis of esters 11. Synthesis of dicarbonyl azide 12. Synthesis of 5

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• 10.3762/bjoc.20.263 Abstract A novel study on the hypervalent iodine-mediated polyfluoroalkylation of sulfoxonium ylides was developed. Sulfoxonium ylides, known for their versatility and stability, are promising substrates for numerous transformations in synthetic chemistry. This report demonstrates the

• versatile intermediates in organic synthesis due to their unique reactivity and ability to participate in a wide range of chemical transformations. In this scenario, sulfoxonium ylides are excellent substrates for bifunctionalization reactions, due to the ambiphilic character in their ylidic carbon [16

• ]. This synthetic potential has been demonstrated in a range of insertions into polar bonds [17][18][19][20], C−H activation transformations [21][22][23], and geminal difunctionalizations [24][25]. Within the literature, a broad array of classical methods describes the synthesis of sulfoxonium ylides [26

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• years, the Ugi reaction has emerged as a highly considered reaction due to its mild conditions, broad applications, and product diversity. It enables the selective assembly of precursors, facilitating various post-reaction transformations such as deprotection cyclization, 1,3-dipolar cycloaddition, and

• -Ugi transformations, it is possible to obtain diverse heterocyclic compounds with tetrazole moieties [65]. In this context, Medda et al. [66] developed a three-step process to access biologically active imidazotetrazolodiazepinones. The first one is the AU-4CRs among ethyl glyoxalate, amines

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• a single oligomer across a panoply of different transformations typically range from <1% to ≈30% when n > 1 is desired [35]. To the best of our knowledge, the assembly of functionalized [n]staffanes from 1 in high yield/selectivity and in one step via controlled radical oligomerization remains a

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

• pyrrolidine intermediates A can undergo further transformations (Scheme 10), depending on their structure and the iodane reagent being used. For example, higher yields of 3-fluoropiperidine products 6 were observed when using cyclic iodane reagents 21 and 22 (Scheme 10), which was suggested to be because a

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• recognition, and supramolecular assemblies [9][10][11][12][13]. There are numerous examples of using metalloporphyrins as artificial photosynthesis models, enzyme mimics, and catalysts for various organic transformations, where a metal center acts as an active site [14][15][16][17]. However, metal-free (or

• macrocycles, both synthetic and found in nature, and their ability to act as organocatalysts, metal-free porphyrin macrocycles have a potential to be excellent candidates for green, cost-effective catalysts of various organic transformations including asymmetric synthesis. 2 Metal-free tetrapyrrolic

• light irradiation. There are a few reports on red light-mediated transformations using other pyrrolic macrocycles, such as thiaporphyrin [94], phthalocyanine [95], and subphthalocyanine [96]. Porphyrin macrocycles can also absorb red light (Q bands at 518, 553, 592, and 648 nm with extinction

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• trifluoroethanol to Et3N for the subsequent catalysis). Thus, this protocol enabled a straightforward and rapid synthesis of highly 2-substituted indoles under mild reaction conditions, highlighting the versatility of propargylamine as a bifunctional reagent in post-Ugi-azide transformations. Our group pioneered

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• the two transformations. Studies directed toward a better understanding of possible transition-state structures and the design of new catalysts to improve the results are currently underway in our laboratories. A potential energy surface (PES) for the proposed mechanism for (a) isomerization of

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• of allylic peroxidation 2, 4 and 5 were observed (Scheme 4) [24]. Similar transformations were reported later using CuCl as the catalyst [39]. Later, Gade with coauthors demonstrated the allylic peroxidation of cyclohexane with TBHP using the alkylperoxocobalt(III) complexes [Co(BPI)(OAc)(OO-t-Bu

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

• Poznań, Poland 10.3762/bjoc.20.247 Abstract The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation

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

• various useful transformations under mild, eco-friendly reaction conditions [4][5][6][7][8][9][10][11]. Various review articles [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and books [27][28] have appeared on the chemistry of hypervalent iodine compounds. In the past two decades

• capability to function as radical initiators. The use of diaryliodonium salts as efficient electrophilic arylating reagents in a wide range of organic transformations is due to their unique features such as solid-state nature, excellent stability, and the presence of a robust leaving group [39][40][41][42

• reductive elimination to produce the desired sulfilimine 99 (Scheme 40) [92]. Synthesizing S-aryl xanthates through transition-metal-catalyzed or SNAr reactions presents challenges due to potential additional transformations occurring under the reaction conditions. However, employing diaryliodonium salts

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• . Various reagents and chemical transformations have been elaborated in this context over the years [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Despite these recent advances, the design of highly functionalized

• various transformations [54][55][56][57][58][59][60][61][62][63][64]. In consequence, a large number of transition-metal-catalyzed or radical-mediated processes for C–H functionalization of aldehyde hydrazones has flourished over the years. An ideal scenario for a direct and sustainable synthetic route

• towards trifluoromethylthiolated hydrazones will be the direct C–H functionalization of the corresponding aldehyde hydrazone, an uncharted transformation to date. Forging a C–S bond by the direct C–H-bond functionalization of hydrazones is still underdeveloped. Except for transformations leading to the

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• and 1n were studied. Both gave the expected products in yields of 50% (for 3m) and 44% (for 3n). Besides these successful transformations several ketones proved unsuitable (Scheme S1 in Supporting Information File 1). Additionally, attempted [4 + 1]-type cycloadditions of three 1-arylprop-2-en-1-ones

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• purification. The synthetic utility of the prepared tetronic acids was demonstrated by further transformations at the hydroxyethylidene fragment. The structures of one obtained tetronic acid and one product of derivatization were confirmed by X-ray analysis. Keywords: allomaltol; base-promoted recyclization

• -hydroxypyran-4-ones these products are widely used in organic synthesis [17][18][19][20][21][22][23]. Among the diverse chemical transformations of allomaltol derivatives the recyclizations of the pyranone ring are of great interest. As a rule, such reactions are realized under action of nitrogen-containing

• nucleophiles and open access to a large array of substituted pyridin-4-ones. Various conditions and reagents employed for these transformations are presented in numerous papers [24][25][26][27][28][29]. Besides that, approaches to the synthesis of pyridazinones and pyrazoles based on the interaction of 3