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

• −), respectively (Scheme 1a). Despite these advances, the above methods still suffer from several limitations, including a narrow substrate scope, the reliance on expensive metal catalysts and excess additives, and the need for multistep synthesis of difluoromethylating reagents. These drawbacks restrict their

• -effectiveness, position it as a valuable strategy in drug design and the synthesis of fluorinated compounds. Selected examples containing tricyclic imidazole, CF2H or PhCF2 group. Strategies for the synthesis of difluoromethylated and difluoroarylmethylated tricyclic imidazoles. Substrate scope of the protocol

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• hydroamination and temporary protection of nitrile and phenolic hydroxy groups. The synthetic strategy enabled the efficient synthesis of the substructure of saframycins bearing isoquinoline and THIQ units in just four steps from the modular assembly of the three components. We also found the unexpected

• cyclization to efficiently construct the pentacyclic intermediate 7, as demonstrated in our previous study [15]. Following the pioneering total synthesis of saframycin A (1) by Fukuyama and co-workers taking advantage of the compatibility of phenolic hydroxy groups with PS-type cyclization [22], other groups

• led by Corey [23], Myers [24][25], Liu [26][27], and Saito [28] also efficiently exploited PS-type reactions to accomplish the total synthesis of saframycin A (1) (Scheme 1b) [3][4][5][29][30][31][32][33][34][35][36][37][38][39][40][41]. However, PS-type reactions impose constraints due to the

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• convergent chemistry characterized by diversity, complexity and efficiency. MCRs are compatible with C1 chemistry due to the generally great tolerance of different functional groups. They have been mostly employed in the synthesis of oxazolidinones and oxazinanones utilizing CO2 and CO [4][16][17][18][19][20

• , they are used in a variety of commercially available drugs (Figure 1). Results and Discussion Design and strategy We envisioned applying the Niementowski quinazoline synthesis [25][39][40][41] (Scheme 1A) by employing three different heterocyclic systems as precursors, which have both an orthogonally

• utilized numerous times in medicinal chemistry campaigns as hits, leads and eventually even drugs, such as 2-aminothiophenes, -quinolines and -indoles [42][43][44][45]. Synthetic exploitation The synthesis of the key cyanoacetamide building blocks was our primary objective. In a parallel setup, a variety

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

• amidation Recently, Cao and co-workers reported the copper-catalyzed synthesis of 1,2,4-triazole derivatives via an N-acyl nitrene intermediate [76]. As illustrated in Scheme 3, dioxazolones 4 and N-iminoquinolinium ylides 5 served as reactive substrates, leading to the formation of various polycyclic 1,2,4

• -triazole analogues 6. Both dioxazolones 4 and N-iminoquinolinium ylides 5 demonstrated excellent tolerance in this transformation. Notably, electron-rich dioxazolones exhibited slightly higher reactivity. The proposed catalytic cycle for the copper-catalyzed synthesis of 1,2,4-triazole derivatives is

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

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

• approach to complex molecule synthesis. Despite considerable efforts to develop various catalytic systems, the activation of aromatic C–F bonds often requires high temperatures [1][2][3][4][5][6][7]. Therefore, methods for activating aromatic C–F bonds at ambient temperature remain underdeveloped. We have

• for the late-stage transformation of C–F bonds, as demonstrated by the orthogonal activation of both aromatic C–F and C–Br bonds, thereby facilitating the synthesis of complex 2-arylbenzofurans. Given that natural and synthetic 2-arylbenzofurans often exhibit considerable biological activities and are

• , 1255, 1163, 1053, 991, 935, 789, 690 cm–1; HREIMS m/z: [M]+ calcd for C19H14O, 258.1045; found, 258.1035. C–F bond activation through β-fluorine elimination via metalacyclopropanes. Synthesis of 2-arylbenzofurans 3 via the coupling of 1 with 2. Isolated yields are given. aNi(cod)2 (10 mol %), PCy3 (20

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

• Venezian 21, 20133, Milano, Italy 10.3762/bjoc.21.7 Abstract This review reports the achievements in copper(II) triflate-catalyzed processes concerning the multicomponent reactions, applied to the synthesis of acyclic and cyclic compounds. In particular, for the heteropolycyclic systems mechanistic

