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

• reaction involves an in situ generation of the iminium cation A followed by isomerization to the thermodynamically more stable iminium cation B. Subsequent nucleophilic attack of a copper acetylide enabled regioselective C–C bond formation at the C11 position. After removal of the cyclic acetal, the

• and a catalytic amount of triethylamine were used in dichloromethane with careful control of the reaction temperature at 15 °C (Table S2, Supporting Information File 1). With the 2,3-diaminobenzofuran 11 in hand as the designed cyclization precursor, we explored the construction of the left

• isoquinoline ring via gold(I)-mediated 6-endo hydroamination (Scheme 2). Treatment of 11 with a cationic gold complex, generated in situ from AuCl(PPh3) and AgNTf2 [47][48][49][56], with an excess amount of triethylamine in 1,2-dichloroethane at 65 °C, resulted in the intended regiocontrolled hydroamination

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

• . 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

• potential bioactivity [70][71][72][73]. Despite the development of synthetic approaches for six-membered lactams, including transition-metal-catalyzed transformations, several limitations remain, particularly with regard to regioselectivity and asymmetric C–N bond formation, which are still limited. In 2023

• , the Chang group elegantly unveiled a protocol for an enantioselective C–N bond formation, introducing δ-lactams from dioxazolones using a copper(I) catalyst and a chiral BOX ligand [74]. As shown in Scheme 2, dioxazolones containing aryl and heteroaryl groups were converted into the corresponding

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• 1H NMR chemical shift change, thereby allowing the interactions of individual HB donating moieties with n-Bu3PO to be probed (Figure 4B and C). Moreover, we used anhydrous deuterated acetonitrile (CD3CN) as the solvent, in which both neutral and ionic compounds exhibited appreciable solubility. In

• constructs. Although many of the CF2H HB donors studied here can promote relatively strong hydrogen bonding interactions with n-Bu3PO, even the strongest CF2H HB donor (3b) is still 30 times weaker than phenol (10), corresponding to about a 2 kcal/mol reduction in binding energy at 25 °C. These results

• reveal the fundamental differences between the C–H bond and the O–H bond as HB donors and provide important quantitative information for applying the CF2H group as an OH group mimic. We next attempted to establish correlations of experimentally determined HB donation ability, in terms of Kd or ΔGexp

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• strict 2:2 molar ratio (Figure 3), providing convincing evidence for the dimerization process. The complex crystallized in the monoclinic P2(1)/c space group with lattice constants a = 24.434(4) Å, b = 20.026(3) Å, and c = 23.779(4) Å. The dimeric superstructure was stabilized by multiple cooperative

• noncovalent interactions, particularly intermolecular π–π-stacking and C–H···O interactions. Specifically, π–π-stacking interactions were found between two guest molecules with aromatic rings arrayed in an offset fashion with a distance of 3.3 Å (Figure 3a). Interestingly, these interactions also existed

• /or π-stacking interactions, conferring the characteristic 2:2 constitutional stoichiometry onto this host–guest complex. In addition, there were eight C–H···O interactions between the hydrogen atoms of G1 and the nearby pyridinium group of H2, with distances of 2.2–3.5 Å, and two C–H···O interactions

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

• chemistry. Combining electrochemistry with transition-metal catalysis is a promising and rapidly growing methodology for effectively forming challenging C–C and C–heteroatom bonds in complex molecules in a sustainable manner. In this review, we summarize the recent advances in the combination of

• 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

• –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

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

• , Ibaraki 305-8571, Japan Sagami Chemical Research Institute, 2743-1 Hayakawa, Ayase, Kanagawa 252-1193, Japan 10.3762/bjoc.21.8 Abstract 2-Fluorobenzofurans underwent efficient nickel-catalyzed coupling with arylboronic acids through the activation of aromatic C–F bonds. This method allowed us to

• coupling reactions of aromatic C–F and C–Br bonds with arylboronic acids. Keywords: arylboronic acid; benzofuran; C–F bond activation; cross-coupling; nickel; Introduction The metal-catalyzed activation of aromatic carbon–fluorine (C–F) bonds is widely recognized as a challenging task in synthetic

• organic chemistry owing to their high bond dissociation energy compared to other aromatic C–X (X = Cl, Br, I) bonds [1][2][3][4][5][6][7]. This activation is essential for the late-stage functionalization of stable C–F bonds in complex molecules with reactive functional groups, providing an orthogonal

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

• to multiple C–C bonds generates extended carbon radicals capable of giving further functionalization. Regarding the ionic mechanism, the key step generally comprises the complexation with the unsaturated substrate leading to activation of the alkenyl/alkynyl moiety towards a nucleophilic attack. In

