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

• -disubstituted and 4-substituted quinoline molecules. The developed strategy involves an earth-abundant Fe-catalyzed C(sp2)–C(sp2) bond cleavage of styrene, followed by the hydroamination of the cleaved synthons with arylamines and subsequent C–H annulation to yield two valuable quinoline derivatives. Key

• strategies have been explored in recent decades for the synthesis of structurally diverse quinolines. Among them, transition-metal-catalyzed multicomponent reactions (MCRs) have emerged as particularly effective for constructing complex quinoline-based heterocycles [26][27][28]. Catalytic pathways such as

• [53]. In this work, the authors used a stoichiometric amount of Zn(OTf)3 as a Lewis acid catalyst and air as the oxidant for the reaction. Jana and colleagues demonstrated an atom-efficient pseudo-three-component C–H annulation reaction catalyzed by Yb and Cu, which involved nitrosoarenes and styrene

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

• bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines

• bisoxazolines [1][2][3][4][5][6][7][8][9] and bisimidazolines [10][11][12][13][14][15] are efficient chiral ligands and have been widely applied in various metal-catalyzed asymmetric organic transformations. Various chiral bisoxazoline ligands have been prepared from diacids and enantiopure vicinal amino

• alcohols and utilized in different metal-catalyzed asymmetric organic reactions [1][2][3][4][5][6][7][8][9]. In comparison with bisoxazoline ligands, relatively less attention has been paid to bisimidazoline ligands [10][11][12][13][14][15]. Some well investigated bisimidazoline ligands are pyridine-linked

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

• Cu-catalyzed click chemistry to construct a photo-responsive macroscopic switch. This switch can achieve photo-controlled chiral reversible recognition of (1R,2S)-1-amino-2-indanol through changes in contact angle, and it holds promise for applications in chiral drug controlled release and other

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• electrolysis conditions and its removal was compatible with the double bond and acetal functions in ester 3d (see Supporting Information File 1 for attempts of other protecting groups such as Boc, Troc, and tfa). However, Pd-catalyzed N-Alloc deprotection induced isomerization of the double bond leading to the

• of products in copper-catalyzed 1,4-addition of phenylmagnesium bromide, Giese reaction with 2-iodopropane, Simmons‒Smith or Johnson–Corey–Chaykovsky cyclopropanation, hydroboration reaction with 9-BBN, and Diels–Alders reaction with Danishevsky diene. Gratifyingly, it was found that vinyloxazoline S

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

• ]. Unfortunately, testing of malassezione is limited by the lack of a convenient synthesis. Indeed, beyond isolating the compound from cultured M. furfur [11][20], the only reported synthetic route to malassezione is via an iron-catalyzed Fukuyama-type indole synthesis, which afforded the compound in low yield [18

• subsequent iron-catalyzed reaction afforded 1 in only 35% yield. To avoid the low-yielding preparation of the isonitrile, we elected to use commercially available indole-3-acetic acid as the starting material, and to utilize an approach similar to that described for the synthesis of dibenzylketones from the

• debenzylated by Pd-catalyzed hydogenation to cleanly yield 25c. This affords a route to such compounds bearing hydroxylated aromatic groups that employs milder conditions than previously reported [22][24]. Finally, we prepared N,N′-dibenzylmalassezione (25d). Initially, this compound was prepared with the

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

• . tuberculosis [121]. The TMS-glycosides were prepared from the corresponding hemiacetals by acid-catalyzed silylation, involving a silica gel-promoted in situ anomerization of the O-TMS-β-glycoside to its more thermodynamically stable α-counterpart [121]. This protocol enabled the efficient synthesis of TMS

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• latent failure modes (e.g., reactor fouling due to precipitation of polynitro by-products or acid-catalyzed polymer formation) that conventional short-term experiments often overlook but are especially prevalent in continuous nitration systems. This systematic validation approach enables predictive

• analysis revealed an autocatalytic profile at 45 °C characterized by a distinct 50-second induction period preceding measurable conversion [59]. The ionic mechanism, particularly well-established for aromatic substrates, involves the acid-catalyzed generation of nitronium ion (NO2+) through nitric acid

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• Scientific) and readily available in bulk quantities compound. In organic synthesis, it is most commonly used in metal-catalyzed reductions where NaH2PO2 serves as a molecular hydrogen donor [6][7][8][9][10][11][12][13][14][15][16]. However, recent studies demonstrated application of hypophosphites as a

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

• ], insertion reactions [16][17][18], cycloaddition reactions (e.g., [4 + 1], [3 + 2]) [19][20], and others [21][22][23]. Particularly, isocyanides have been widely exploited toward the preparation of centrally chiral structures through transition-metal-catalyzed or organocatalytic asymmetric reactions [24][25

