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

• meaningful correlation between thermodynamic stability and kinetic accessibility, as expressed by the BEP principle. Although this principle has been successfully applied in many cases, the correlation between reaction energies and activation barriers is often imperfect. For instance, studies on hydrogen

• atom transfer and cycloaddition reactions have reported correlation coefficients (R2) of around 0.7 at best, indicating significant deviations from ideal behaviour [12][13]. This means that even when intermediate energies are accurately computed, the predicted regioselectivity may still carry a degree

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• ). This significant energy difference supports the observed stronger binding of Li+ in these systems. The higher binding constant for the Li+ cation is consistent with the correlation between binding constants and binding energies for a 2:1 model [25]. Conclusion In conclusion, we have explored the

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

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

• found. We thus suspect that the substituents play a crucial role in in the population of the respective exited state and we can at this state not rule out a contribution also from the triplet state. Moreover, we could not find a quantitative correlation between the R-substituents and ΦE→Z, however, some

• →E ). Strong EWGs or EDGs enhanced the quantum yields for the π→π* transitions, whereas the n→π* transitions exhibited no clear correlation with substitution patterns. Notably, the acetylation of nitrogen significantly increased the ΦE→Z for π→π* transitions in almost all compounds studied (excluding

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

• ). Furthermore, the 2D 1H–13C HMBC NMR spectrum of 5a also exhibited the correlation between protons of two methyl groups and the same carbon atom resonance at 165.52 ppm, respectively (see Supporting Information File 1). Consequently, the signal at 165.52 ppm in the 13C NMR spectrum corresponds to the sp2

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• unknown photoisomer (N-UnS1). Structural investigations using exhaustive 2D-correlation NMR spectroscopy were also inconclusive. Next, the push–pull functionalized derivatives O-NBD2 and N-NBD2 were investigated. Notably, N-NBD2 exhibited the most pronounced red shift (Table 1) and was the only nitrogen

• potential further rearrangements or photodecomposition. To gain a better understanding of the ongoing conversion processes, we conducted NMR spectroscopy. The assignment of individual proton signals was supported by 2D correlation NMR spectroscopy (Supporting Information File 1). First, O-NBD2 is

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

• the computational investigation, could not be isolated either – probably due to its high sensitivity to hydrolysis. However, a 2D 1H-15N NMR correlation spectrum showed no interactions of hydrogen nuclei in silicon-bound methyl groups and any of the nitrogens in the product. This led us to conclude

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

• boronate complexes and correlation with reactivity. Copper-catalyzed stereospecific allylic alkylation of secondary alkylboronic esters via tert-butyllithium activation. Copper-catalyzed stereospecific allylic alkylation of chiral tertiary alkylboronic esters via adamantyllithium activation. DFT-calculated

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• confirmed the presence of these groups. The HMBC correlation from H-4 (δH 5.65, dd, J = 4.4, 1.0 Hz) to C-1'' (δC 165.7) and the upfield shift of H-3 (δH 3.98, dd, J = 5.1, 4.4 Hz) compared to the same proton in compounds 2–5 evidenced that the crotonyl moieties were linked at C-4 and C-7. Compound 8 was

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• cryptophycins 1 and 2 showed high cytotoxicity with 313 pM (1) and 6.36 nM (2) and outstandingly low resistance factors. Furthermore, the new cryptophycin 1 confirms the correlation between degree of alkylation and cytotoxicity of m-chloro-p-amino unit B derivatives. Since MDR is responsible for over 90% of

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• that the enantiomeric ratio values in Table 5 correspond to the major anti-diastereomer. The absolute configuration of the significant diastereoisomer obtained in the kinetic resolution of compound 3 was established by chemical correlation with (2R,3S)-1,2,3-triphenylpentan-1-one (19), previously

• acetate mixtures as eluent. Experimental procedure for the chemical correlation of 3 with 19. In a Wheaton flask, 3 (53 mg, 0.16 mmol), 1,3-propane dithiol (21 mg, 0.19 mmol, 1.2 equiv), and scandium triflate (3 mg, 0.0064 mmol, 0.04 equiv) in CH2Cl2 were mixed, and the resulting mixture was stirred for