• some cases, activation of a carbonyl group by the copper catalyst to facilitate nucleophilic attack has also been reported. Moreover, both activations can be operative simultaneously. Since copper shows affinity either for multiple C–C bonds or polar functional groups, it seems the ideal tool for this

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

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

• structural motifs [13][14][15][16][17]. Remarkably, these compounds are not limited to the C(sp2)–C(sp2) axis, but new developments in the formation of C–N, C–B, or even N–N stereogenic axes have been achieved. To help the research community distill and abstract the relevant new knowledge, this review has

• NBS and AgOTf led to the formation of the (Sa)-atropoisomers, whereas NIS afforded the (Ra)-atropoisomers. Non-biaryl atropoisomers are characterized by at least one non-aryl substituent on the stereogenic axis. Among them, compounds featuring a conformationally stable C(sp2)–C(sp3) stereogenic axis

• followed by lactonization to Int-21 and Int-22 (Scheme 11c). Chi and co-workers showed that desymmetrization of urazoles can lead to axially chiral derivatives [31]. The NHC-catalyzed (3 + 2) annulation between α,β-unsaturated aldehydes 36 and urazoles 37 generates atropoisomers 38 with a C–N stereogenic

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

• was determined using differential scanning calorimetry (DSC) (Supporting Information File 1, Figure S18). The results revealed a Tg of approximately 100 °C for PSar-PBLG, indicating the potential for shape locking through transitions between fluidity and a glassy state. Additionally, examination of

• the thermogram unveiled a peak during the initial heating cycle, spanning from 40 °C to 90 °C (Supporting Information File 1, Figure S18). This peak corresponds with the dehydration temperature of polysarcosine, suggesting its role in facilitating subsequent shape manipulation [16]. The assembly of

• raising the temperature influences most of these parameters, reducing permeability and increasing membrane stiffness due to enhanced sarcosine chain interactions [16]. Heating the sample to 70 °C and then applying osmotic shock through PEG addition, followed by quenching with water, transformed the shape

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

• ), and appetite suppressants (e.g., phentermine) [6]. Phenethylamines can be produced via numerous different procedures [7]. One of the oldest methods involves the reduction of benzyl cyanide with H2 in liquid ammonia with Raney-Nickel catalyst at 130 °C, and high pressure [8]. Another known method is

• to synthesize phenethyl- and phenylisopropylamines from the corresponding nitroalkenes [15][17]. Representatively substituted β-nitrostyrene analogues were reduced via this method at 80 ˚C, including 2,5-dimethoxy-β-methyl-β-nitrostyrene (3a), precursor of amphetamines, and 2,5-dimethoxy-β

• stirring with minor yield loss. Increasing the heating temperature up to 110 °C does not lead to increased product yields (for more information on the optimization process, see Supporting Information File 1, page S19). The use of diethylenetriamine (DETA) was also investigated to evaluate its impact on the

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

• various reaction categories. The system consists of a liquid–liquid separator and an in-line/online analytical tool to facilitate closed-loop autonomous optimization. The capability of the system was demonstrated in the optimization of C–C and C–N cross-coupling, olefination, reductive amination

• , utilizing a custom Python package developed in-house [53]. This approach enabled us to track the conversion process at different residence times. Specifically, we quantified the conversion by analyzing the area under the curve (AUC) of the Raman-active vibrational modes associated with the styrene–vinyl C=C

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

• -tropone” in literature [1][2], although it should be named as 9H,18H,27H-hexabenzo[c,c′,c′′,f,f′,f′′]benzo[1,2-a:3,4-a′:5,6-a′′]triscycloheptene-9,18,27-trione according to the IUPAC nomenclature. We became interested in compound 1 because its polycyclic skeleton presents a key structural unit in carbon

• synthesized according to the procedures detailed in Supporting Information File 1. In this reaction, the first step of diazo–thioketone coupling occurred at 50 °C in THF, and the second step of desulfurization with triisopropyl phosphite occurred in refluxed toluene, giving diene 10 in a yield of 47%. The

• room temperature yielded partially fused nanographene 3 (20%), with formation of six C–C bonds giving four six-membered rings and two five-membered rings. Performing this reaction at a higher temperature led to a lower yield of compound 3 and the formation of byproducts with lower Rf values on thin

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

• delight, by treatment of 5 with substituted carbazoles 6 in the presence of Cs2CO3 (5.0 equiv) in DMF at 100 °C, seven 2,8-bis(9H-carbazol-9-yl)-5-phenylbenzo[b]phosphindole 5-oxide derivatives 7 were furnished in good to excellent yields (77–91%). The structural characterization of the obtained molecules