• reaction type and the chirality type of resulting products. Perspective Isocyanide-based transformations Palladium-catalyzed isocyanide insertion reactions In 2018, Luo, Zhu, and co-workers developed a palladium-catalyzed enantioselective reaction between ferrocene-derived vinyl isocyanides 1 and aryl

• ). However, the diastereoselectivity is modest (1.7:1), likely resulting from insufficient chiral induction during the indolinone-forming step. Moving forward, this strategy was applied in the construction of axial chirality by the same group. In 2021, they reported a Pd(OAc)2/L2-catalyzed imidoylative

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• thematic issue that visible light increases the reaction rate of palladium-catalyzed Negishi cross-couplings [34]. The integration of enabling technologies has also contributed to the success of photocatalytic organic synthesis [35]. Automated reaction platforms, high-throughput experimentation techniques

• , and flow chemistry are being harnessed to push the limits of light-driven reactions [36]. Terada and colleagues show in this thematic issue how flow chemistry is used to significantly improve the yield of a π-Lewis acidic metal-catalyzed cyclization–radical addition sequence [37]. Recently, chemists

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

• University, Beijing, 100871, China 10.3762/bjoc.21.127 Abstract A formal synthesis of product VI with tetrahydroflurenone structure as selective estrogen receptor modulator has been realized. The Rh-catalyzed [3 + 2 + 1] reaction of yne-vinylcyclopropanes and CO (20 mmol scale, in 87% yield) for building

• . Applying the traditional solvent dioxane for the [Rh(CO)2Cl]2 catalyzed [3 + 2 + 1] reaction (the catalyst loading was increased from 5 mol % to 10 mol %) gave 9 in only 26% yield. To our delight, the reaction yield could be improved to 87% by using mesitylene [30] as the solvent and the loading of [Rh(CO

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• Cope rearrangements [20]. More recently, Alabugin and co-workers reported that the gold(I)-catalyzed propargyl rearrangement depicted in Scheme 1b also follows a concerted oxonia Claisen pathway (via an aromatic TS) rather than through a higher barrier 6-endo-dig cyclization [21], which provides

• concerted mechanisms has not been considered. For instance, very little is known about the influence of TS-aromaticity (if any) on the barrier heights of catalyzed pericyclic reactions and related transformations. Our group has been focused on this aspect in recent years by exploring the interplay between

• this perspective article, we shall show the relationship between transition-state aromaticity and reactivity in representative pericyclic reactions. Perspective Lewis acid-catalyzed Diels–Alder cycloadditions It is well-established that catalytic amounts of a Lewis acid (LA) can significantly

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• method for the synthesis of 3-arylbenzo[4,5]thieno[3,2-b]pyrroles has been developed via pyrrole ring annulation to the aromatic benzo[b]thiophene system, using 3-arylazirines as a N‒C=C synthon. The reaction is catalyzed by Ni(hfacac)2 and proceeds through the azirine ring opening across the N=C3 bond

• arenes with azirines. These include the [3 + 2] cycloaddition of azirines to arynes (Scheme 1, reaction 1) [10][11][12], Pd-catalyzed reaction of azirines with iodoarenes (Scheme 1, reaction 2) [13], and reaction of 2-aroylazirines with naphthols (Scheme 1, reaction 3) [8]. The [3 + 2] annulation

• heteroaromatic system have been reported to date. The formation of dihydrobenzofuro[3,2-b]pyrrole cycloadducts as by-products has been observed in the synthesis of aziridines by the transition metal-catalyzed reaction of benzofurans with 3-arylazirines [16]. This paper presents the use of azirines as annulation

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

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

• CyreneTM, as a biomass-originated polar aprotic solvent, could be utilized as an alternative reaction medium for one-pot copper(I)-catalyzed azide–alkyne cycloaddition (click or CuAAC) reactions, for the synthesis of various 1,2,3-triazoles under mild conditions. Nineteen products involving N-substituted-4

• 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

• methods, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the so-called click reaction [7], has received substantial attention for the selective synthesis of various 1,2,3-triazoles that are of utmost importance in the synthesis of biologically active compounds such as active

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

• -mediated reaction for the synthesis of enaminones from 3-bromochromones (Scheme 1D). Initially, a Ni(II)-catalyzed hydroamination protocol affords the intermediate 2-amino-3-bromochromanones, which upon photocatalytic dehalogenation and subsequent opening of the heterocyclic ring provide the corresponding

