Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• in steering catalytic selectivity. In 2016, the Jiang group achieved regioselective control in the gold-catalyzed intramolecular hydroarylation of alkynes by modulating the electronic and steric effects of ligands (Scheme 2) [20]. Mechanistically, the electron-deficient phosphite ligand L1 and the

• undergoes intramolecular cyclization into a proximal C(sp2)–H bond (ΔG‡ = +19.7 kcal·mol−1) to form Int-46, which reacts with 4-MePhSH (ΔG‡ = +14.9 kcal·mol−1) to yield radical intermediate Int-47 and a thiyl radical (4-MePhS·). Sequential thiol-assisted hydrogen shifts produce Int-48, followed by

• -methylacryloylbenzamides, and 2-iodobiphenyls – thereby selectively synthesizing silacyclic compounds with varying ring sizes, including ten-membered, seven-membered, and five-membered rings. Mechanism (Scheme 15): Substrate 53 undergoes oxidative addition with Pd(0), followed by intramolecular carbopalladation to form

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• . Finally, the new enolate E evolves through intramolecular proton abstraction and elimination of boryllithium [20][21]. The formation of side product 3 observed when dichloromethane was used as a solvent could be explained by protonation of intermediate A, followed by transmetalation of the resulting

• mechanism for the Cu-catalyzed dimerization of 4,4-dichoro-2-butenoic acid derivatives. a) KOt-Bu-mediated intramolecular cyclization of 9. b) Direct formation of cyclopropane 20 from gem-dichloride 5 using KOt-Bu as base. Optimization studies. Synthesis of densely functionalized (2,2-dichlorovinyl

• )cyclopropanes by base-promoted intramolecular cyclization. Supporting Information Supporting Information File 2: Experimental procedures, characterization data and copies of NMR spectra. Funding Financial support from the AEI (PID2020-118237RB-I00), European Research Council (863914), Xunta de Galicia (ED431C

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• , and control reactions support sensitization, enabling an intramolecular [2 + 2] cycloaddition to be realized accessing 3D bicyclic fragments containing a boron handle. Keywords: boron; catalysis; [2 + 2] cycloaddition; energy transfer; photochemistry; Introduction The strategic use of a photon to

• . Herein, we demonstrate the sensitization of alkenylboronates to enable efficient intramolecular [2 + 2] cycloaddition using high energy photosensitizers (Figure 1C). Sensitization was quickly established and explored through the use of alkene scrambling (geometrical isomerization) reaction probes, to

• generated triplet diradical in an intramolecular system. To further assess the properties relevant for intramolecular reactivity, substrate 3b was designed (see Supporting Information File 1 for full details), given that non-activated α,β-unsaturated systems are also comparatively underexplored via EnT

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• forms 3a’–e’ will be attacked by methylamine (4) to yield the tetrahedral intermediate 6 and then, the intramolecular proton transfer will lead to intermediate 7. It has been proven that Schiff’ bases show normally higher reactivity than the corresponding carbonyl compounds towards nitrogen-containing

• a dihedral angle of 49.86(10) 86.22(11)° with the phenyl rings C6–C11 and C18–C23, respectively. The angle between both phenyl rings is 70.76(11)°. The stereochemistry around the double bond is Z, allowing an intramolecular N–H···O hydrogen bond between one of the carbonyl oxygen atoms and the amino

• ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown as red dashed line. The bioavailability radar of studied compounds 5a–e. The interactions of potential drugs 5a–c in the active site of enzyme iNOS. The interactions of potential drugs 5d and 5e and control drug (DEX) in the

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

• phenyl rings' ortho, meta, or para positions. This method proceeded via an anodic oxidation, followed by intramolecular cyclization (Scheme 32). The key role of anodic oxidation became evident when the annulation product

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• internal rotation in 11 via TS8 and reaction with TMSCN to give adduct 13 (see Figure 3). Distances and bond lengths are given in pm. Catalyst 7 is replaced in TS 11-12 by concerted electrophilic intramolecular substitution with formal trimethylsilyl cation as electrophile. Please note the surprisingly

