Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• rest of the molecule. The transition state for the thermal back-isomerisation of 72 is planar in case of electron-donating groups and twisted for electron-withdrawing groups; the latter isomerise faster than the former (Scheme 23, top). The planar transition state is also favoured in polar and protic

• -position give hypsochromic shifts and shorten the thermal half-life by stabilising the transition state 73’ (Scheme 23, bottom) [63]. Synthesis The classic synthesis of indigo is achieved via Baeyer–Drewsen synthesis reacting 2-nitrobenzaldehyde (74) and acetone in basic medium (Scheme 24, top) [91]. Since

• transition state E-inversion (Scheme 32A). The addition of ring strain between the stator and the rotor (Scheme 34, right) was found to affect the thermal half-life depending on the ring size [109]. Too small (n = 3) 108a and too large rings (n > 5) 108d–f force the E-isomer in a less stable conformation and

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

• based on NO2+. The intrinsic kinetics model based on NO2+ can be established as shown in Table 3. According to the Brønsted–Bjerrum rate law (transition-state theory) [62], the overall rate equation based on NO2+ can be transferred into an activity coefficients-based rate equation. According to the

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

• Israel Fernandez Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040-Madrid, Spain 10.3762/bjoc.21.125 Abstract The influence of transition-state aromaticity on the barrier heights of concerted pericyclic reactions is summarized herein. To

• other than aromaticity govern the barrier heights of these pericyclic reactions. Keywords: activation barrier; activation strain model; aromaticity; computational chemistry; transition state; Introduction Aromaticity is arguably one of the most fundamental and extensively studied concepts in chemistry

• 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

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

• calculated the distance between the imino carbon atom and the nitrogen atom of the NMe₂ moiety (d) for local minimum and transition-state structures (Figure 2). In the local minimum and transition state of the C–N rotation and C–N/C–C concerted rotation, protonation leads to a shortening of the C–N bond by

• double-bond nature of the C–N bond in the transition state of the C–N/C–C concerted rotation was decreased due to the twisted structure, and the activation energy varies depending on whether the amidine was protonated or in its molecular form (Figure 2). To investigate the effect of protonation on the

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

• , the racemization barrier of 5 (34.8 kcal mol−1) is larger than that of CBBC 1 (33.7 kcal mol−1), which accords with the experimental results. In the transition state TS2, the exocyclic olefin unit a is close to the adjacent benzene ring b, which causes intramolecular steric repulsion to increase the

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

• conventional UV–vis spectroscopy, suggesting preferable population of intramolecular hydrogen bonding stabilized E. Comparing the angles α of the E* form (13°) and the transition state between E and Ecis (60°) the former is nearer to the geometry of E, suggesting preferable population. The excitation of KE

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

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

• activation energy modulation during transition state formation. Specifically, donor/acceptor electronic configurations in the substrate could either stabilize or destabilize the transient hybrid state, thereby thermodynamically governing the energy barrier for intermolecular HAT progression. When the partial

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• structure on the potential energy surface is located, which can be done straightforwardly using standard optimization algorithms. While the use of intermediate energies provides a computationally efficient alternative to explicit transition state searches, it rests on the assumption that there is a

• the transition state [10][11]. The site with the lowest reaction energy is expected to correspond to the experimentally observed reaction site. Therefore, instead of locating the structure of the transition state, the preceding palladacycle intermediate structure is generated and optimized, as shown

• theory or perform a transition state search to calculate the activation energy. With this threshold, we obtain 70% correct, 14.5% semi-correct, and 14.5% wrong predictions over the whole dataset. For six out of 17 molecules, all possible reaction sites are predicted as reaction sites within the threshold

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• . A comprehensive DFT investigation of reactant 6 was carried out to analyze the transition state of the IMDA reaction for a Br-substituted diene and its charge distribution (Figure 2). The diene has a notable positive charge (+0.318, +0.098, 6a), (+0.334, +0.082, 6h) and (+0.316, +0.074, 6r) whereas

• calculated using the Gaussian 16 software (Figure 3) [21]. The N-acylated compound 6a has a baseline relative energy of 0 kJ/mol, while the transition state of the Diels–Alder (TS-DA) reaction presents the highest energy barrier at 1.221 kJ/mol. The DA adduct shows a little lower energy at 1.001 kJ/mol

• , indicating a smooth transition from the transition state to the product. The final dehydrative ring-opening gives products by decreasing the energy to 0.978 kJ/mol. Computational analysis indicates that the IMDA step has a high energy barrier which needs a catalyst, while the dehydrative re-aromatization

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• carboxylate groups followed by a ring opening of the aziridine ring, forming azomethine ylide intermediates A. The intermediates A further undergo a [2 + 3] annulation (or cycloaddition) with aldehydes 2 through endo transition state TS to generate intermediates B, which release products 3 with regeneration