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

• %). This cascade involves an initial Suzuki–Miyaura cross-coupling reaction between 1,8-dihalonaphthalenes and heteroarylboronic acids or esters, followed by an intramolecular C–H arylation under the same conditions to yield the final heterocyclic fluoranthene analogues. The method was further employed to

• 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

• -based natural product, which was discovered to induce topoisomerase I-mediated DNA cleavage [16][17]. For the construction of the fluoranthene skeleton, a broad range of synthetic strategies including C–H arylation [18][19][20][21][22], Diels–Alder [7][8][23][24][25] and [2 + 2 + 2] cycloadditions [26

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

• Beatriz Dedeiras Catarina S. Caldeira Jose C. Cunha Clara S. B. Gomes M. Manuel B. Marques LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA FCT , 2829-516 Caparica, Portugal 10.3762/bjoc.20.272 Abstract The reactivity of our recently disclosed hypervalent iodine

• as strong oxidizing agents [1], during the last decades HIRs have been investigated as group-transfer reagents, useful in several bond-forming reactions, such as in C–C, C–N, and C–O [2][3][4][5]. The benziodoxol(on)e family, cyclic iodine(III) reagents, stands out for their thermal stability and

• benziodoxolone, 2d) were obtained with quantitative yields, as white solids on the gram-scale, easy to manipulate and long-term stable below 0 °C. Crystals of compound 2d were successfully obtained and its molecular structure was confirmed through single-crystal X-ray diffraction. The X-ray analysis revealed a

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

• , forming a new C(sp3)–C(sp3) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry. Keywords: dehydroalanine; Giese-type reaction; hydroalkylation; photocatalysis; water

• ; Introduction The construction of C(sp3)–C(sp3) bonds is a highly important target in synthetic organic chemistry. Historically, polar conjugate additions have been a benchmark method for constructing these bonds by functionalizing an electron-deficient olefin [1][2][3]. Recently, however, radical-based

• )silane and a substoichiometric amount of (4-methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone (BP l) (Table 1) [26][27]. The reaction was performed in batch, using a 390 nm Kessil UV-A lamp, stirring at 600 rpm overnight at 25 °C (see Supporting Information File 1 for a more detailed optimization). The

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

• commercial perfluoroarene chemical blocks and reagents, involving catalyzed C–F-bond activation and cross-coupling reactions, usually requiring precious transition-metal catalysts and tedious synthetic routes [28][29][30][31][32][33][34]. Therefore, low-cost and facile synthetic strategies are desired to

• the Janus Fn derivatives exhibit a hexagonal columnar liquid crystal phase (Colhex), with clearing temperatures decreasing gradually with the elongation of the alkoxy side-chains, from nearly 200 °C for the shortest homologs down to ca. 100 °C for the dodecyloxy derivative. The larger lath-like

• compounds, Gnm, exhibit a rectangular columnar phase (Colrec) also over large temperature ranges from ambient up to 183 and 164 °C, respectively. The unsymmetrically alkoxy-substituted derivative, G48, also displays a Colrec over a similar temperature range. The compounds’ photophysical properties have also

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

• Abstract The C–H arylation of 2-quinolinecarboxyamide bearing a C–Br bond at the N-aryl moiety is carried out with a palladium catalyst. The reaction proceeds at the C–H bond on the pyridine ring adjacent to the amide group in the presence of 10 mol % Pd(OAc)2 at 110 °C to afford the cyclized product in 42

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

• ; phosphine ligand; pyridine amides; Introduction Transition-metal-catalyzed synthetic reactions have recently attracted much attention in synthetic organic chemistry [1][2]. C–H Arylation reactions catalyzed by a transition metal are of particular interest because these reactions involve rather superior

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

• (Scheme 3). The reaction of 3-isothiocyanatooxindoles 4 and ketimines 7 led to the (3 + 2) cycloaddition through the C=C bond of the α,β-unsaturated imine instead of the C=N bond, affording various spirocyclic derivatives 8 with excellent yields (92–98%), diastereoselectivities (15:1–20:1 dr), and

• alcohol E isomer and it coordinated to the squaramide in an effective orientation, a stepwise mechanism is taking place. Firstly, the dienolate adds to the azadiene which is followed by cyclization with formation of the C–N bond. Finally, protonation leads to the formation of the desired derivative. The

