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

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• the synthesis of oxindoles (Scheme 43) and isoquinolinediones (Scheme 44) [26]. In this work, visible light was used to promote a single-electron-transfer (SET) process, overcoming the inherent challenges associated with activating the strong C(sp³)–Cl bond, which typically requires high activation

• energy (327 kJ/mol) and is less reactive compared to alkyl bromides or iodides. Previous methodologies predominantly relied on alkyl bromides and iodides due to their lower bond dissociation energies. By leveraging the excited-state reactivity of Pd(0) complexes under blue LED irradiation, this method

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

• Chen et al. [4]. We are excluding cyclization reactions for which the regioselectivity is not only determined by the activation energy to form the palladacycle intermediate but also by which site is accessible for the intramolecular cyclization. Using the previously described workflow, we were able to

• . The wrong prediction here might indicate that the BEP relationship does not hold in this case and one would need to calculate the activation energy of the actual transition states. Molecule 3 from Jiang et al. [28] is another intramolecular cyclization reaction which was not labelled as such. For such

• reactions, the regioselectivity is not only determined by the activation energy for the rate-determining step but also by the proximity of an intramolecular reaction partner, here the secondary amine. From this in-depth analysis, we conclude that our QM workflow only predicted the wrong reaction site for

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

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

• while regenerating the catalytic species Int-82. Comparative kinetic analysis revealed a marked preference for alkyl iodide activation, as demonstrated by its substantially lower activation energy barrier compared to alkyl bromide analogs (path b). This energetic advantage facilitates preferential

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

• theory in combination with the 6-31G(d) basis set well reproduces the experimental value of the activation energy for the thermal back reaction of various diarylbenzenes, resulting in the accurate prediction of the half-lifte time [58][63]. Thus, the combination of experiments and theoretical

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• ° and C–I bond lengths of 2.1 Å (I–CH2CF3) and 3.2 Å. Finally, a 37.8 kcal/mol activation energy between XB-2 and B for path 1 was calculated. On the other hand, path 2 had a much lower Gibbs free energy of activation of 24.3 kcal/mol, where the angle of attack from 1a to 2a’ was found at approximately

• 160° with equal C–I bond lengths of 2.5 Å in the transition state. The significantly lower activation energy allowed us to conclude that the SN2 mechanism was the more favourable pathway. Conclusion In conclusion, we have developed a direct polyfluoroalkylation reaction of sulfoxonium ylides. The

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• and 7a are formed (Scheme 4). Although intermediate 7a has a lower activation energy (∆G = −0.23 kcal/mol), further recyclization processes are not possible due to the positive free energy change (∆G > 0). In this context, the formation of the final product is only possible to proceed via intermediate

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• transition state is not stabilized, leading to the increase of the activation energy of the reaction. As a result, the reaction does not proceed smoothly. The absolute configurations of product (S)-23c, (S)-23d, and (S)-23e were determined on the basis of their X-ray crystallographic analyses. The validity

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• ][27]. The previous plots are effective for metal-based catalysts and relatively simple catalytic reactions; however, they fall short when reactions involve multiple steps and independent activation barriers. In this paper, instead of focusing solely on the activation energy, the energy span of the

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• ]. Most of the existing methods were originally designed for predicting reaction properties (such as activation energy, reaction enthalpy, etc.) or classifying reactions, but they can be potentially adapted for reaction conditions prediction by modifying the output layer of the model. Both global reaction

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• modeling of this reaction was performed based on the theory of NO2+ attack, with the activation energy and pre-exponential factor determined. Finally, based on the response surface generated by the kinetic model, the reaction was optimized with a conversion of 87.4% under a sulfuric acid mass fraction of

• values of k0 at different temperatures, the activation energy for the electrophilic attack of NO2+ on the IO can be calculated by the Arrhenius equation: where R is the molar gas constant and T denotes the temperature in Kelvin, and Ea and A are the activation energy and pre-exponential factors for the

• temperatures on the apparent rate constants can be understood. In addition, a complete kinetic model of IO nitration based on NO2+ was developed to describe the reaction process, the activation energy of the IO nitration was calculated to be 192.57 kJ/mol. Furthermore, the accuracy of the kinetic model was

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• followed a second-order reaction. Since no monoadducts were formed, the rate-determining step is the first azide addition. Based on this fact, the activation energy (Ea) of the reaction between 5 and benzyl azide in CDCl3, determined by the Arrhenius plots, was 60.9 kJ mol−1 (Figure 3). This value was

