Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• interactions and enhanced electronic stabilization through lithium coordination. This explains the critical role of lithium in achieving a high enantioselectivity. Isotope-labeling experiments using 10B-enriched 1,1-diborylalkanes (S)-49 further supported this mechanism, showing a stereoinvertive

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

• 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

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• organized polarization rather than “confinement,” specifically positing that oriented electric fields rule transition-state stabilization for many reactions [33][34][35]. These fields stabilize charge redistribution during a reaction, usually at a small locus of each substrate molecule. It follows

• , therefore, that for redistribution penalties to be lessened, the equal and opposite stabilization must be granted to that same space. This is the basis of bifunctional/dual activation, as shown in Figure 1. Since very few reported supramolecular cavity designs provide bifunctional activation, cavity

• catalysis has fared best using approaches such as destabilizing ground states by constrictive binding, guiding molecular collisions to reduce large entropic costs (e.g., pericyclic reactions), and broad, undirected coulombic stabilization of charged transition states [36], for example of cations by

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• also applied to o-carboranes fused with five-membered ring systems [39][40]. The positioning of the heteroatom in these exo rings governs bonding, leading to restricted conjugation and, consequently, no aromatic stabilization. Importantly, the magnetic field generated by the 3D cluster influences the

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

• thermodynamically more stable than the corresponding (OH) forms. Increasing the polarity of the medium additionally enhances their stabilization. The introduction of an additional acceptor substituent to the tropolone moiety has a similar effect. In addition, compared to compounds 7a,b, compounds 8a,b show a marked

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• ] reported a stable heptacene dication in concentrated sulfuric acid, a stability attributed to the intermolecular Coulomb repulsion between the charged molecules, which prevents the dimerization of the acene. This exciting finding suggests possible modes of kinetic stabilization of oxidized species of π

• report that compounds 1 and 2 can both be easily oxidized to form relatively stable radical cations (1•+, 2•+) and dications (12+, 22+). Interestingly, oxidation reverses local antiaromaticity to aromaticity, a transition that is particularly noticeable in 1 → 1•+ → 12+, where stabilization of the

• stabilization of such redox states. Results and Discussion Electrochemistry Figure 2 shows the electrochemical cyclic voltammograms of 1 and 2, in which two reversible oxidation processes can be observed. By considering the half-wave potential values obtained from the cyclic voltammograms, two one-electron

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

• groups in organic synthesis [1][2][3][4]. In chemistry and biology, disulfide bonds play crucial roles in protein folding and stabilization [5][6][7][8] and in the rubber industry, they are used to link different polymer chains [9][10]. The disulfide bond backbone is commonly used as a linker for

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

• enantioselectivity is the introduction of serine-derived bisoxazoline ligands L8 (sBOX). Upon coordination with a copper catalyst, these ligands present second-sphere ester groups, which facilitate the additional stabilization of noncovalent interactions at the penta-coordinated Cu(III) intermediate 82 in the

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• effect of fluorinated rings and the decisive role of arene–fluoroarene interactions in both mesomorphism induction and stabilization. Thus, 2Li-BP was reacted with C6F5–C6F5 to produce 2-perfluorophenyl-1,3,4-trifluorotriphenylene (F), in 37% yield and 2,3,6,7-tetrakishexyloxy-10-phenyltriphenylene (BTP6

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• ; Loschmidt group element; molecular graph; Introduction A classic textbook tetrad linking hydrocarbon acidity to aromatic stabilization energy comprises cyclopentadiene (CpH), indene (InH), fluorene (FlH), and diphenylmethane (DPMH) [1][2], with pKa values in DMSO equal to 18 [3], 20.1 [3], 22.6 [3], and

• 32.2 [4], respectively (Scheme 1) [5][6]. The reaction enthalpy for deprotonation of CpH is ca 20 kcal/mol less endothermic than DPMH and ca. 24–27 kcal/mol less endothermic than 1,4-pentadiene (PDH; pKa ≈ 35 in DMSO) [3], values strikingly similar to the resonance stabilization energy estimated for

• benzene [7][8]. Furthermore, the trend of pKa values for CpH, InH, and FlH correlates with the reduction of the aromatic stabilization energy for the anion across the series [1][2]. At first glance, this model supports the notion that the relative pKa values of cyclopentadienes embedded in polynuclear

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• the deslipping-based conversion process [46]. Moreover, considering the similar activation entropy values, the faster deslipping of [3]rotaxane was mainly caused by its lower activation enthalpy than that of [2]rotaxane owing to the stabilization effect derived from the inclusion structure formation

•  9C) [47]. Regarding the methoxy substituent, no inclusion formation was observed in the [2]rotaxane framework, whereas a shuttling motion of the wheel was observed on the axle moiety, indicating that a different stabilization effect was exerted based on the axle-end structures (Figure 9D). Such a

• stabilization effect could be affected by the bulkiness and polarity of the axle-end moieties. Meanwhile, the deslipping reaction of some [3]rotaxanes directly yielded the dumbbell and two wheels without any [2]rotaxane intermediate, indicating that the deslipping on [2]rotaxane proceeded faster than on [3

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• cyclodextrin host, in contrast to β-CD where their interaction with the inner walls of the CD can be neglected and therefore does not contribute to the stabilization of water complexes. As a result of this different bonding, water molecules from γ-CD are released upon annealing in 2–3 successive stages