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• was impractical for the HBC derivative with a C4-handle (N-(4-bromobutyl)-HBC) due to intramolecular cyclization with the amine. To prevent intramolecular cyclization, we considered the 4-bromobutyl HBC ether 11 as a potential candidate with a 4-atom spacer. Accordingly, 4-hydroxybenzaldehyde was

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• a potentially valuable tool for molecular design. Additional stabilisation of the gauche conformation of vicinal fluorohydrins can also be afforded by an intramolecular H-bond (II, Figure 8) [96][97][98]. Fluorine is a weaker H-bond acceptor than oxygen or nitrogen [99][100][101], but F···H

• attraction can still be significant in some contexts [102][103] and the intramolecular H-bond depicted in II (Figure 8) can have a significant impact upon the properties of vicinal fluorohydrins [97]. The possibility of intramolecular H-bonding in vicinal fluorohydrins has important consequences for the

• molecules’ intermolecular interactions too. The intramolecular H-bond makes the hydroxy group a weaker intermolecular H-bond donor [104] (e.g., 55 vs 54, Figure 8). This runs counter to a longstanding assumption [105] that the inductive effect of fluorine should always make the hydroxy group a stronger H

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• 10.3762/bjoc.21.50 Abstract The electrochemical synthesis of 2-aminoprolines based on anodic decarboxylation–intramolecular amidation of readily available N-acetylamino malonic acid monoesters is reported. The decarboxylative amidation under Hofer–Moest reaction conditions proceeds in an undivided cell

• [7][8] (Figure 2, reactions 1 and 2, respectively). Results and Discussion N-Acetylamino malonic acid monoester 9a possessing a tosyl-protected tethered amine was selected as a model substrate for the development of the intramolecular amidation under Hofer–Moest conditions. The acid 9a was prepared

• initial deprotonation of carboxylic acid 9a by cathodically generated hydroxide is followed by anodic oxidation/decarboxylation of the formed carboxylate 9a-I to generate stabilized cation 9a-II. The latter undergoes intramolecular cyclization with the tethered N-nucleophile into cyclic aminal 6a. In a

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• simonsol C, two reports have utilized alkaline dearomatization strategies and another report used an intramolecular Heck reaction as the key reaction [5][6][7]. However, there have been no reports or studies utilizing acidic dearomatization, which is also effective, to synthesize an arylated quaternary

• carbon center. In the first report on the total synthesis of simonsol C (Scheme 1), in 2016 Banwell’s group employed an intramolecular Heck reaction as key step to furnish the aryl-containing quaternary center and simultaneously construct the benzofuran skeleton [7]. This synthesis involved a total of 12

• scaffold of simonsol C, utilizing an alkaline dearomatization as the key reaction, followed by a functional-group-selective Wittig reaction and concurrent oxy-Michael addition [6]. A bromophenol acetal was used in the intramolecular alkylative dearomatization, which was first reported by Magnus et al. [8

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

• peptide carbonyl group. Both moieties result from the glyoxylate compound (Scheme 43). There are many examples in which the ester moiety opens the possibility of a further intramolecular cyclization with a nucleophile (for example, a protected amine in an Ugi/deprotection/cyclization sequence [98][99][100

• proton in the C-α position, which leads to a stable carbanion with even mild bases, that can promote intramolecular cyclization. For example, Flores-Constante et al. [106] and Nechaev et al. [107] synthesized Ugi adducts with a propargyl group that could be used as a Michael acceptor (48–50, Scheme 44

• salts and TEMPO as the radical initiator/oxidant couple that promoted the intramolecular radical cyclization of suitable 1,3-dicarbonyl Ugi adducts 54 and 55 (Scheme 45) [108][109]. The stabilization of the enol in the 1,3-dicarbonyl Ugi adduct allows single-electron transfer (SET) with the anion