• ; heteropolycycles; multicomponent reactions; one-pot reaction; Introduction Copper has gained a relevant role in organic synthesis as an alternative to precious metals due to its low toxicity, ease of handling, high catalytic activity, and cost-effectiveness [1][2]. In recent years, Cu(OTf)2 has significantly

• 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

• becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• ; Introduction Stereoselective catalytic formation of chiral compounds is one of the critical tasks of modern organic synthesis [1]. The catalytic formation of compounds with a center of chirality has been the focus of countless works and can now be considered a matured area. On the other hand, the generation of

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

• properties. Moreover, these materials offer versatility in their synthesis, allowing for the incorporation of various building blocks to tailor the polymers to desired specifications. Additionally, they lend themselves well to the synthesis of block copolymers, further expanding their potential applications

• would improve the effectivity of the osmotic pressure applied up to a certain point, after which the membrane would be too rigid for deformation. Within this window it is expected that stomatocytes could be obtained using PSar-PBLG block copolymers. Results and Discussion Starting with the synthesis of

• the PSar-PBLG that was used for all the following systems, it was found that a polymer with a length of 50 units sarcosine and 40 units benzyl glutamate would be able to form vesicles between 300–700 nm (Supporting Information File 1, Figure S22). The synthesis of PSar-PBLG (Scheme 1) involved anionic

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• Aalborg, Denmark current address: Centre for Analysis and Synthesis, Lund University, Naturvetarvägen 14, 223 62 Lund, Sweden 10.3762/bjoc.21.4 Abstract Phenethylamines and phenylisopropylamines of scientific relevance can be prepared with a NaBH4/CuCl2 system in 10 to 30 minutes via reduction of

• crucial role in the synthesis of phenethylamine analogues via this method. Dithering before the addition of the copper solution leads to the formation of Micheal adducts, which decrease the product yields. This phenomenon is due to the nature of β-nitrostyrenes, displaying considerable delocalization

• reductive methods used to date for the synthesis of substituted phenethylamines from their α,β-unsaturated nitroalkene analogues. Furthermore, the NaBH4/CuCl2 system is effective at reducing nitro and ester functionalities on aromatic structures, while leaving intact benzoic acid, amido- and halogenated

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

• reactors; data processing; high-throughput experimentation; machine learning; reaction optimization; Introduction Organic synthesis plays a crucial role in drug discovery, polymer synthesis, materials science, agrochemicals, and specialty chemicals. Their synthesis and process optimization require

• substantial resources and are labor-intensive, often exploring only a single variable in search of the optimal conditions while disregarding the intricate interactions among competing variables within the synthesis process. The complexity of the problem requires consideration that process optimization often

• demands solutions that meet multiple targets, such as yield, selectivity, purity, cost, environmental impact, etc. In recent years, the advancement of artificial intelligence (AI), machine learning (ML), and automation has produced a paradigm shift for chemical synthesis optimization techniques. By

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• the best. We look in awe at the achievements in the field to date, some of those appearing in the previous thematic issues “GlycoBioinformatics” [6] and “Synthesis in the glycosciences” I and II [7][8]. We look ahead, asking the question how we can implement new chemistry, new molecules, and new

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• Abstract The polycyclic skeleton of tris(4,5-dehydro-2,3:6,7-dibenzotropone) is a key structural fragment in carbon schwarzites, a theoretical form of negatively curved carbon allotrope. This report presents a new synthesis of this compound using a Ni-mediated Yamamoto coupling reaction and structural

• , expanding its π-skeleton through the Barton–Kellogg and Scholl reactions led to the successful synthesis of a curved polycyclic arene containing three heptagons and two pentagons. Keywords: carbon schwarzites; polycyclic arenes; Scholl reaction; seven-membered carbocycle; Yamamoto coupling; Introduction

• approach to carbon schwarzites requires synthesizing of new negatively curved polycyclic arenes and expanding them to lager three-dimensional molecular nanocarbons. Compound 1 was recently used as a starting material for the synthesis of nonplanar polycyclic arenes, in particular, molecular models of cubic

