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

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• similar correlation to size, however, our data-driven analysis revealed that the underlying source of the correlation is not just the molecular size, per se, but rather the formation of linear stretches (substructures that are linearly annulated) [6]. Accordingly, the longer the linear stretch, the higher

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• . Furthermore, we employ our model on 1043 pKa-dependent reactions (aldol, Claisen, and Michael) and successfully indicate the reaction sites with a Matthew’s correlation coefficient (MCC) of 0.82. Keywords: C–H pKa values; pKa predictor; Introduction Over the years, the ability to selectively break a C–H

• as steric hindrance and base reactivity, ensuring even more precise predictions for reaction sites. Correlating computed values and experimental pKa values for 695 compounds. r: Pearson correlation coefficient; ρ: Spearman’s rank correlation coefficient; MAE: mean absolute error; RMSE: root mean

• squared error. QM calculations were carried out at the CAM-B3LYP/def2-TZVPPD CPCM(DMSO)//GFN2-xTB ALPB(DMSO) level of theory. ML-predicted pKa values vs QM-computed pKa values of the held-out test set (155 compounds; 789 pKa values). r: Pearson correlation coefficient; ρ: Spearman’s rank correlation

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• different hypervalent iodine reagents for this reaction. To find the correlations between experiments and theoretical calculations, chlorination and bromination of 2-naphthol using PIFA/AlCl3 and PIDA/AlBr3 were carried out. Consequently, we found an excellent correlation between the yield and the energy

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• . ameranicus using UHPLC-HRMS/MS. Finally, we generated a global natural product social (GNPS) network to show the correlation between metabolites from these different plant species (Figure 5) [29]. Cyclopeptides in Ceanothus americanus The GNPS network showed the presence of multiple features from C

• and Leu-β is supported by HMBC correlation between Tyr-C3 (δ 156.3 ppm) and Tyr-C4 (δ120.5 ppm) and NOESY correlation between Tyr4-H (δ 7.01 ppm, 1H) and Leuβ-H (δ 4.80 ppm, 1H). Similar to other characterized cyclopeptide alkaloids, J-coupling constant (Jα-β = 8.0 Hz) supports S-stereochemistry at

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• indicate that the previously identified fingerprint motifs remain valid for KRs in β-modules from actinobacteria, but their reliability diminishes for KRs from other module types or taxonomic origins. Additionally, we have identified several new motifs that exhibit a strong correlation with the

• most of actinobacterial β-module KRs do fall within there). Overall, the motifs having correlation with stereoselectivity are summarized in Table S1 in Supporting Information File 1. Below we provide a detailed guideline for stereochemical prediction of KRs. For non-actinobacterial PKSs

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• -cyclohexenone. This is further supported by the 13C NMR spectrum, which contains two peaks at δ = 38.4 and 47.7 indicating the two types of benzylic carbons. The NMR data of known compound 4ab were also in good correlation with previously reported data [19]. The synthetic practicability of the protocol was

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

• both homolytic and heterolytic bond dissociation energies (BDEs) critical for assessing the chemical stability and functional group transfer capability of cyclic hypervalent halogen compounds using density functional theory (DFT) analysis. A moderate linear correlation was observed between the

• homolytic BDEs across different halogen centers, while a strong linear correlation was noted among the heterolytic BDEs across these centers. Furthermore, we developed a predictive model for both homolytic and heterolytic BDEs of cyclic hypervalent halogen compounds using machine learning algorithms. The

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• -qzvpp for iodine and tellurium and in the gas phase. In our present work using M06-2x/6-311+G(d) with def2-txvpp for iodine and astatine, we observed excellent agreement in the correlation between orbitals used on the halonium center and the C–X–C bond angle, i.e., molecular geometry, from our prior

• consistent with Bent’s rule in which greater p-character is directed toward more electronegative ligands [44]. We also consider a correlation between Vs,max of the halogen-bond donor and ΔG of the halogen bond (Scheme 6c) [45]. Although a modest linear correlation (R2 = 0.90) was observed over all data

• combination of p-character (%) and σ-hole (Vs,max) provided the highest correlation based on linear regression analysis of ΔGDFT vs ΔGcalc, wherein ΔGcalc is obtained from Equation 1 [46]. Our model was developed with normalized parameters of % p-orbital character and Vs,max and therefore a comparison of the

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• their high viscosity, the 4-Br substituted TAAILs 46 and 47 display the lowest conductivities (96 and 62 μS cm−1, respectively). To visualize the correlation between conductivity and viscosity, the conductivity is plotted against the viscosity in Figure 3. The 4-OCF3 substituted TAAIL 52 shows a similar

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

• below. This analysis allows us to understand the correlation between the stability of hedycaryols and the C+···OH distances, as this descriptor presents the difference in stability trends between hedycaryol and germacrene A cations, which is due to the hydroxy group in hedycaryol cations. where ΔΔEHed

• -Ger = ΔEHed − ΔEGer is the difference between corresponding hedycaryol and germacrene A cations (e.g., A and A-OH). The correlation coefficient, R2, is 0.75, indicating a correlation between the energy difference between carbocations and the C+-OH distance in hedycaryol cations. For example, F-OH has

