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

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

• to be altered sufficiently to evoke a noticeable improvement of the ϕ [48]. This also holds true for mono-para-substitution with boronic acid derivatives, yielding λem = 580 nm and ϕ of 1–3% (in dichloromethane) [49]. Substituting one or two of the 2,4,6-trichlorinated rings in TTM with 2,4,6

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

• the corresponding boronic acid in a degassed toluene/H2O mixture (4:1, v/v) which was heated to 80 °C for 18 h (for detailed information see Supporting Information File 1). Using the described procedure, the oxygen containing derivatives O-NBD2 and nitrogen substituted N-NBD2 were successfully

• %; furan, 45 °C, 24 h, 84%; N-Boc-pyrrol, 90 °C, 68 h, 53%; ii) (4-(diphenylamino)phenyl)boronic acid (1.2 equiv), K2CO3, Pd(OAc)2, RuPhos, 4:1 toluene/H2O, 80 °C , 18 h. Overview of the new NBD derivatives and the isomerization products (QCs) expected upon isomerization. Formation of N-QC1 and N-QC2 could

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

• with bis(pinacolato)diboron did not lead to the formation of the pinacolborane-substituted N-acetyl diazocine 18. Accordingly, the Suzuki–Miyaura reaction with inversed roles between N-acetyl diazocine boronic acid pinacol ester and aryl or alkyl halides could not be investigated. The Buchwald–Hartwig

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

• boronic acid and disproportionation. Subsequently, the coupling product 120 is released through reductive elimination, and the resulting Cu(I) species 121 is either reoxidized or plated on the cathode. Despite the success of electrochemical Chan–Lam coupling for C–N bond formation, the electrooxidative

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

• distinct aryl groups onto a benzofuran ring through orthogonal coupling reactions, exploiting the reactivity difference between C–F and C–Br bonds (Scheme 4). Using a palladium catalyst, 5-bromo-2-fluorobenzofuran (1e) was coupled with [4-(trifluoromethyl)phenyl]boronic acid (2g). In this reaction, only

• , excluding boronic acid 2a (Scheme 6). The reaction was monitored using 19F and 31P NMR spectroscopy. The 19F NMR analysis showed that 79% of 1b remained and revealed a new broad double doublet peak at 55.0 ppm (JFP = 53, 42 Hz) relative to internal C6F6 (δ = 0.0 ppm). The 31P NMR spectrum depicted broad

• : X = I) with (3-methylphenyl)boronic acid (2b) (Table 2). Both 2-chlorobenzofuran (1a-Cl) and 2-bromobenzofuran (1a-Br) hardly yielded 3ab under the optimized conditions for 1a (Table 2, entries 2 and 3), while the reaction of 2-iodobenzofuran (1a-I) resulted in a much lower yield (32%) of 2

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

•  1 demonstrate that a variety of thiopheneboronic acid and esters are competent substrates in our fluoranthene synthesis methodology. Following the successful results with the use of thiophene boronic acid and esters, we next investigated the scope of our methodology to prepare a variety of other

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

• %, Table 2, entry 4). Afterwards, we sought to examine the reactivity of six-membered aromatic nitrogen heterocycles. The reactions of (2-methoxypyridin-3-yl)boronic acid with the dihalonaphthalenes 12 and 14 afforded substituted azafluoranthenes 15f and 15g in 90 and 51% yields, respectively (Table 2

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

• development as a therapeutic agent for AD. Petasis reaction: Continuing in the context of the development of MTDLs, in 2023 Madhav et al. [40] reported the synthesis of pyrazine-based MTDLs using the Petasis reaction, which involves a secondary amine, a suitable aldehyde, and a substituted boronic acid in the

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• the Suzuki coupling began with investigating first the Suzuki reaction compatibility of boronic acid 14 with porphyrin 13. Porphyrin 13 and phenylboronic acid (14) were subjected to coupling at 85 °C for 48 hours using Pd2dba3/SPhos as a catalyst/ligand giving porphyrin 26 in a 32% yield, based on a

• ). The reaction temperature was increased to 110 °C, affording the desired porphyrin 27 in a 39% yield (Table 1, entry 3). A temperature of 110 °C was also used for the synthesis of terphenylporphyrin 28 using boronic acid 17, affording terphenylporphyrin 28 in 48% yield (Table 1, entry 7). Boronic acids

• with heteroatoms and activating/deactivating electronic properties were investigated next. Attempts to introduce electron-withdrawing groups at the para-position with substrate boronic acid 16a (Table 1, entries 4 and 5) yielded no tetracoupled product. Similarly, coupling with 18a resulted in most of

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

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

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• (PPh3)4 (10 mol %), NaOH (3 equiv), 1,4-dioxane/water 5:1, 100 °C, 1 h; iv) p-TsOH (20 equiv), toluene, 100 °C, 4 h. Synthesis and isolated yields of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 4a–i. Reaction conditions: 3 (1 equiv), boronic acid (1.2 equiv), Pd(PPh3)4 (5 mol %), NaOH (3 equiv), 1,4

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• and 11). We predicted that the product yield would decrease because 2k is labile in column chromatography. Utilizing a boronic acid bearing an n-butyl group as a primary alkyl group (4m), the cross-coupling did not proceed due to β-elimination (Table 3, entry 12). In contrast, the reaction with