• : hexane/ethyl acetate 2:1), obtaining 19 (19 mg, 0.06 mmol, 50%). Previous work. Hypothesis, retro-Michael reaction, and its application in kinetic resolution. Model reaction. Kinetic resolution of the Michael adduct 1. Chemical correlation of 3 with 19. Epimerization of the anti-1 adduct promoted by A

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• transformation from a conceptual standpoint. Another fundamental law in photochemistry is the Beer–Lambert law, which describes a negative exponential correlation between the transmittance of a solution containing chromophores (i.e., a light-absorbing species) and the optical path length (Figure 1). In essence

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

• correlation between Ep of the redox event and the square root of the scan rate (Scheme 3B) suggested that compound 4a is not significantly adsorbed on the electrode surface [23]. Comparison of the jp vs v0.5 slope with our previously obtained results for the anodic oxidation of aryl bromides 6a (two-electron

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

• reaction of o-chloranil with benzoannelated derivatives of 2,3,3-trimethylindolenine, a comprehensive evaluation of the structure of the compounds obtained using quantum chemical methods, X-ray diffraction analysis, two-dimensional correlation NMR spectroscopy, as well as investigation of their ionochromic

• proton is shifted to a stronger field of 14.23 ppm and appears as a narrow singlet (Supporting Information File 2, Figure S17). Analysis of two-dimensional correlation spectra of heteronuclear NMR spectroscopy shows that compound 7a in DMSO-d6 solution exists in the (NH) tautomeric form. Thus, in the 1H

• spectrum of 7a, a correlation of the NH proton with the bridging carbon atoms C(3a'), C(9b'), and the quaternary carbon atom C(1') of the indolenine fragment is observed with δH 136.6 ppm, 134.0 ppm, and 53.6 ppm, respectively (Supporting Information File 2, Figure S20). The most important HMBC

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• fungus Beauveria bassiana [11]. Further confirmation of the depicted structure of 1 was obtained via its HMBC spectrum (Figure 2, Figure S8, Supporting Information File 1) that revealed key correlations from the two aromatic protons H-5'/H-9' to the C-3' and in turn a key correlation for H-3' to the

• one doublet methyl group at δH 0.94 (d, J = 6.6 Hz, H3-15) indicating its presence in the middle between both methyl groups. The latter together with a terminal triplet methyl group at δH 0.80 (t, J = 7.4 Hz, H3-14) further revealed key correlation to one tertiary and one secondary sp3 carbon atoms at

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

• prediction of thermal back reactivity. Moreover, we attempt to find the optimal functional for achieving a high correlation with experimental values by DFT calculation. Results and Discussion Photochromic properties in n-hexane Compounds N1–N3 were synthesized according to the procedures described in the

• of the aryl group on thermal reactivity, providing a foundation for future molecular modifications. Furthermore, DFT calculations identified M06 and MPW1PW91 as the most suitable functionals for accurately predicting the thermal back reactivity of aza-diarylethenes, achieving a high correlation with

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• , respectively) and chloroform (α = 0.20 and β = 0.10) [51], ΔδDMSO–CD3NO2 and ΔδDMSO–CDCl3 should follow a similar trend. Our 1H NMR experiments showed a strong linear correlation between ΔδDMSO–CD3NO2 and ΔδDMSO–CDCl3 for neutral HB donors (R2 = 0.985, Figure S15 in Supporting Information File 1), confirming

• percent populations of Me3PO and the corresponding HB donor conformer as two non-interacting molecules (see Supporting Information File 1 for details). We found a strong linear correlation between ΔGexp and ΔGcalc obtained at the PCM(MeCN)-M06-2X/6-31+G(d,p) level of theory (Figure 5 and Figure 6A). These

• values. The predicted Gibbs free energy of binding (ΔGcalc) was calculated at the PCM(MeCN)-M06-2X/6-31+G(d,p) level of theory. The counteranion for all cationic species is BF4−. A) Linear correlation between ΔGexp and ΔGcalc. ΔGexp and ΔGcalc values are shown in Figure 5. B) Linear correlation between

