Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• cycloaddition, tandem annulation, intramolecular cyclization, and cross-coupling reactions are commonly employed under thermal conditions, utilizing metal catalysts based on Pd, Ru, Au, Cu, and Fe to access a wide array of substituted quinoline frameworks [29][30][31][32][33][34][35][36][37][38]. Conversely, in

• or epoxystyrene as coupling partners to yield substituted aryl quinolines [54]. However, the methods discussed in the literature often have limitations, such as reliance on stoichiometric amounts of reagents, expensive metal triflates, poor atom economy, and long reaction times. Moreover, many

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• )-2-amino-1,2-diphenylethyl]sulfonamides 2 in 61–74% yields. The sulfonamides 2 were then further reacted with (1S,2S)-cyclohexane-1,2-dicarboxylic acid (3) in the presence of EDCI (3-ethyl-1-(3-dimethylaminopropyl)carbodiimide hydrochloride) as a coupling reagent under the catalysis of DMAP (4

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• Biotin-SAC4A by modifying SAC4A with biotin. (Figure 16) [124]. Monocarboxylated azocalixarene and aminated biotin were synthesized. Subsequently, using a coupling agent, the carboxyl group of the azocalixarene was modified through amidation to obtain biotin-modified SAC4A. The formation of amide bonds

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• . 20% (4 steps) relative to an overall yield of ca. 5% via the preparation of the isonitrile followed by the Fe hydride initiated isonitrile–olefin intramolecular coupling reaction [18]. Protection of the indole nitrogens with the Boc group was preferable to the use of benzyl protecting groups since

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ]. For the synthesis of macrocycles M2 with two BINOL units, we relied on the monoiodide 12, which was first reacted in a two-fold Suzuki coupling to install the first linker, followed by silyl deprotection and introduction of the second linker via nucleophilic substitution [51]. Both procedures require

• synthetic approaches (see Figure 1e) toward BINOL macrocycles had successfully used either Williamson-type reactions or Suzuki couplings for the synthesis of intermediates. Thus, we chose to compare the use of two-fold Suzuki coupling or two-fold Williamson reaction for the synthesis of macrocycles M1. For

• the approach via Suzuki coupling, we employed the previously reported BINOL-diiodide 1 [52], which was reacted with bisboronic acids (see Figure 3a). Here we chose bisboronic esters 75/6/7/8 which feature dimethylphenyl groups that are linked via penta/hexa/hepta/octaethylene glycol chains (throughout

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• (Scheme 7). A combination of the partially armed donor 74 with a disarmed acceptor 75 resulted in an inseparable mixture containing the β,α-linked disaccharide 76, along with multiple by-products. In contrast, coupling of the disarmed donor–acceptor pair 77 and 75 afforded the desired β,α-1,1-disaccharide

• -1,1'-diglucosamine 96 in an excellent yield [95]. Likewise, the coupling of donor 84 with 3-O-Fmoc-protected lactol acceptor 97 gave the orthogonally protected β,α-1,1'-disaccharide 98 as a single product (Scheme 8). It is notable that the 3-O-Fmoc group in lactol acceptor 97 (α/β = 6.5:1) had limited

• favor β-anomer formation, while those with higher RRVs (armed) typically promote the formation of α-anomers [112]. Thus, the 4,6-O-benzylidene acetal group was introduced to produce torsionally disarmed donors 84 and 90 having apparently lower relative reactivity values. Coupling of the 2-N-Troc

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• 1H-13C HSQC NMR analysis was performed to further characterize the structure of 14 (see Supporting Information File 1). 1H NMR coupling constants revealed the presence of one α-glycosidic bond at C1′ (δ 5.49, J = 4.3 Hz) and two β-glycosidic bonds at C1 (δ 4.22, bs) and C1′′ (δ 5.56, J = 3.8 Hz). The

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• cycloamidation of N-alkyl-2-isocyanobenzamides 5 with 2,6-disubstituted aryl iodides 6 (Scheme 2a) [28]. Through a coupling–cyclization reaction sequence, axially chiral 2-arylquinazolinones 7 were synthesized in 35–93% yield with 71–95% ee. Interestingly, by using N-(2,4-dimethoxyphenyl)-2-isocyanobenzamide (8

• high enantioselectivities. Beyond planar and axial chirality, the same group developed a three-component coupling reaction of 2,2′-diisocyano-1,1′-biphenyls 16, aryl iodides, and carboxylates (Scheme 3a) [30]. Under chiral palladium catalysis, unique inherently chiral saddle-shaped bridged biaryls 17

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• the 6/5/5 skeleton, and a Heck coupling reaction constructing the [3.2.1] framework, are the two key reactions in this 11-step synthesis. Keywords: [3 + 2 + 1] cycloaddition; selective estrogen receptor modulators; synthesis; tetrahydrofluorenone; Introduction Estrogen receptors (ERs) [1][2] are