• mol %), cesium carbonate (1.5 equiv), palladium bis(trifluoroacetate) (5 mol %) in THF (2.0 mL) was added the respective boronic acid derivative 4 (2.0 equiv). The reaction solution was refluxed for 3.5 h. The reaction mixture was quenched by the addition of water (40 mL) at 0 °C and extracted with

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• arylhydrazines 116 are used as starting materials. The p-bromophenylpyrazoles presented in situ can be reacted with boronic acids or boronic acid esters in a sequentially Pd-catalyzed coupling towards biaryl-substituted pyrazoles 113, 115, and 117 (Scheme 41) [138]. Furthermore, a pseudo-five-component reaction

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• temperature and then, upon addition of the boronic acid, heating at 60 °C (Scheme 9). Similar efficiencies were observed with a wide range of boronic acids (10 examples, 49–87% yield). The biohybrid was suitable also for gram-scale synthesis and for storage at room temperature under inert atmosphere, showing

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• out, resulting in the corresponding N-tosylhydrazones 51a–c. Afterwards, the compounds were subjected to microwave irradiation in the presence of (3-azidopropyl)boronic acid and potassium or cesium carbonate, yielding 3-spiropyrrolidines 52a–c in high overall yields as 1:1 mixture of diastereomers

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• ]. This reaction comprises four main steps: (i) iodide-mediated aryl transfer from boronic acid to selenium dioxide, (ii) reduction of arylseleninic acid to diaryl diselenide, (iii) oxidation of diaryl diselenide to aryl selenenyl iodide with iodine, and (iv) electrophilic substitution of aniline

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• low yield of the first approach. Replacing the catalyst and increasing the temperature or the amount of boronic acid proved to be unsuccessful. With entry 6 (Table 1) it was shown that similar yields could be obtained by removing the ligand and using higher amounts of catalyst. Therefore, no

• synthesis of 5a–t. A mixture of 3a (303 µmol; 109 mg), Pd(PPh3)4 (10 mol %; 369 µmol; 5 mg), NaOH (3.0 equiv; 933 µmol; 37 mg) and the corresponding boronic acid (4-tolylboronic acid, 1.2 equiv; 369 µmol; 5 mg) was dissolved in a mixture of 1,4-dioxane and water 5:1. The reaction mixture was heated to 100

• . Synthesis of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 5a–t. Reaction conditions: 3 (1 equiv), boronic acid (1.2 equiv), Pd(PPh3)4 (5 mol %), NaOH (3 equiv), dioxane/water 5:1, 100 °C, 1 h. aYields of isolated products. Optimization of the reaction conditions for the synthesis of 5a. Photophysical data

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• obtain the 1,3-cuneane selectively. The hydroxymethyl group (185a, 185b, 185f), a boronic acid pinacol ester (185c), a phthalimide-protected aminomethyl group (185d) and an oxazole (185e) were, among others, successful as electron-donating groups yielding 1,3-cuneanes. Iwabuchi and co-workers also found

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• acid, trifluoroborate moiety, trifluoromethanesulfonate, aryl sulfonamides, and heterocycles, have been incorporated into the ortho-position of diaryliodonium structures [16][17][18][19][20][21]. Ortho-trimethylsilyl or boronic acid-substituted diaryliodonium salts can serve as aryne precursors. Ortho

• , expanding the benzocoumarin family (Scheme 1b) [14]. Recently, ortho-functionalized diaryliodonium salts, due to their coordinating and electrophilic effects, have exhibited unique reactivity and chemoselectivity [15]. As such, a wide range of functional groups including the trimethylsilyl group, boronic

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• adjacent or between the two fluorine atoms in these arenes. The synthesis of these two fluoranthene derivatives by Suzuki coupling followed by intramolecular C–H activation was therefore investigated. From (3,4-difluorophenyl)boronic acid and (3,5-difluorophenyl)boronic acid, target products 25 and 26 were

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• coupling: o-Phenylenediamine (1a, 0.05 g, 1 equiv, 0.46 mmol) was added to a round-bottomed flask and dissolved in dry dioxane (5 mL). Next, 2-bromophenyl)boronic acid (7, 0.092 g, 1 equiv,0.46 mmol) was added, followed by the addition of Et3N (0.07 mL, 0.055 mmol), CuI (0.018 g, 0.092 mmol, 20 mol %), and

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• % yields. para-Amino- and boronic acid-substituted benzamides did not react. While meta-bromo-substituted benzamide gave 2j in 84% yield, ortho-bromination resulted in a diminished yield of 2k (55%). We obtained 3,5-disubstituted N-acyl carbazoles 2l and 2m in 91% and 88% yields. The same disubstitution

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• , 63.81; H, 3.74; N, 2.96. Synthesis of 1,2,3-trisubstituted indole 8b (typical procedure) 3-Iodoindole 5a (167 mg, 0.50 mmol), (p-tolyl)boronic acid (7b, 204 mg, 1.50 mmol), Pd(PPh3)4 (28.9 mg, 25.0 μmol), and cesium carbonate (652 mg, 2.00 mmol) were placed in an oven-dried Schlenk tube with magnetic

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• ]azepine and tetrabromothiophene-S,S-dioxide, followed by oxidative aromatization in the presence DDQ to afford compound 25 in an overall 75% yield. Suzuki−Miyaura cross-coupling reaction of compound 25 with (4-ethylphenyl)boronic acid in the presence of Pd(CH3CN)2Cl2, SPhos, and K3PO4 then furnished the