Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• difference between TS1 and TS2 (4.7 kcal/mol), compared to that between TS3 and TS4 (6.9 kcal/mol), can be attributed to hydrogen-bond stabilization in TS2, indicating that conformational effects play a more dominant role than hydrogen bonding in determining transition-state stability. Mulliken charge

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• still observed in the measurement at 5 °C, albeit only slightly. The phenyl-substituent effect on the stereochemical stability can be understood as a destabilization of the ground state due to the transannular repulsion, and a stabilization of the transition state for racemization by a conjugation

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• affect the cycloaddition by, for instance, binding copper cations or counter anions, and thus their presence in the structures of calixarenes at the CuAAC step must be avoided. On the other hand, the unmodified amines may also contribute to undesired Cu(I) stabilization and complicate the CuAAC work up

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• very existence of a chiral architecture constitutes a discovery in itself. The identification and stabilization of unconventional stereogenic elements expand the accessible chemical space, prompting us to reconsider what forms of molecular asymmetry are possible, meaningful, and exploitable

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• , bioactive molecules, and advanced materials. However, its exceptional resonance stabilization renders the C–N bond highly inert, posing a persistent synthetic challenge for its transformation. While twisted amides with distorted C–N bonds have offered useful reactivity enhancements, the selective activation

• . Conclusion This review has highlighted major advances from the past decade in the activation, cleavage, and transformation of non-activated amides. Although the amide bond is fundamental to chemistry and biology, its exceptional resonance stabilization renders it remarkably resistant to nucleophilic acyl

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• preferential formation of the endo-adduct (upper pathway). The predominance of exo-isomers in some cases probably reflects insufficient stabilization due to secondary orbital interactions in the transition state [43]. It should be noted separately that secondary cyclic amino acids such as azetidine-2

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• arene activation offers powerful opportunities in reactivity design. Notably, the small-ring annelation exerts a dual influence: it lowers kinetic barriers and enhances regioselectivity, with strain-release providing the key thermodynamic driving force to overcome aromatic stabilization. Synthetic

• principal platforms. Distinct from their η3-allyl counterparts, which readily isomerize between σ (η1) and π (η3) coordination, the η3-benzyl motif demands partial disruption of aromatic stabilization – an energetic penalty that must be compensated by the metal–ligand interaction (Scheme 5A). This challenge

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• preference arises primarily from hyperconjugative stabilization, particularly the σCH → σ*CN interaction, while steric effects modulate the relative stability among low-energy conformers. The gauche effect is intensified in the zwitterionic form due to electrostatic interactions. In contrast, the

• geometry, gain less than 500 kcal mol−1 from delocalization, whereas the most stable structure (1) is stabilized by 502.6 kcal mol−1. Notably, structure 5 (type II) is also strongly stabilized by delocalization (ENL = −501.7 kcal mol−1), while structure 2 shows weaker stabilization (−496.2 kcal mol−1

• ). These results indicate that the gauche effect in DFMO arises from a balance between strong non-Lewis stabilization and only moderate Lewis-type destabilization. Further insight was obtained by examining specific hyperconjugative interactions through second-order perturbation analysis. In 1,2

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• the presence of a specific crystalline packing motif that allows for effective intermolecular interactions and the stabilization of triplet excitons, which are necessary for phosphorescence to occur at room temperature. To investigate the packing arrangement necessary for the manifestation of RTP in 1

• , facilitated by the π–π interactions between adjacent molecules, plays a key role in the stabilization of the triplet state, which in turn contributes to the observed room-temperature phosphorescence. This finding underscores the critical role that molecular arrangement and packing have in governing the

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• catalyst–ligand systems to overcome higher aromatic stabilization energies. Thus, chemoselectively distinguishing between partial and complete reduction is crucial: depending on the substrate, the catalyst must either halt the process at a defined stage or drive it to full saturation without affecting

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• principle [38]. At least, the reaction times and conditions required for the alkylation reactions investigated, which proceed through an α-attack, indicate relatively high barriers. This in turn indicates that the selectivity observed in alkylation reactions (α-attack) is due to some stabilization of the

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• which leads to the formation and stabilization of the three-membered cyclic carbocation (Int4). The electron-donating group provides electron density to the carbocation, which stabilizes the positive charge. As a result, Int4 is observed when electron-donating groups are present (Scheme 2). In Int4, the

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• observed, however, with an increase in fluorescence emission. Interestingly, in DMSO, a bathochromic effect was observed alongside a significant increase in fluorescence intensity. In aqueous medium, a pronounced red shift was verified, likely due to stabilization of the excited state by water molecules

• Figure 7d and Figure S251d in Supporting Information File 1 provide data on the stabilization mechanism in the excited state in relation to the ICT process and the polarity of the solvent [90][91]. The graphs were generally linear, demonstrating that ICT-type mechanisms were favored for these compounds

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• containing functional groups in the linker including an amine (Db1), an amide based on the V linker (Db2), and an aniline (Db3). In the case of Db1, physiological conditions would afford a protonated amine functionality that may allow for stabilization of the triplex through electrostatic interactions

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• van-der-Waals interactions between phenyl rings of the benzoate substituents are crucial for the stabilization of the furanoside isomer. This outcome could not be rationalized within the framework of conventional carbohydrate chemistry, as the key intramolecular interactions determining the

• possible similar transformations for glucosides and mannosides [28]. The stabilization of the furanose form was facilitated by the bulky and charged sulfate groups, leading to repulsive interactions (Figure 2B) [24]. This effect was observed across various configurations, such as galacto-, gluco-, fuco