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• activation energy may allow for oxy-Cope rearrangement at 28 °C. DFT calculations (in toluene) of 5-hydroxyalbireticulene for both the pseudo-axial and pseudo-equatorial conformations of the C5 hydroxy moiety suggest that there is not a significant difference in the free energy barriers for the oxy-Cope

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• photoswitching cycle. The activation energy required to trigger the transformation of the metastable photoisomer to the parent diene is called the thermal back isomerization barrier. The TBR barrier governs the duration of storage of harvested solar energy in the MOST devices. Photoswitching systems exhibiting a

• DFT-based PBE method is still better to predict the geometry of TS using nudged elastic band (NEB) calculations and multireference methods determines the activation energy values close to the experiments [42]. In the present investigation, the geometry of all the TS structures was obtained with the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• C–H bonds into the alkene π-bond [30]. Before reviewing polar hydrochlorination reactions in detail, it is worth mentioning several statements which were made in the Sergeev review [12]: a) The activation energy for an anti-Markovnikov addition is at least by 30 kJ mol−1 higher than for normal

• concerning the polar hydrochlorinations the activation energy for an anti-Markovnikov addition is at least by 30 kJ mol−1 higher than for normal addition. Therefore, the formation of the anti-Markovnikov product via purely cationic intermediates is never observed. The only report for the formation of the

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• ). The other two isomers, 2 and 3 (Figure 5b,c), with two CPPs tilted at 15.6° and 45.5°, are 2.5 and 4.2 kJ mol−1 less stable than complex 1, respectively. The stability among the isomers is low, and the activation energy for isomerization should be very low. Therefore, all isomers are expected to be

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• behavior was explained by the large energy gap between the ground states of the E- and Z-forms of indigo as well as low activation energy of inversion for derivatives 13. In the same year, Nielsen, Hecht and co-workers achieved a remarkable stabilization of the Z-isomer of N,N'-disubstituted indigo 24 by

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• possibility of through-space interactions with prenyl side chains using DFT calculations. Our calculations show that (i) the unstable secondary carbocation is stabilized by the cation–π interaction from prenyl side chains, thereby lowering the activation energy, (ii) the four-membered ring formation is

• interacts with the secondary carbocation at C10, reducing the activation energy of the first step by approximately 4.7 kcal/mol. Moreover, due to the stabilization of the secondary carbocation-like intermediate IM2, the reaction proceeds stepwise rather than concertedly [7]. It was found that the final

• the stabilization of the intermediate IM2b is greater in path b, the activation energy suggests that path a is more favorable. Generally, the activation energies for terpene cyclization reactions are often below 10 kcal/mol. However, in the case of complex rearrangement reactions involving secondary

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• and regenerates the tert-butoxyl radical to complete the entire catalytic cycle. The formation of hydrogen bonds between the oxygen of the carbonyl group and the hydrogen of the 2,2,2-trifluoroethanol (TFE) reduces the activation energy of the radical reaction and improves the coupling efficiency. In

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. Computational investigations were conducted to better understand these reactions, and it was determined that the changing alkyl motif (e.g., dimethyl, cyclopentyl, adamantyl) had minimal impact on the activation energy of the fluorination reactions. The reaction coordinate was calculated for Meldrum’s acid

• comparing ylides 31 and 70 in this reductive elimination step, which suggested that the ortho-nitro group of 72 (and 71, by extension) played a role other than lowering the activation energy of this step. Given that other optimized halogen- and hydrogen-bonded conformations were found between thioamide and

• . Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation. Mechanistic proposal for the X–H insertion reactions of iodonium ylides. Calculated reaction coordinate for the radiofluorination of iodonium ylide 60. Difference in Gibbs activation energy for ortho- or para-anisyl

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• Gibbs activation energy of enantiomer 53 for the racemization process was determined as 33.0 kcal mol−1 at 298 K. The CPL spectra of M-53 and P-53 showed an emission maximum at 560 nm with glum value of 2.3 × 10−4. Instead of helicene formation in the final Scholl-type ring formation step, Martín and co

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• model [30] the distortion energy (ΔE≠d) corresponds to the difference between the single point corresponding to interacting 3 and 4, and the sum of single-point calculations for TS2-a and TS2b. The apparent activation energy (ΔE≠app) refers to the energy difference between TS2 and the interacting

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• activation energy supported the proposed routes (see Supporting Information File 1 for details). Conclusion In summary, a borane-catalysed hydroboration of nitriles to give primary amines has been developed, transforming the previously stoichiometric reagent H3B·SMe2 into a catalyst. B-N/B–H transborylation