• alkyne moiety is installed via Sonogashira coupling reaction using aryl iodide 5. The cyclopropyl ring in 5 can be introduced via an SN2 reaction of compound 2 with tert-butyl cyclopropanecarboxylate (3). Scheme 5 summarizes the final successful execution of this route. The starting material 2 is a known

• % yield with a cyclopropyl group. Then reducing the carboxylate group in 4 with DIBAL-H afforded alcohol 5 in 67% yield. Next, Sonogashira coupling reaction between 5 and trimethylsilylacetylene generated 6 with an alkyne moiety quantitatively. After that, the hydroxy group in 6 was oxidized into a

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• -crown-6, namely the 1,4,7,10,13-pentaoxa-16-azacyclooctadecane moiety. We next investigated the coupling between the two components of the sensor gathered in Figure 2 at the free and Ba2+-bound states, namely the aza-crown ether-Ba2+-para-phenylene and the benzo[a]imidazo[5,1,2-cd]indolizine components

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• –Hagihara cross-coupling [37][38] of (Sp)-1 with diiodotolane 2 afforded the corresponding ribbon-shaped compound (Sp)-3 in 39% isolated yield. Triisopropylsilyl (TIPS) groups in (Sp)-3 were removed using Bu4NF to afford diyne (Sp)-4 as a monomer in 45% isolated yield. The reaction of (Sp)-4 with

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• in mannosyl PVB 8 (1.0 equiv) in the presence of TMSOTf as catalyst proceeded smoothly at 0 °C to room temperature, affording the α-Man-(1→3)-Man PVB disaccharide. The further coupling of the above PVB disaccharide with the poorly reactive 2-OH in mannoside 9 (0.9 equiv) under activation with NIS and

• motif from PI-88. Finally, the synthesis of the monophosphorylated hexasaccharide 4 was studied (Scheme 4). Orthogonal one-pot coupling of Man PTFAI 5 (1.1 equiv), Man ABz 7 (1.0 equiv), PVB 8 (0.9 equiv), and α-Man-(1→3)-α-Man-(1→2)-α-Man trisaccharide 16 (0.8 equiv) proceeded uneventfully

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• -catalyzed cross-coupling reactions between bromo-substituted perylene or phenothiazine precursors and appropriate donor or linker units, followed by purification via column chromatography and gel permeation chromatography (Figures S18–S21 in Supporting Information File 1). The details of the syntheses are

• coupling in the ground state, consistent with the π-orthogonal molecular design. The introduction of electron-donating TPA groups raises the HOMO energy levels, while the LUMO levels remain relatively unaffected, thereby reducing the HOMO–LUMO gaps. The presence of phenyl spacers in Pe–Ph–PTZ(TPA)2 lowers

• absorption tails were ascribed to the CT transitions between the PTZ to Pe moieties. Pe–Ph–PTZ(TPA)2 exhibited a less pronounced tailing, likely due to the increased spatial separation between the donor and the acceptor by a phenyl spacer, reducing electronic coupling. TD-DFT calculations indicated that, in

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• in detail. Keywords: cyclophane; fluorescence; heterohelicene; intramolecular oxidative coupling; Introduction Conjugated macrocyclic polyarenes have attracted significant attention due to their stimuli-responsive optoelectronic properties, dynamic structural changes, and host–guest interactions [1

• largest macrocycle ever synthesized is a dodecameric hybrid array of 1,2-phenylene, 2,5-thienylene, and 2,5-pyrrolylene units [22][23]. The intramolecular oxidative coupling of these arrays afforded heterohelicene-incorporated macrocycles D and E, depending on the relative arrangements of the pyrrole and

• hybrid decamer 3 in a previous report [26], via a Suzuki–Miyaura cross-coupling reaction between dibromo precursor 1 and borylated precursor 2 (Scheme 1). The resulting mixture was successfully separated by column chromatography on silica using CH2Cl2/n-hexane as an eluent to give icosamer 4 in 6% yield

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• important transformation exhibiting higher chemical and environmental safety. Keywords: alternative solvent; click chemistry; cycloaddition; CyreneTM; 1,2,3-triazoles; Introduction In the past few decades, transition-metal-catalyzed coupling and addition reactions have represented one of the most powerful

• , a wide range of organic reactions, e.g., urea and amide formation [32][33], amide coupling [34], aldol condensation [35], C–H difluoromethylation [36], aromatic substitution [37], and MOFs synthesis [38] were demonstrated in CyreneTM. Very recently, Fasano and Citarella first reported a CuAAC

• results reported by Citarella et al. [39], excellent functional group tolerance was verified and the isolated yields are in the same range as reported by Citarella et al. (for 3a, 90% [39] and 87% [39]). It should be noted that no Cu-catalyzed Glaser-coupling of acetylenes [45] was observed, indicating

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• molecules on graphite [38][39][43] and ultra-thin insulating surfaces [44] is known due to the weak electronic coupling between the molecule and the graphite/insulator surface. We propose that when a sample voltage is applied to the FNAAP adlayer on graphite, they are instantaneously negatively/positively