• -, arabino-, and xylo-. However, for both α- and β-mannosides, pyranoside form remains the favorable one. In another study [26] the presence of two bulky silyl substituents (TIPS or TBDPS) at the O2 and O3 positions of galactose also resulted in stabilization of the furanoside product (Figure 2C). Another

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• form three possible products: ketone 191, olefin 192, and cyclopentane 193 (Scheme 33). At the first stage, the epoxy ring was opened to form intermediate A. According to the authors [87], there are three possible ways of carbocation stabilization. The 1,2-shift of a proton at C3 to C4 led to the

• in the stabilization of cationic reaction intermediates [91][92]. Yokoshima and co-workers [93][94] developed an elegant approach to the total synthesis of the alkaloid huperzine Q (206) in racemic form (Scheme 37). In the process of synthesis, a cis-hydrindane core was prepared from the known

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• electron transfer for zwitterionic intermediate (e.g., (−)-106b or (+)-106b) formation; (2) protic solvents (e.g., MeOH) improve ee values through H-bonding stabilization, which reduces intermediate flexibility; (3) low temperatures enhance the optical purity by slowing conformational changes without

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• regulatory role in chemical transformations, exerting kinetic modulation through solvation effects on activation barriers and reaction rates, dictating thermodynamic equilibria that govern product distribution, and enabling precise reaction pathway regulation via selective stabilization of critical

• assembled the pentacyclic spiroindole framework 61 (Scheme 13, path b). The controllability of this cyclization process arose from the steric and electronic effects of the aryl group, where the π–π interactions and rigid structure of the aryl group facilitated the stabilization of the five-membered spiro

• cyclization, yielding a six-membered ring product 72 (Scheme 15, path b). This observed selectivity arose from differential stabilization of transition states by ligands, thereby enabling the Au(I)-catalyzed cyclization to directly access bioactive heterocyclic frameworks commonly encountered in natural

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• species C benefitting from additional stabilization by virtue of electron delocalization onto the NHC-derived azolium ring [17][18][19][20]. Similarly, the cationic azolium fragment in acylazolium salts can effectively lower the carbonyl reduction potential relative to the starting material with single

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• stabilizing due to the presence of two anomeric-like interactions, nF → σ*CF [16]. According to a natural bond orbital (NBO) analysis, this electron delocalization accounts for a stabilization energy of 14.3 kcal mol−1 per interaction in compound 1.1. Similar stabilization values are observed in other

• dipolar repulsion compared to 1.2-t. and receives less stabilization from electron delocalization. The electron delocalization interactions in these systems are primarily syn- and antiperiplanar σCH → σ*CF interactions. Although the latter is more stabilizing and more prevalent in 1.2-c, the overall ENL

• stable than 1.2.3-c.t., this is not due to a higher EL term but rather to less effective stabilization from electron delocalization interactions. This finding is somewhat surprising, as one might expect 1.2.3-c.c. to exhibit greater steric and dipolar repulsion involving the polar C–F bonds. Finally, a

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

• donors [65][66], care must be taken, and glycosylation conditions optimized to avoid the formation of oxocarbenium ions from TMS-glycosides intended to function as glycosyl acceptors. In this case, the ketoses 49 and 52 formed the oxocarbenium ions more readily due to stabilization by their alkyl

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

• a stabilization energy of ca. 17 kcal/mol. In the alternative hyperhomodesmotic reaction B, defined as 5 + 6 → 7 + 1, the formal ten-electron Hückel aromaticity of the imidazo[1,2-a]pyridine moiety (in blue) was preserved while the phenyl component was decomposed. The computed stabilization energy

• of this second reaction was calculated to be of 28 kcal/mol, slightly lower than the aromatic stabilization energy (ASE) and isomerization stabilization energy (ISE) calculated for benzene [20] (see reaction D in Scheme 1). Most likely this lowering stems from the strain imposed to the ortho

• -phenylene moiety in the tetracyclic structure. Combination of reactions A and B in the form yields an average value of ⟨ΔEAB⟩ = −22.6 kcal/mol. A similar treatment of the separate components as outlined in reactions C and D shows a much lower stabilization energy for imidazo[1,2-a]pyridine 8 and a higher

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

• further support to the barrier-lowering effect induced by the aromaticity of the transition state. While the purported ‘‘aromatic stabilization’’ is mainly established based on comparisons to transition states of alternative stepwise reaction routes, its extension to highly related processes following

• used in the synthesis of a good number of target molecules, including complex natural products [32][33][34][35]. Typically, the LA binds the dienophile through a donor–acceptor interaction (usually involving a carbonyl group) which results in a significant stabilization of the dienophile’s LUMO. As a

• aromatic species. Although aromaticity and energetic stabilization are traditionally connected in stable species (i.e., minima on the potential energy surface), it is found that processes featuring more asynchronous (less aromatic) transition states exhibit lower barriers than their more synchronous

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

• the donor property but also to lower the energy of the LE state of the PTZ moiety. Notably, while PTZ adopts a non-planar conformation in the ground state, it undergoes planarization in the excited state [16][17]. This conformational change is expected to further enhance the stabilization effect

• imparted by TPA. Such stabilization could bring the energy levels of the LE state of the PTZ moiety and the CT state into closer proximity, which may create conditions favorable for establishing a transient thermal equilibrium between the LE and CT states. In this study, we designed and synthesized a

• driven by the enhanced electron-donating ability of the TPA units, but rather by the stabilization of the PTZ 1LE state, which is facilitated by planarization of the PTZ moiety in the excited state and the resulting increase in π-conjugation. This behavior led to the persistent presence of 1LE-state

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• axially chiral anilines [10][11] and a triazine molecule [9]. In particular, protonation of a remote basic site in N–C axially chiral anilines significantly increases the rotational barrier by attenuating resonance stabilization in the transition state. One important issue in this field is the development