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• intramolecular hydrogen bond between the NH-unit and the carbonyl group. The presented results indicate that the reaction of the aliphatic amine doesn’t lead to recyclization of the studied heterocyclic system. Further, we hypothesized that synthesis of the enamine 4a can be realized in one-pot variant without

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• bimanes studied: a) Cl2B (B), representing 90% of the disordered asymmetric unit, b) Me2B, not disordered with dotted line representing an intramolecular hydrogen bond, and c) Me4B showing the majority occupied (55%) N–N moiety. View of the molecular structure in the crystal of a) symmetry generated by

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• were required to obtain the corresponding mesylate 3b. Similar to 11, compound 12 was isolated as its trifluoroacetate salt. Selective Boc protection of the aliphatic amine gave 13, which was selectively O-mesylated to give compound 14. Compound 14 was found to slowly undergo intramolecular cyclization

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• approach would conceptually differ from previously reported anodic syntheses of cyclic diaryl iodonium compounds, where an electrochemically generated acyclic iodine(III) intermediate undergoes an intramolecular SEAr-type reaction to form the cyclic product [19][20]. Herein, we report on the development of

• Br(II) followed by subsequent deprotonation to generate radical B. A following disproportionation of radical B would lead to the formation of Br(III) species C (anodic oxidation cannot be fully excluded), which undergoes intramolecular SNAr-type substitution to form cyclic λ3-bromane 1a and

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• reaction and Diels–Alder [4 + 2] cycloaddition based on vinylfuran and 1,3-butadienylfuran derivatives was designed and studied. It was found that in the case of 3-(furan-2-yl)acrylaldehyde, a one-pot Ugi reaction and intramolecular Diels–Alder vinylarene (IMDAV) reaction leads to the formation of the

• yields. The studied tandem Ugi and intramolecular Diels–Alder reactions allow high substituent variation in the named isoindoles. Keywords: 1,3-butadienylfuran; furo[2,3-f]isoindole; intramolecular Diels–Alder reaction; isoindole; one-pot; Ugi reaction; vinylfuran; Introduction Energy-saving and

• construction [27][28]. For instance, the intramolecular Diels–Alder reactions of vinylarenes (IMDAV) strategy [29][30] has been used to synthesize annulated isoindoles, including thieno[2,3-f]isoindoles [31][32] and furo[2,3-f]isoindoles [33][34], from thienyl- or furylallylamines and unsaturated acid

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• , Scheme 18) gave product 108 with higher 1,2-cis selectivity. In protocol A, the tosylamide forms an intramolecular hydrogen bonding with the benzylic oxygen forming a quasi-bicyclic intermediate acting as a 1,2-trans directing protecting group. Thus, following subsequent formation of the oxocarbenium ion

• disturbs the intramolecular hydrogen bonding, as in 107 thereby generating a non-participating form as an intermediate. Thus, the acceptor easily attacks from the α-face of the sugar ring, and thereby, leading to the product with higher 1,2-cis stereoselectivity (87:13). A similar bimodal protocol was also

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• reactions of 2-methylquinolines with 3,5-di-(tert-butyl)-1,2-benzoquinone [1] and benzophenones with o-chloranil [15]. The norcaradiene derivatives 5, formed in the next step by the intramolecular cyclization reaction of 4, undergo thermal isomerization into 2,3-dihydrotropolones 6. The formation of 2

• increase in the intramolecular hydrogen bond length NH···O of the (NH) isomers and a decrease in the magnitude of hydrogen bond N···HO of the (OH) forms (Figure 1). On the other hand, the position of the benzoannelated fragment does not significantly affect the structural and energetic parameters of the

• the previously obtained 2-(indolin-2-yl)-1,3-tropolone)). The angle between the planes C(2)C(3)C(6)C(7) and (3)C(4)C(5)C(6) is equal to 27.6° (34°). In compound 7b, as in 2-(indolin-2-yl)-1,3-tropolone, an intramolecular hydrogen bond N(1)–H(1)···O(2) was realized with parameters: distances N–H = 0.86