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• access to PhFlOP-based TADF emitters. Additionally, the design of TADF emitters with the PhFlOP acceptor moiety and the carbazole donor moiety is lacking structural diversity. Herein, we present a 5-step synthesis of several novel D−A−D-type PhFlOP derivatives with substituted carbazole groups as donors

• , starting from commercially available 2-bromo-4-fluoro-1-nitrobenzene under noble-metal-free conditions. The structures and photophysical properties of the desired molecules were also determined. Results and Discussion Synthesis and structural characterization The synthesis of the PhFlOP-based compounds 7

• hand, we turned our attention to the synthesis of PhFlOP-based compounds through a Cs2CO3-facilitated nucleophilic substitution with substituted carbazoles as the nucleophiles (Scheme 2). For example, tert-butyl, bromo, carbazolyl, or phenyl substituents were introduced into the carbazoles. To our

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

• access polyoxygenated benzo[j]fluoranthenes, which are all structurally relevant to benzo[j]fluoranthene-based fungal natural products. The effectiveness of our strategy was demonstrated via a concise, four-step synthesis of the tetramethoxybenzo[j]fluoranthene derivative 18, which represents a formal

• total synthesis of the fungal natural product bulgarein. Keywords: acenaphthylene-fused heteroarenes; benzo[j]fluoranthenes; C–H arylation; fluoranthenes; heterocycles; Introduction An important subclass of polycyclic aromatic hydrocarbons (PAHs) [1] is comprised of fluoranthenes, which have been the

• from certain plant species (Figure 1) [12]. The acenaphthylene-fused thiophene-based heteroarene 3 is another heterocyclic fluoranthene analogue, which was used as an organic semiconductor in transistors [13]. The synthesis and coordination complexes of the acenaphthylene-fused N-heterocyclic (NHC

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

• . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used

• first report from Zhdankin and co-workers in 1994, described the preparation of azidobenziodoxolone, ABX (I), a reagent widely used in oxidative azide transfer reactions [21]. Years later, Zhdankin’s group also reported the synthesis of amidobenziodoxolone (II) [14]. Other examples of N-containing

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• tuneability of the optical and electronic properties, which can potentially be exploited for advanced applications in display technologies, photonic devices, sensors, and organic electronics. We recently successfully reported the straightforward synthesis of several mesogens containing four lateral aliphatic

• increase their structural and functional diversity. In the modern organic synthetic tool-box, the fluoroarene nucleophilc substitution (SNFAr) reaction possesses many outstanding advantages in the synthesis of π-conjugated functional molecules: the electrophiles are plentiful and include cheaply available

• reported the high versatility of these intermolecular interactions in the design of several Janus-like discotic mesogens (Figure 1) [44][45][46][47]. A first study dealt with the synthesis of two sets of compounds, namely 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes (4F-TPn) and 9,10,11,12,13,14

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• [30][31][32]. We herein report the palladium-catalyzed intramolecular C–H arylation of several pyridine and non-pyridine amides to afford multiply fused heterocyclic compounds. Results and Discussion First, we started with the synthesis of the cyclization precursors 1a–c that was carried out by the

• afford 8b in 89% yield under similar conditions, in which the result of carbocyclic amide (7a vs 7b) contrasted with the case of heterocyclic ones, 1c vs 3 and 5a vs 5b. Conclusion We have shown the facile synthesis of fused nitrogen-containing heterocycles and extended the scope of the intramolecular

• palladium catalyzed C–H arylation to pyridine derivatives. The cyclization reaction proceeded in a moderate to excellent yield when an appropriate phosphine ligand was employed. The reaction is expected to be useful for the synthesis of functional materials, and bioactive molecules in a facile manner

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

• enables the synthesis of structurally distinct cyclic derivatives which are difficult to access by other methodologies, using an efficient and atom-economical path from simple precursors. In recent years several asymmetric catalytic cyclization strategies have been accomplished for the construction of N

• construction of carbon–carbon bonds [5][6][7][8][9][10]. The hetero-Diels–Alder reaction is therefore an attractive strategy for the synthesis of heterocyclic compounds. It involves the reaction of dienes or dienophiles which possess a heteroatom in their structure. In this reaction, the HOMO of the diene and