• to repulsive and yellow represents slightly attractive interactions. The bottom two plots are side views of the cations and emphasize the relatively puckered structure of B compared to A. NCI plots for F and H hedycaryol cations. The C+···OH distances (Å) are shown in black. Correlation plot relating

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• determined by the correlation of their optical rotations with that of the previously reported aryl-lactam 4bb [23], and its deprotected analog [24], as well as with the intermediates 5b, 5a, and 6 in the (R)-rolipram (5b) and (R)-baclofen hydrochloride (6) [25] syntheses. Assignment of the stereochemistry of

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• helpful to have this information easily accessible as Privateer cannot calculate the real space correlation coefficient without experimental data; therefore, programmatic access to further validation metrics could be streamlined, knowing the information is not present. Also at the top level of the

• model of the sugar. Also in the first section of the visual validation report is a plot of the B-factor (temperature factor) versus the real space correlation coefficient (RSCC) (Figure 2). A well-refined, well-built model would be expected to have a B-factor that increases somewhat linearly as the RSCC

• conformational landscape of pyranose sugars. A well-modelled ᴅ-sugar would be expected to be in the lowest-energy conformation and have a theta angle close to 0° and would be indicated by a blue point; deviations from the ideal conformation are highlighted with a red cross. Right: Real space correlation

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• analyzed chemical shifts δ are referenced to the residual solvent signals of the deuterated solvents CDCl3 (δ = 7.26 ppm/77.16 ppm). Multiplicities due to spin–spin correlation are reported as follows: s = singlet, d = doublet, dd = double doublet, m = multiplet; they are further described by their

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• synthetic intermediate of 2 to spiroviolene. By taking advantage of the DFT transition state analysis of the hydroboration reaction of a key intermediate, as well as NOE correlation analysis of the resultant product, Snyder and co-workers have reassigned the right structure of spiroviolene to 1. However

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• ppm in 14. The methine had a correlation to a resonance at δC 55.1 ppm in the 2D HSQC spectra consistent with an attached chloride. In the 1H NMR spectra for the hemiacetals 12a,c–f, an upfield shift for the anomeric centre of ≈1.1 ppm was observed relative to the chlorides. There was also evidence of

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• differences in 13C NMR (ΔδC = 3.3) (Figures S19–S25, Supporting Information File 1) [43]. Moreover, the key correlation observed between H5 and H7 in the ROESY spectrum provides additional support for the β-configuration of this hydroxy group (Figure S26 and Table S7 in Supporting Information File 1). These

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• thermally treated alumina and SOCl2 (2 equiv) as an ideal HCl precursor, affording the product 62 in a 94% yield with 100% conversion in only 18 minutes of reaction time (Table 4, entry 3). During their investigations, they discovered a correlation between the efficiency of the hydrochlorination reaction

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• except for 4ClDPAIPN which afforded 10% of yield of 4a (Table 2, entries 6–10). No correlation between the different redox potentials of the photocatalysts and the yield of the reaction could be established. Ru(bpy)3Cl2·6H2O was selected as the optimal catalyst since it afforded the highest yield and

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• the DFT calculation realized by the PWscf code of Quantum ESPRESSO [30][31][32], the DFT-D3 correlation [33] together with PBEsol functional [34] for the exchange-correlation functional described van der Waals interaction between graphene and pyrene fragment in PASE. Ultrasoft pseudopotentials [35

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• carbon, and one methyl carbon. A spin system H-6 (δH 6.85)/H-7 (δH 7.33) with an ortho-coupling constant (8.5 Hz) was observed using homonuclear correlation spectrometry (COSY). The heteronuclear multiple bond correlation (HMBC) cross-peaks from H-6 to C-2 (δC 112.4) and C-4 (δC 145.2), and from H-7 to C

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• correlation of faster rate with more electron-withdrawing ligand. Experiments with other substrates display consistent results (further discussion below, Table 6, catalyst 4a reacts faster than 4c in the reaction of carbamate 1b → 3b). Solvent effect For a screen of solvent effect on the rate of 1a

• (Table 2, entries 1 and 2; 4–22-fold increase in rate compared to CD2Cl2). We were unable to find any clear correlation between rate and a variety of solvent parameters; the success of mixed solvents suggests many factors are at play. Throughout our studies, we used CH2Cl2 and CD2Cl2 interchangeably

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• the HMBC correlation from H-14 to C-8, as well as the molecular formula combined with chemical shifts (δC 35.9, CH2-14, and δC 45.8, CH-8) [12]. Furthermore, HMBC correlations from the protons of methoxy to C-2 attached the methoxy group to C-2. The relative configuration of compound 1 was determined

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• prostate cancer. The same apoptotic function can be observed in colon and pancreatic cancer, since BIMs (specifically DIM-C-pPhOCH3 (5)) can act as a Nur77 (Nuclear Receptor 4A1) antagonist, which modulates the life cycle of cells [6]. The correlation between lower lung cancer risk and the consumption of

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

• angles for N,N'-dimethylindigo in the E- and Z-forms were 30.7° and 27.4°, respectively. Importantly, the twisting angle of the E-isomer is not always smaller than the one of the Z-isomer. Interestingly, no correlation between the positions of the absorption maxima of both E- and Z-isomers of the dyes 9a