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

• formed. This reaction only occurs close to the photocatalyst or sensitizer fixed at the intracellular target, for example at tubulin. An intramolecular Diels–Alder reaction followed by nitrogen extrusion

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• (13%). BPP-dione, when compared to the parent BPP, also displayed improved absorption and emission from the first excited singlet (S1) state with a PLQY of 62% and an intramolecular charge-transfer character. The rod-like nano- to microcrystals as well as longer wires of these BPPs were also revealed

• by scanning electron microscopy. The intriguing optical properties of BPP and its derivatives may lead to their application as fluorophores. Keywords: benzo[rst]pentaphene; intramolecular charge transfer; nanocrystals; photoluminescence; polycyclic aromatic hydrocarbon; Introduction Polycyclic

• , in comparison with parent BPP 2. Notably, both BPP-OiPr 3 and BPP-dione 4 displayed enhanced PLQYs while a significant solvent-polarity dependence of the emission was observed only for the latter, suggesting the photoinduced intramolecular charge-transfer character of 4. Moreover, BPPs 2–4 formed

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• abstraction to yield the hydrodifluoromethylation product. Building upon this work, we hypothesized that if the newly formed alkyl radical could undergo intramolecular cyclization with an aromatic ring, instead of hydrogen abstraction, it could enable the construction of polycyclic structures. Thus, as part

• intermediate D via intramolecular radical cyclization. A single-electron-transfer (SET) process then occurred between the radical B and the radical D, resulting in the generation of cationic intermediate E, difluoroacetate anion and PhI. Finally, the product 3a was obtained after the deprotonation by

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

• coupling of alkyne 8, THIQ segment 9, and benzaldehyde would enable convergent assembly of the building blocks to produce 10 [43][44][45][46]. Removal of the cyclic acetal in 10 followed by Strecker-type conversion leading to an α-amino nitrile would enable tandem intramolecular cyclization with phenol to

• form 2,3-diaminobenzofuran 11. The subsequent gold(I)-mediated intramolecular 6-endo hydroamination of 11 would construct the left THIQ ring to furnish the substructure 14 of saframycin A (1) [47][48][49][50][51]. To selectively promote the desired 6-endo cyclization (11 → 12) over the competing 5-exo

• transformations: copper(I)-catalyzed regiocontrolled three-component assembly of alkyne 8, THIQ segment 9, and benzaldehyde to yield 10, followed by tandem Strecker reaction and intramolecular cyclization to form 2,3-diaminobenzofuran 11. Subsequent gold(I)-mediated 6-endo hydroamination of 11 leads to the

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• the desired thienopyrimidones 5a–e, quinolinopyrimidones 6a–e and indolopyrimidones 7a–e, respectively, as reported in the literature [42][44]. In accordance with the reported mechanism, after the initial formylation of the amino group at position 2, an intramolecular nucleophilic attack by the NH

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

• enantioselectivity. Furthermore, a lactam containing a quaternary carbon center (2g) was prepared. However, a lower enantioselectivity was observed for product 2h due to the similar steric environment of the two alkyl substituents. As shown in Figure 1, a catalytic cycle was proposed for the intramolecular C–H

• ) nitrenoid intermediate INT-7. Subsequent nitrene insertion, protodemetalation, and intramolecular cyclization furnish the desired 1,2,4-triazole. 1.3 Three-component formation of N-acyl amidines In 2019, N-acyl amidines were prepared from dioxazolones using a copper catalyst with terminal alkynes and

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

• aromatic amide macrocycles [36][37][38][39][40][41][42], a class of cyclic compounds comprising a number of aromatic residues with consecutive intramolecular hydrogen bonds and amide linkages, stand out as versatile host molecules as their cavity size, peripheral side chains, and recognition sites are