• leading to the synthesis of spirooxindole derivatives 6 bearing a thiourea moiety in high yields (91–97%), and with good to excellent diastereoselectivities (10:1–20:1 dr) and enantioselectivities (61–96%) (Scheme 2). Furthermore, the authors also investigated the reactivity of ketimines and dienimines

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• derivatives exhibit a range of bioactivities, including antibacterial, anticancer, antimalarial, and antiviral effects. Since the discovery of the first psammaplysin derivative, psammaplysin A [4][5], these alkaloids have been recognized as challenging targets for total synthesis. The absolute configuration

• , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• . Ianthelliformisamine D (4) contains a rare N-(3-aminopropyl)-2-pyrrolidone moiety only found in <30 natural products. Owing to the novelty of compound 4, we undertook the first total synthesis of this natural product, which was achieved in three steps. Keywords: ianthelliformisamine; marine sponge; natural products

• ; Pseudomonas; Suberea; total synthesis; Introduction The marine environment covers over two thirds of the earth’s surface and it encompasses a wide range of complex ecosystems that are highly variable in their physical attributes including pressure, salinity, temperature, and light availability. Both flora

• activity against both Pseudomonas aeruginosa and Staphylococcus aureus, has contributed to a surge in the interest of polyamines as new antibacterial leads [6]. To date the total synthesis of ianthelliformisamines A–C (1–3) has been described [7] and numerous synthetically related analogues have been

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

• 10.3762/bjoc.20.265 Abstract We report the synthesis of germanyl triazoles formed via a copper-catalysed azide–alkyne cycloaddition (CuAAC) of germanyl alkynes. The reaction is often high yielding, functional group tolerant, and compatible with complex molecules. The installation of the Ge moiety enables

• established as a powerful approach for molecule synthesis. Strategies within click chemistry include several widely used reactions such as the (hetero-)Diels–Alder reaction [1][2], alkene hydrothiolation [3], and an array of amide-bond-forming chemistries [4]. However, by virtue of the access to alkyne and

• potential as functional handles for downstream elaboration of CuAAC products. To date, the main use of germanyl alkynes in (3 + 2) cycloadditions has been limited to a small number of Huisgen (non-Cu-catalysed) reactions [68][69]. Zaitsev and co-workers reported the synthesis and CuAAC reactions of a

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

• -carboxylic acid derivatives are not only valuable synthetic building blocks [3][4][5][6][7][8][9][10][11] but also show useful biological activities [12][13][14][15][16][17][18]. Although many 2,2-bifunctionalized azirines have been synthesized [3][4][5][6][7][8][9][10][11], the synthesis of only one 2H

• -azirine-2,2-dicarboxylic acid derivative, dimethyl 3-phenyl-2H-azirine-2,2-dicarboxylate, has been reported to date. This compound was prepared by a Rh2(Piv)4-catalyzed isomerization of methyl 5-methoxy-3-phenylisoxazole-4-carboxylate [19]. The described linear synthesis, unfortunately, allows obtaining

• only one azirine-2,2-dicarboxylic acid derivative from a certain isoxazole precursor. Herein, we would like to report a method for the synthesis of 2H-azirine-2,2-dicarboxylic acids and their various derivatives from a single starting material, 3-substituted 2H-azirine-2,2-dicarbonyl dichloride 2, via

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

• 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

• ) hypervalent iodonium salts, for the efficient synthesis of fluorinated sulfoxonium ylides (Scheme 1c). Results and Discussion Since the introduction of hypervalent iodonium salts in organic chemistry, these valuable reagents have led to many new strategies for carbon–carbon bond formation [31][32]. Our

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

• synthesis of tripeptides incorporating new fluorinated heterocyclic hydrazino acids, based on the tetrahydropyridazine scaffold is described. Starting from simple fluorinated hydrazones, these non-proteinogenic cyclic β-amino acids were easily prepared by a zinc-catalyzed aza-Barbier reaction followed by an

• ; Introduction The synthesis of molecules capable of mimicking the various secondary structures and key functions of proteins is a major challenge in medicinal chemistry, especially in the fields of protein–protein interactions [1][2]. Accordingly, the incorporation of heterocyclic amino acids into peptides

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing