Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• these sulfones with epoxides 23b and 23a, respectively. Following the literature procedure for a similar reaction, using n-butyllithium in the presence of BF3·Et2O at −78 °C, the coupling reaction unfortunately resulted in the decomposition of the reactants (Scheme 4). The authors hypothesized that the

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• yield of 88%. (R)-Methyl 6-oxopipecolate (7) was converted under Vilsmeier–Haack conditions [35][40][41] to undergo N-formylation and concomitant enol bromination to give product 2 (Scheme 2). Due to slow degradation of the bromide 2, the subsequent cross-coupling reaction was conducted immediately

• reduction product 13 of a Sonogashira–Hagihara cross-coupling reaction. This was synthesised under similar conditions as the Suzuki–Miyaura counterpart 3 utilising the same Pd catalyst, base and solvent. In addition, 10 mol % CuI as a co-catalyst and 2.0 equiv phenylacetylene (12) were used, resulting in

• –Miyaura cross-coupling reaction between bromide 2 and a variety of boronic acids 8. Reaction of 3a to (2R,6S)-9a and (2R,6R)-9a. The chromatograms prove the simple diastereoselection. a) Sonogashira–Hagihara cross-coupling reaction followed by b) NaBH3CN reduction of the N-acyliminium species and c

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• multimetal-organic framework (M-MOF, M= Cu, Ni) which successfully catalyzed the one-pot cyclopropenone hydration/Chan–Lam coupling reaction of 309 and boronic acid 341 to give the corresponding ester 310 in good yield via the formation of acid 342 (Scheme 76B). Cyclopropenone was also subjected to non-metal

• ) [131]. In addition, a gram scale operation has been successfully demonstrated. In addition, Hu and co-workers (2020) studied a catalyst-free multicomponent coupling reaction of benzynes derived from alkyne 349, cyclopropenone 309, and sulfoxides to give the corresponding o-(methylthio)phenyl acrylates

• and using ylide 397 altered the stereoselectivity to E-isomeric products 400 and 401 [144]. Wu and co-workers (2020) employed Pd to mediate the cross-coupling reaction of sulfoxonium ylide 402 and benzyl bromides to give the corresponding (Z)-ethyl cinnamates 403–406 in good yields via carbene

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• pyrrolopyrimidine derivatives. The envisioned methodology combines a Sonogashira–Hagihara reaction and a one-pot process comprising a Buchwald–Hartwig coupling reaction followed by a hydroamination [23][24]. Results and Discussion The bromination of 6-chloro-1,3-dimethyluracil (1) afforded, following a known

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• reactions: reduction of ring A of the β-carboline skeleton or trifluoroethylation of the pyrrole moiety occurred, leading to interesting and potentially useful derivatives. Keywords: alkaloid; β-carboline; Carex brevicollis DC; cross-coupling reaction; trifluoroethylation; Introduction Carex brevicollis

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• , which acts as a base. Subsequently, I undergoes oxidative addition and complexation with the amidine 2 to generate intermediate II. This intermediate then undergoes reductive elimination to form intermediate III, releasing CS@CuI back into the system. Finally, the coupling reaction between the carboxyl

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• a subsequent Suzuki cross-coupling reaction with (4-(diphenylamino)phenyl)boronic acid was performed. The reaction conditions were adapted from prior experiments with C-NBD1 [40] and further refined for the heterocyclic analogues. Optimal results were achieved using K2CO3, Pd(OAc)2 and RuPhos with

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• amides with electron-withdrawing or electron-donating groups on their aromatic ring, producing products with yields ranging from 51% to 82%. In 2023, Lei and co-workers [47] reported an electrochemical C–P bond formation via a coupling reaction of C–H bonds of alkynes, alkenes, and aryl compounds with

• dialkyl phosphonates at carbon and platinum electrodes as the anode and cathode in the presence of a silver catalyst in a divided cell (Scheme 3). According to the report, the silver catalyst is central to the coupling reaction. The study of the effect of alternating current (a.c.) electrolysis parameters

• ferrocene and ruthenocene via coupling reaction. This method provides an efficient and versatile synthetic approach for producing phosphorylated metallocenes but also aids in interpreting the regioselectivity and reactivity of C−H functionalization in unsymmetric metallocenes. They used a platinum electrode

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• and excellent yield of 94% (Scheme 1). A chemoselective deprotection of the mannosyl thioacetate 7 to yield the glycosyl thiol 8 was achieved using 0.95 equivalents of sodium carbonate. The crude product was in turn submitted to a Buchwald–Hartwig–Migita cross-coupling reaction [33] with the

• -dithio-ᴅ-threitol) [36] (Scheme 2A). The crude thiol 14 was subsequently subjected to a Buchwald–Hartwig–Migita cross-coupling reaction with the literature-known azobenzene thioglucoside 15 [37], resulting in the (6-thioglucosyl)mannoside 16 in 63% yield over two steps. Zemplén deacetylation [38] gave

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• reaction by metal catalysis is an option to avoid the problems regarding iminium or aminal stability. This is an important issue in AAA coupling when formaldehyde is used as the C1 source. Finally, a later work proposes a catalysis-free protocol for the synthesis of propargylamines by an AHA coupling

• secondary amines such as piperidine or pyrrolidine afford an aminal or an iminium ion, in general under high temperature or pressure conditions, which is not the case for the AHA coupling [69][70]. Despite these cases, the absence of evidence in terms of iminium ion generation confirms that the AHA coupling

• reaction [71]. Here, the reaction is carried out under mild conditions (CH2Cl2, 70 °C) without the need for catalysis or additional base for the activation of C–H and C–X bonds of the alkyne and dihalomethane compounds, respectively. However, this strategy has a limited scope in terms of the alkyne

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• compared to parent diazocine [3][13]. Reaction conditions of the arylation of halogenated N-acetyl diazocines via Stille coupling reaction. Equivalents are normalized to the used amount of N-acetyl diazocine starting material. Vinylation of halogenated N-acetyl diazocines via Pd-catalyzed coupling

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

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

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• reaction at 120 °C for 2 hours were determined as optimal conditions for the reaction (Table 1, entry 14). Under the optimized conditions, the coupling reaction of various sodium arylsulfinates was investigated to assess the scope and generality of this protocol. The results, shown in Scheme 2

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

• -fluorobenzene (see Scheme 2 and Supporting Information File 1 for details). Copper(I)-catalyzed three-component coupling reaction of alkyne 8, THIQ 9, and benzaldehyde, proceeded with exquisite control of regioselectivity to afford 10 in an excellent yield of 92% [43][44][45][46]. This efficient cascade

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

• undergoes reductive elimination to provide the desired enantioenriched nitrile product 111 and Cu(I) catalyst 116. The resulting Cu(I) catalyst 116 is reoxidized to Cu(II) 117 at the anode, completing the catalytic cycle. Coupling reaction (Chan–Lam coupling) Transition metal-catalyzed C–N bond formation

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

• equivalents of 2b to 1.0 equiv and K2CO3 to 1.2 equiv, we achieved the highest yield of 98% for 3bb (Table 1, entry 9). Under the optimized conditions, we investigated the substrate scope using 2-fluorobenzofurans 1 and arylboronic acids 2 (Scheme 2). The coupling reaction was efficient with 2

• optimized the coupling reaction using potassium phosphate as a base and increasing the nickel catalyst loading to 20 mol %, achieving a yield of 78% for the desired product 3bg. When 2-naphthylboronic acid (2i) was employed, its solubility was enhanced using a mixed solvent system of toluene, methanol, and

• , reductive elimination from G yields the coupling products 3. The following experiments were performed to elucidate the mechanism. Under the same conditions as the coupling reaction, stoichiometric amounts of Ni(cod)2, PCy3, and cod were treated with fluoronaphthofuran 1b at room temperature for 13 h

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

• alkyltrifluoroborate into its corresponding alkyl radical. o-Halo-substituted aryl selenides and sulfides 13 can be achieved by a three-component coupling reaction performed with an aryne precursor, potassium halides and electrophilic chalcogen species as reactants, in the presence of Cu(OTf)2 (Scheme 10) [23]. Under

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

• organocatalytic cross-coupling reaction of 1-azonaphthalenes 238 with 2-naphthols 239 catalyzed by chiral N-triflylphosphoramide C56 was done in 2023 (Scheme 70) [104]. A remarkable number of axially chiral products 240 were prepared with excellent enantiomeric purities and high yields. Undiminished yields and

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

• were explored, using a total volume of 4.5 mL reaction mixture, and the screening results can be readily translated to continuous flow synthesis. The application of segmented flow or microslug reactors was demonstrated in the decarboxylative arylation cross-coupling reaction promoted by catalysts and

• drug molecules autonomously, and it does not include a closed-loop optimization framework. The Pfizer research team developed a custom-designed flow system for rapid reaction screening of the Suzuki–Miyaura coupling reaction on a nanomolar scale [50]. The platform included a modified HPLC system that

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

• synthesis of 1 using a Ni-mediated Yamamoto coupling reaction and the simultaneous crystallization of its two different conformers from the same solution. Expanding the π-skeleton of 1 through a Barton–Kellogg reaction followed by a subsequent Scholl reaction resulted in a new polycyclic arene (3 in Figure

• yield of 90%. Then, the Ni-mediated Yamamoto coupling reaction of 6 enabled cyclotrimerization to give trione 1 in a yield of 30%. It is worth mentioning that using 1,10-phenanthroline as the ligand in the Yamamoto coupling [25][26] led to a higher yield of compound 1 than using 2,2’-bipyridine. With

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

• analogues via a Pd-catalyzed reaction cascade that consists of a Suzuki–Miyaura cross-coupling reaction followed by an intramolecular C–H arylation. These heterocyclic fluoranthene analogues include a variety of acenaphthylene-fused heteroarenes such as thiophene, furan, benzofuran, pyrazole, pyridine and

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

• conditions. We carried out the palladium-catalyzed intramolecular coupling reaction of precursor 1a under similar conditions [23], which afforded smooth reaction with phenanthroline bisamide, with 10 mol % of palladium acetate as a catalyst in the presence of potassium carbonate and tetra-n-butylammonium

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

• LiOH, followed by a coupling reaction with ʟ-valine methyl ester hydrochloride, to give the corresponding four enantiomerically pure tripeptides 8 with satisfactory yields over two steps (Scheme 6). The absolute configuration (S,S,S) of the isomer 8f was unambiguously assigned by X-ray crystallographic

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• . Results and Discussion The norbornadiene derivatives 1h–l,n were synthesized by Sonogashira–Hagihara coupling reaction of 2-bromonorbornadiene (1g) [36] with the corresponding arylacetylenes 3a–g (Scheme 2). As an exception, 1,4-bis-norbornadienylnaphthalene (1m) could not be obtained by this route