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• relaxation into the CT D1 state, from where emission back to the D0 ground state may occur. Weak donors will exhibit a high energy transition state to crossover from the excited LE to the CT state (large ΔGCT‡, point 1 in Figure 9). In absence of any excess energy, the LE will relax non-radiatively to the

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• single product, with no detection of 34 (Table 1, entry 11). This result presumably arises from the minimization of dipole–dipole repulsions between the carbonyl of the dienone moiety and the C14-OMe within the desired transition state (more details were discussed in our group’s previous work [29

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

• addition to a second molecule of 1. Given the negative results observed for other crotonate derivatives (Scheme 3c), coordination between the Li cation and the two chlorine atoms via proposed transition state D may be crucial not only for diastereoselective control but also for the viability of this step

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• involvement of a triplet state mechanism, which crosses the transition state for the Z→E relaxation, could explain the low values of the activation entropy. The same authors also showed experimental evidence for this proposal by an external heavy atom effect on Z→E isomerization. To understand the thermal Z→E

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• involves the regioselective nucleophilic attack of allylaluminum C on tosyl cyanide, which proceeds at the γ-position via six-membered ring transition state D, leading to the formation of the desired nitrile product. Transition state D is responsible for the E-selectivity observed in trisubstituted allenes

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

• later stages of the catalytic cycle, are less likely to racemize without bond breaking. The barrier to pyramidal inversion has been found to be 15.1 kcal·mol−1. Berry rotation itself proceeds via a tetragonal pyramid as transition-state structure and does therefore not occur here. A second isocyanide

• bond. One of the most important quantities which allows comparison with experimental data is enantioselectivity. The most favorable TS 9-10 is that which leads to the "S"-configured product, when the substrate is Z-hydrazone. Product of opposite handedness is reached via a transition state, 1.0

• kcal·mol−1 higher in energy, resulting in a theoretical ee value of 74% (at 263 K), if pure Z-hydrazone would be used and under the assumption of kinetic reaction control. In contrast, the E-hydrazone gives preferably the "R" product (with a theoretical ee value of 64%). The transition state which gives

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

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

• ligand L3 and the allylic electrophile 35. In contrast, a si-face attack leads to a higher-energy transition state due to significant steric repulsion. Enantioselective hydroallylation of vinyltrifluoromethyl compounds The direct functionalization of 1-trifluoromethylalkenes 38 through copper catalysis

• transition states: an open transition state TS7 facilitated by LiOt-Bu and a closed transition state TS6 without base assistance (Scheme 17a). The significant energy difference between these pathways (ΔΔG‡ = 4.3 kcal/mol) strongly favors the open transition state TS7 mechanism, attributed to reduced steric

• energy compared to (S,S)-TS9. Both transition states demonstrated a lithium center's coordination involving bromide, benzoate, and ligand oxygen atoms. The (S,R)-TS8 transition state exhibited a significantly shorter Li–Br interaction distance (2.81 Å compared to 3.74 Å in (S,S)-TS9), offering

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

• groups) with little [73], if any, transition-state binding [36][80][81]. Thus, these macrocycles depend on the catalytic concept of organization; polarization is a minor contributor. Size-exclusion and regioselective outcomes are possible [56][82][83][84][85], and symmetric arrays of chiral units (like

• generated large electrostatic effects by functionalizing the capsule exteriors with charged groups (Figure 4D) [136][137]. Observed rate accelerations for capsule-promoted nucleophilic substitution reactions demonstrate significant enthalpic stabilization of the transition state attributable due to the

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

• pathway through an associative transition state to form the equatorial glycoside, 7. Surprisingly, recent evidences show that typical homogeneous glycosylation reactions in organic solution shift more towards the SN2 end of the mechanistic spectrum [32][33][34], with some exceptions [35]. The kinetic

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• transition state for N1–N4 and I1–I4 using various functionals in combination with a 6-31G(d) basis set. The theoretical activation free energy (ΔG‡(calc)) at 298 K was determined as the difference in the sum of electronic energy and thermal free energy correction between the closed-ring isomer and the

• transition state (see Tables S7–S14 in Supporting Information File 1). Table 2 shows the differences in ΔG‡ between the theoretical value obtained by DFT calculations and the experimental value, i.e., ΔG‡(calc) − ΔG‡(exp). The B3LYP and M05 functionals underestimated the ΔG‡ value, while the BMK, CAMB3LYP

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• in a formal oxidative addition to form benzofuranylnickel(II) fluorides F, which then undergo transmetallation with arylboronic acids 2 to produce intermediates G (Scheme 5, path b). Alternatively, a direct transition from E to G via transition state H is also possible (Scheme 5, path c). Ultimately

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• . Transition-state calculations gave insight into possible reaction pathways. CPA C48-activated substrates react and rearomatization of the benzene ring leads to the intermediate Int-66. In the presence of an oxidant, axially chiral product 213 is formed. Otherwise, nitrogen-initiated intramolecular