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• . Across all tested substrates, nucleophilic attack predominantly occurred at the homobenzylic position, leading to the regioselective formation of clavam derivative with 2-benzylic substitution due to aryl stabilization of the radical intermediate (see mechanistic discussion below). We briefly

• •] = +2.09 V vs SCE) [55][56]. The *PC+ species can oxidize the unsaturated lactam, thereby producing the corresponding radical cation intermediate A. The low stabilization by amide-bond resonance of the cyclic four-membered β-lactam [57][58] ensures a good nucleophilicity of the nitrogen atom to efficiently

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• 15: d = 2.356 Å) and with F3 and H4 (13: d = 2.867 Å, 14: d = 2.849 Å, and 15: d = 2.886 Å). Does the halogen at C4 contribute to the stabilization within the crystal lattice? To answer this question, we have to look at the behavior of halogens as hydrogen bond acceptors (X···H) and nonbonding

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• enhancing the reactivity of a relatively inert acceptor does not necessarily lead to increased reaction rates, involves the use of more reactive nucleophiles. In this context, varying the stabilization energy of carboxylic acid derivatives by switching from oxoesters to thioesters is the significant

• acceleration of the reaction progress [26][27]. The crucial enhancement of anion stabilization by deprotonation of the methylene group in bisthiomalonates was hypothesized to surpass that of analogous dibenzyl malonate [28][29]. Surprisingly, the employment of NaH, NaSEt, or t-BuOLi as relatively strong bases

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

• stabilization of the secondary nitrogen atom attenuates the nucleophilicity on the secondary nitrogen, furnishing regioisomeric product 103. This latter inverse regioselectivity is typical for arylhydrazines, and due to a lower overall nucleophilicity, often forcing conditions for the cyclocondensation are

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• stabilization, nucleophilicity would dictate regioselectivity outcomes. This also implies that the favorable NCIs and chelation are stronger driving forces towards transition-state energy partitioning than nucleophilicity alone. These results suggest chelation is a highly plausible driving force for

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

• containing an aromatic ring or heteroatoms (54, R2 = NHAc, NH2) were used, while aliphatic amidines (54, R2 = H, CH3, CF3) were unsuccessful, indicating that the resonance stabilization of the amidine was crucial to the reaction. Finally, Guillaumet et al. [55] have proposed a simple way to synthesize the 2

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• -) derivatization of aromatic scaffolds because it can be exploited to stabilize the longer (hetero)acenes. In contrast to cata-benzannulation, cata-imide-annulation does not perturb aromaticity patterns and further introduces inductive stabilization of frontier MO levels, which has enabled the production of n-type

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• stronger fatigue effect was observed in the photoisomerization of DA7 and DA6, this might be attributed to stabilization through hydrogen bonding and a favored cyclized-isomer in polar solvents. The increased alkyl linker length of DA10 and DA11 provided an improved photostability compared to DA7 and DA6

• , possibly due to the reduced stabilization and improved fatigue resistance of the cyclized-isomer in a polar environment. Photochemical properties of DAn in aqueous medium Delighted by the good photoswitchability performance of DAn in organic solvent, the photochemical properties and supramolecular assembly

• screening of DA11 and stabilization as macroscopic soft scaffold. Under an optical microscope, a deep-blue string with a diameter of ≈560 μm was observed in the macroscopic soft scaffold of DA11 (Figure S9, Supporting Information File 1), without any birefringence under crossed polarizers. A macroscopic

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• delocalization is considered to be secondary [7]. However, stabilization via intramolecular hydrogen bonding does not seem to significantly impact the conformational stability of 3-fluoropiperidine. In this context, the cis-conformer, with the axial fluorine atom facing the N-hydrogen atom, is either equally or

• -Lewis (electron delocalization) contributions, 17 and 19 were favored by a delicate equilibrium between weak repulsion and substantial stabilization due to hyperconjugation. Conversely, structures such as 9 and 10 experienced minimal steric effects but were inadequately stabilized by electron

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• applications [27][28][29][30]. For example, hypervalent bromine(III) reagents enable C–H amination and alkene aziridination reactions without the need for additional Lewis acid activation [31][32][33]. However, challenges in the synthesis and stabilization of cyclic hypervalent bromine and chlorine reagents

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• from the NCI plots. In general, stabilization of some 5-7 bicyclic carbocations (e.g., F-OH and H-OH) are via C+···OH interactions, which are facilitated by the carbocation and hydroxyl functionality being located in the relatively flexible 7-membered ring. This type of interaction is absent in case of

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• phenyl substituents, have been synthesized and shown to adopt non-planar conformations with the ortho-alkyl groups located above and below the most reactive 1,3-carbons of the furan ring. These bulky substituents provide a strong measure of kinetic stabilization. Thus, 1,3-dimesitylisobenzofuran and 1,3

• photooxidative resistance, especially along the acene-like segment, plus a strong measure of kinetic stabilization at the 1,3-carbons of the furan ring. As described here, there are compelling reasons to contemplate the synthesis of large, persistent isoacenofurans with unusually small HOMO–LUMO gaps. In this

• isoacenofurans. Thus, unless there is a need for improved kinetic stabilization of the most reactive 1,3-carbons on the furan ring, there appears little benefit of utilizing highly hindered 2’,4’,6’-triisopropyl (compound 24) or 2’,4’,6’-tri-tert-butyl (compound 25) substituents, especially as these compounds