• electronic coupling between molecules and the metal. We are unable to predict the exact number of charges in the molecule while switching, but what we could demonstrate is that charging can lead to a reduction in the HOMO–LUMO gap, as observed in the experiment. Thus, we propose that the reduction in the

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• ][23][24][25][26]. Most of these synthetic approaches rely on similar strategies, i.e., coupling of the A ring and the C ring followed by the formation of the B ring. Additionally, the semisynthesis of analogues of 1 has been reported and led to the discovery of ISIR-050 (4), which shows higher

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , decarboxylative functionalizations, and Chan–Lam coupling reactions. In doing so, the authors point out the combination of transition-metal catalysis and electrochemistry as an efficient, sustainable method for the oftentimes challenging formation of C–C and C–heteroatom bonds in complex molecules. Another Review

• cross-coupling reactions of bifunctional boryl- and germyl-containing compounds. On the other hand, a Full Research Paper presented by Lee and co-workers introduces a highly regioselective formal hydrocyanation method of allenes [7]. The strategy is based on a copper-catalyzed hydroalumination of

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• , and the huge overall economic impact of these processes. Inspired by the logic behind cross-dehydrogenative C–C-coupling methods [15], the direct C–H amination has been developed as a more straightforward, economical and environmentally friendly reaction, compared to its counterparts (such as the

• ][44] and sulfamoyl chlorides [32] can perform the coupling under basic conditions, the need for the activation of the amine as an electrophilic agent generates additional waste. This reduces atom economy and indicates lower reaction efficiency. Acid-catalysed protocols have also been specifically

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• in THF at 65 °C, which are typical conditions for the McMurry coupling (Scheme 2) [24][25]. This reaction afforded an internally functionalized DBC derivative 6 in 60% yield, which adopts an unsymmetric structure with methyl and hydroxy groups on the central carbon atoms. The structure of compound 6

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• [5]helicene (compound 57b) by coupling two 12H-benzo[b]phenoxazine (BPO) units and systematically compared it to its N,N-analogue (compound 57a) derived from 13H-dibenzo[b,i]phenoxazine (DBPO) scaffolds [72] (Table 19). Compound 57b was obtained in significantly higher yield and, like compound 57a

• double aza-oxa[7]helicene via oxidative coupling followed by dehydrative cyclization [85]. The resulting meso-isomer (P,M)-71 emerged as the major product, exhibiting dual emission bands at 415 and 440 nm and solvent-independent absorption at 407 nm. Expanding the structural diversity, the group

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• 5 mm tubes. The corresponding operating frequencies were 500.13 MHz and 125.77 MHz, respectively. The chemical shifts are quoted in parts per million (ppm) with an accuracy of 0.01 ppm. The coupling constants (J) are described in Hz and determined with an accuracy of 0.1 Hz. To describe the spin

• )quinolin-7-ol (2) Diazotization of pentafluoroaniline has been recommended to be carried out in nonaqueous media or concentrated mineral acid, otherwise the coupling product always contains a hydroxy group on the perfluorophenyl ring at the position para to the azo group. It appears that when solutions of

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• signal at δH 8.97 (s, H-18), δH 7.41 (s, H-20) and a quaternary carbon (C-16) assigned at δC 131.4 that reminiscences a histamine subunit absent in compound 1. This observation was supported by the 1H-1H COSY spectrum that displayed a cross-peak coupling of H2-14 to both carboxamide protons H-13 and H2

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• ) [48]. Good yields were obtained only when CuI was used in combination with 1,10-phenanthroline as a ligand, and this intramolecular Ullmann-type coupling was found to be compatible with primary, secondary and tertiary alcohols, with secondary alcohols exhibiting the following order of reactivity

• transformation of alkenylstannanes into acetylated acyloins, Fürstner et al. [49] reported the synthesis of two 2-alkylideneoxetanes 57 via an unexpected Cu-catalysed intramolecular cross-coupling of hydroxyvinylstannanes 56 (Scheme 15). Besides the good yields, the stannane substrates were also readily prepared

• by trans-hydrostannation [50] of the corresponding alkyne precursors, so this report potentially introduced a new method for oxetane synthesis through an intramolecular Chan–Lam-type coupling. Due to the high reactivity of the exocyclic enol ether induced by the ring strain, 2-alkylidene

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• cross-coupling reactions, such as the Suzuki sp2–sp2 coupling or Sonogashira sp2–sp coupling. These reactions enable the modular construction of complex precursors, which can then be transformed into azulene-embedded PAHs in the final step. Two main synthetic strategies are commonly employed: 1) The

• , the synthesis of more complex molecules may require elements of both strategies. Construction of the azulene moiety in the final step Oxidation of partially saturated precursors: With modern cross-coupling reactions providing access to larger precursors, a synthetic strategy involving the

• exceptionally high yield (97%). A Suzuki cross-coupling reaction between 47 and 45 gave compound 48 which was subjected to a final Scholl oxidation using DDQ. The target compound 49, containing two azulene subunits, was obtained in a relatively low yield (16%). Analysis of NICS values for 49 revealed similar