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• shape transformation experiments are indicative of a clear correlation between the dehydration of the membrane and its susceptibility to change shape through osmotic shock (Figure 3). Besides this, one final evidence for dehydration of the PSar corona was provided by NMR in Supporting Information File 1

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

• -angle region, assigned respectively to as hch, for the disordered chains, and hπ, for the long-range core–core stacking resulting from strong polar–π interactions. The correlation length of the stacking was calculated by the Debye–Scherrer formula, which correspond to ca. 15–25 stacked molecules (Table

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• 2.43) and methylene carbon C-22 (δC 46.3), and between H2-22 (δH 3.73) and N-methylene carbon C-20 (δC 58.7), indicated that C-22 was connected to 20-N. Additionally, an HMBC correlation was observed between H2-22 and the non-hydrogen-bearing carbon C-23. Considering the chemical shift of C-23 (δC

• ]. Despite the absence of an HMBC correlation directly indicating a connection between C-8 and C-9, the HMBC correlation between the N-methylene protons H2-10 (δH 3.66) and the carbonyl carbon C-9 (δC 161.5), along with the molecular formula of compound 1 by process of elimination, suggested that C-8 and 9-N

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• 3.33, 1.91, 2.21), and a three-bond HMBC correlation from δH 3.33, and a two-bond correlation from δH 2.20 to the carbonyl resonating at δC 173.9 [15]. The observation of a 3JCH correlation from δH 3.20 to the nitrogen-bearing carbon at δC 46.4 and to δC 173.9 supported the assignment of the

• confirmed by HMBC correlations (Figure 3). This fragment was connected to the previously assigned moiety through a HMBC correlation from δH 3.25 to the amide carbonyl (δC 164.9), thus enabling the full chemical structure of ianthelliformisamine G (7) to be assigned. Compounds 6 and 7 are both commercially

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• isomers, two due to the E and Z isomers of the imine group (–N=CH–) and two due to the syn/anti-conformers of the amide bond (–NH-CO–). Experimentally, the E isomer is often more stable and so, predominant. The strong correlation between the NH and CH of the imine observed in 2D 1H-1H NOE experiments for

• the two conformers of hydrazones 3e and 3f (see Supporting Information File 1) is in accordance with the E stereoisomers. Furthermore, another correlation is observed for one conformer involving the NH of the imine on one side and the α-proton and the CH2 of the Cbz of the phenylalanine on the other

• . This correlation is present for one conformer (anti) and not for the other (syn), and this observation is similar for hydrazones 3e and 3f (see Supporting Information File 1). Based on these experimental data we can hypothesize the geometry of the two conformers of hydrazones 3e and 3f is E,syn and E

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

• due to the lack of suitable reference acids in the weakly acidic pKa region in acetonitrile only two reference acids were used. The results are presented in Table 2. We estimate the standard uncertainties of the assigned pKa values of BFC and FIC as 0.15 pKa units. pKa predictions using correlation

• analysis The pKa values of fluorene, indene, cyclopentadiene, 9-phenylfluorene, and diphenylmethane in acetonitrile were estimated by averaging the values obtained from their experimental pKa values in DMSO [5] and three correlation equations: equations 2.1 and 2.2 in Ref. [13] and correlation equation

• obtained from different equations is not good. Therefore, the standard uncertainties of these obtained pKa estimates are high: 2 pKa units for fluorene, indene and 9-phenylfluorene, 3 pKa units for cyclopentadiene (as this acid is very different from the acids used for developing the correlation equations

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• is no obvious correlation between the quantum yields of the photoreactions and substitution pattern of the norbornadiene in this series, except for a rough trend that naphthyl-linked derivatives, in particular the ones substituted in the 2-position, have lower quantum yields than the phenyl-linked

• ones. This lack of correlation may indicate that several different factors and processes contribute to different extent to the course of the photoreaction, for example, steric hindrance and resulting torsion angles between the arene unit and norbornadiene, deactivation of the excited state by

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• configuration of the double bond was confirmed using 1H,1H-NOESY spectroscopy. As shown in Figure 2, a correlation between protons of the allyl moiety and the aryl substituent evidenced their spatial proximity in molecule 1c. The absence of a correlation between allyl and vinyl protons additionally supported