• alternative pathway which occurs is the transformation of the α,β-unsaturated imine into the corresponding enamine C, which attacks to the azlactone leading to the addition subproduct 49’, also observed in the catalytic reactions. Also in 2020, Lu and co-workers reported an enantioselective dearomatization of

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

• (partial structures a and b, respectively, in Figure 2), which were characteristic of psammaplysins, in ceratinadin G (1) was suggested by comparison of its 1H and 13C NMR data with those of known psammaplysin derivatives such as psammaplysins A and F (2) [4][5][6][10][11][12]. HMBC correlations (H-1/C-2

• , H-1/C-3, H-1/C-6, H2-5/C-3, H2-5/C-4, H2-5/C-6, H-5a/C-7, H-7/C-8, and 3-OCH3/C-3) supported the presence of the 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol unit (partial structure a in Figure 2). While the existence of the 11-N-methylmoloka'iamine unit (partial structure

• b in Figure 2) was confirmed by the 1H-1H COSY and TOCSY correlations (C-10–C-12 and C-19–C-20), and HMBC correlations (H2-12/C-13, H-15/C-14 (H-17/C-18), H-15/C-19 (H-17/C-19), H-17/C-13 (H-15/C-13), H-17/C-15 (H-15/C-17), and H2-20/C-16). HMBC correlations between the N-methyl protons H3-21 (δH

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

• , Don Young Road, Brisbane, 4111, Australia 10.3762/bjoc.20.266 Abstract The marine sponge Suberea ianthelliformis was investigated for new chemistry after the recent discovery that polyamines ianthelliformisamines A–C (1–3) – originally sourced from this Australian sponge – act as Pseudomonas

• ], therefore it is no surprise that sponges are highly sought after for novel bioactive metabolites and have been a major focus of marine natural product drug discovery for over 70 years. The identification of ianthelliformisamines A–C from the Australian marine sponge Suberea ianthelliformis, which displayed

• 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

• proven useful in various Cu- and Pd-catalysed C–X-bond-forming strategies [43][44][45][46][47][48][49][50][51], including widespread use across several CuAAC methodologies [52][53][54]. Germanium-based functional groups have recently emerged as highly useful components for transition-metal-catalysed

• 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

• ) Functionalisation of germylated triazoles. Isolated yields unless stated. (i) Pd(PPh3)4 (10 mol %), 2-bromothiazole (1.2 equiv), KCl (3.0 equiv), PhMe/EtOH 4:1, N2, 100 °C, 16 h. NMR yield in parentheses. (ii) Pd2(dba)3 (2.5 mol %), iodobenzene (1.5 equiv), AgBF4 (1.5 equiv), DMF, N2, 80 °C, 16 h. (iii) NBS (2.0

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

• included oxidation of aldehydes 4 with Oxone to acids 5 and the conversion of the latter into acid chlorides with thionyl chloride. The first reaction sequence was suitable for obtaining compounds 1a–c,e,f with substituents tolerant to radical reaction conditions. A significant advantage of the method is

• complex, which facilitates the cleavage of the N–O bond and subsequent 1,3-cyclization, ultimately leading to the formation of 2H-azirine. Therefore, the isomerization of isoxazole 1j was carried out at a higher temperature, 82 °C, but after hydrolysis of the reaction mixture, instead of the expected

• because the isomerization of 3-(tert-butyl)-5-chloroisoxazole-4-carbonyl chloride did not occur at room temperature, but at elevated temperature (82 °C) the reaction proceeded via the formation of the nitrile ylide, which cyclized to 2-(tert-butyl)-5-chlorooxazole-4-carbonyl chloride. 3-Phenyl-2H-azirine

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

• Radell Echemendia Carlee A. Montgomery Fabio Cuzzucoli Antonio C. B. Burtoloso Graham K. Murphy São Carlos Institute of Chemistry, University of São Paulo, 13560-970, São Carlos, SP, Brazil Department of Chemistry, University of Waterloo, 200 University Ave W., Waterloo, Ontario, Canada

• ]. 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

•  1, entries 9–12). We attempted to decrease the reaction time by increasing the temperature, but these changes resulted in decreased yields of 3a (Table 1, entries 13 and 14). Surprisingly, when using microwave (MW) heating at 70 ⁰C for 10 min in ACN, product 3a was formed in 74% yield (Table 1

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

• , Tomilov et al. described the formation of tetrahydropyridazine 3,4,5,6-tetracarboxylic esters in 42% yield upon the decomposition in chloroform at 60 °C of methyl diazoacetate in the presence of pyridine and catalyzed by rhodium(II) acetate (Scheme 1b) [24][25]. More recently, an unusual [4 + 2