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• . Commercial CaO catalyzed the transesterification with an 81% yield of fatty acid methyl esters (Table 1, entry 2). Ca(OH)2 showed weak transesterification activity and the yield of fatty acid methyl ester mixture was 26% (Table 1, entry 3). Similar results were obtained for the uncalcined carbide slag (CS25

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

• as electron or hole-induced switching. Depending on the polarity of the bias, either an electron is injected (at positive sample bias) or a hole (at negative sample bias). This may be directly compared to the electron or hole-catalyzed isomerization of molecules in solution [40][41][42]. Generally

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

• brassicicene biosynthesis-related gene cluster (BGC) in Alternaria brassicicola and Pseudocercospora fijiensis [34][35]. The 5-8-5 tricyclic scaffold is transformed into various fusicoccane natural products catalyzed by P450s, dioxygenases, dehydrogenases, and reductases. Therefore, we propose to harness the

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

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

• papers (three Full Research Papers and two Letters) contributed by scientists from Asia and Europe. The breadth of topics and the geographical diversity of the authors reflect the global interest in copper catalysis today. The Review article by Yang and Fang focuses on copper-catalyzed yne–allylic

• substitution pattern on the regioselectivity and stereoselectivity of the reactions. A Review article by Papis and co-workers discusses various copper(II) triflate-catalyzed multicomponent reaction types [2]. Therein, the synthesis of cyclic and acyclic compounds, as well as three-component and four-component

• community in that it elegantly reviews recent advances in allylation reactions of copper-catalyzed asymmetric allylic substitution reactions of chiral secondary alkylcopper species [5]. In summary, the contribution includes stereospecific transmetalations of organolithium and -boron compounds, copper

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

• absorption and emission maxima (λabs = 399 nm, λem = 405 nm), a fluorescence quantum yield (ΦF) of 0.13, and high dissymmetry factors (|gabs| = 1.9 × 10−2, |gabs| = 9.5 × 10−3 at 403 nm) [18] (Table 2). Miura and co-workers employed Pd(II)/Ag(I)-catalyzed cyclizations to construct azahelicenes, with compound

• , enantioselective synthetic approach toward azahelicenes via a chiral phosphoric acid-catalyzed multicomponent Povarov reaction or oxidative aromatization [32]. Among the synthesized compounds, compound 19 displayed dual absorption bands at 260 and 325 nm and emission peaks at 420 and 440 nm, which red-shifted to

• stimuli-responsive chiral electrochromic materials. In the same year, You’s group developed a transition-metal-catalyzed C–H/C–H-type regioselective C3-arylation of benzothiophenes using molecular oxygen as the oxidant [79]. This strategy afforded the TADF-active compound 64a, which exhibits efficient

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• Mannich reactions [20], lipase-catalyzed esterification [21], nitro-aldol [22], Michael [23], and aza-Michael reactions [24][25], Diels–Alder reactions [26][27] and Friedel–Crafts alkylation of indoles [28]. Many high pressure reactions were applied in natural product synthesis [29]. The high pressure

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• molecules. On the other hand, C–H bonds exhibit low reactivity due to their relatively high bond dissociation energy (BDE) (Figure 1a). Therefore, the direct functionalization of C–H bonds is extremely challenging [1][2][3][4][5]. In recent decades, transition-metal-catalyzed C–H bond functionalization

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• the photocatalyst [Ir(dF(CF3)ppy)2(4,4'-d(CF3)bpy)]PF6 in combination with a base (NBu4OP(O)(OBu)2) (Scheme 1) [59]. The generation of amidyl radical 5 involved a stepwise PCET process catalyzed by the combined effect, in the presence of photocatalyst and the base. Subsequently, amidyl radical 5

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

• palladium-catalyzed C–H arylation afforded the fused azulene-embedded PAHs 71–74 in good yields (40–70%). All non-alternant isomers of linear acenes exhibit azulene-like lowest energy optical absorption, attributed to the azulene-like S₀→S₁ transition. Condensation reactions: Various condensation reactions

• -fold palladium-catalyzed [5 + 2] annulation was performed using 3,9-diboraperylene [64] 87 and 1,2-dibromoacenaphthylene 88, yielding the azulene-embedded PAH 89 with an isolated yield of 15% (Scheme 13) [65]. While the azulene subunits in 89 were shown to be antiaromatic in the neutral PAH, oxidation

• unexpected deboronization reaction upon the addition of TFA. On-surface synthesis Recently, the field of on-surface chemistry has made significant progress, with the successful development of complex metal-catalyzed on-surface reactions that are not accessible through classical solution-based organic