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

• diaryliodonium triflates such as 8 and 9 [13]. They studied a model reaction with 2-aminopyridine (1), p-tolualdehyde (10) and cyclohexyl isocyanide (11) both experimentally (by binding and kinetic studies) and theoretically (by density functional theory (DFT) calculations) (Scheme 5). Catalyst 8 was found to be

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• (1–3 % spectroscopic yield) when BF3·OEt2 was added to the reaction mixture. X-ray crystallography and DFT calculations The solid-state structure of difluoroiodane 6 is shown in Figure 2 and displays the expected square pyramidal geometry around the iodine atom, with only minor distortion (τ5 = 0.191

• Supporting Information File 1). DFT calculations were carried out to gain further insight into the structures of iodine(V) fluorides 21 and 22 whose X-ray structures could not be obtained, and hypothetical iodine(V) amides 7a and 7b which could not be made. Comparisons were made with iodine(V) compounds 6

• . The only major difference between the bicyclic and monocyclic iodine(V) fluorides is the much smaller O–I–O bond angle (161.4(2) °) in difluoroiodane 6 compared to the F’–I–O bond angle (167.9(2) ° in 20) in the monocyclic iodanes 20–22. In fact, DFT calculations predicted that hypothetical

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• been achieved as well. Other efforts have demonstrated that anthracene diimides (ADIs) can be tuned to achieve decent electron mobilities in electronic settings [13][14]. Although there have been calculations conducted that suggest 6-membered cyclic imides are more compelling than 5-membered cyclic

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• yields (82–85%) (Scheme 28). The authors proposed a free radical mechanism facilitated by hydrogen peroxide, generating a primary radical at the terminal nitrogen atom -CO-HN• which then adds to the carbon atom of the imino group. The reaction mechanism was substantiated by theoretical calculations

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

• methods are evaluated as single-point calculations or optimization and frequency calculations. For comprehensive details, refer to Supporting Information File 1, section “Benchmark study - computational methods”. Hereafter, we check the geometries for imaginary frequencies and use the total thermal energy

• Finkelmann et al. [30][31] and Ree et al. [14], we utilize the automated approach to compute CM5 atomic charges from semiempirical tight-binding (GFN1-xTB [37]) calculations. We modify the workflow to enhance the accuracy of the computed CM5 atomic charges. Instead of generating a single random conformer, we

• 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

• reported by our group, was elucidated via quantum chemical calculations using density functional theory. The chlorination mechanism using PIFA and AlCl3 demonstrated a better experimental and theoretical yield compared to using PIDA. Additionally, the lowest-energy chlorinating species was characterized by

• , and transition-state structures were optimized by density functional theory (DFT) calculations employing the software Gaussian 16 [34]. Although the B3LYP functional could be suitable for these calculations, e.g., for tracing reaction pathways, nitrations, halogenations, or FC acylations in solution

• , the 6-31G(d) basis set was used for the other atoms (i.e., H, C, O, F, Al, etc.). Geometry optimizations were carried out without any symmetry constraints, and the stationary points were characterized by analytical frequency calculations, i.e., energy minima (reactants, intermediates, and products

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• the impact of gauche and anomeric effects on the conformer stabilities of different stereo- and regioisomers. Initially, we conducted a benchmark assessment comparing the optimal density functional theory method with coupled cluster with single and double excitations (CCSD) calculations and

• . In this study, initially, the conformational equilibrium of 3-fluoropyrrolidine and the corresponding cation were analyzed to establish a benchmark for selecting an appropriate theory level for subsequent calculations. Then, the different isomers of the 1,2- or 1,3-difluorinated pyrrolidines were

• (Table 1). Consequently, the B3LYP-D3BJ/6-311++G** level was selected for further calculations involving the difluorinated pyrrolidines shown in Figure 4. From the pool of 24 potential conformational, configurational, and constitutional isomers of the difluorinated pyrrolidines (i.e., 1–24), two pairs

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

• DFT calculations for predicting key properties of organic molecules such as BDE, nucleophilicity, and electrophilicity [48][49][50][51][52][53][54][55][56][57][58][59][60]. Recently, applications of the Elastic Net model with Avalon fingerprints [55] and the deployment of artificial neural network

• iodine [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76] and the computational database of organic species by Paton and co-workers [77], geometry optimizations and single point energy calculations for homolytic BDEs are both performed using M06-2X/def2-TZVPP [78][79][80] in the gas phase

• at 298.15 K by Gaussian 16 [81]. Frequency calculations confirmed that optimized structures are minima (no imaginary frequency). The accuracy of computational BDEs of halides using M06-2X/def2-TZVPP is also evaluated and compared to experimental BDEs, demonstrating the reliability of the method (see

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

• the theoretical framework describing the structure, bonding, and reactivity of diarylhalonium compounds [27]. Although some relativistic effects of astatine may not be sufficiently incorporated in calculations [28], others have shown in theoretical and limited experimental studies that astatine does

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• DFT calculations in Supporting Information File 1). Therefore, it was proven that the 2,3-oxazolidinone protecting group was powerful enough to prevent intramolecular glycosylation of monomer 14. However, it did not prevent intramolecular glycosylation of the linear disaccharide and promote the

• monomers 6 with a 2-PhthN group. Electrochemical polyglycosylation of monomers 17 with a 2-azido group. Supporting Information Supporting Information File 18: Synthetic details, DFT calculations, and compound characterization data. Acknowledgements We thank Koganei Corporation (Tokyo, Japan) for donation

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

• -eunicellane skeletons, respectively. Although the structures of these diterpenes only differed in their configuration at a single position, C1, they displayed distinct chemical and thermal reactivities. Here, we used a combination of quantum chemical calculations and chemical transformations to probe their

• rearrangement; DFT calculations; diterpene; electrophilic cyclization; eunicellane; Introduction The eunicellane diterpenoids are a family of nearly 400 natural products that present a conserved 6/10-bicyclic hydrocarbon framework [1][2][3]. Mostly known from soft corals [2], but with a growing number of

• chemically-induced cationic cyclization mechanisms, we performed quantum chemical calculations [mPW1PW91/6–31+G(d/p)/SMD(chloroform)] [13][14][15][16][17][18][19][20] to obtain the relative free energies of the cationic intermediates and transition states that interconvert them, as well as the relative free

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• (Figure 3, path I) [132]. Similarly, Tomberg et al., note that in such reactions, amide is formed rapidly by opening the maleic anhydride ring first, followed by a slower cyclization [133]. On the other hand, according to the results of some DFT calculations, Naguib et al., state that [4 + 2

• study indicates that the retro-IMDAF reaction does not occur under the reaction conditions developed. As seen in Figure 4b, the different sigma bond lengths formed in the exo transition state (calculations which were performed in Gaussian 16 Rev B.01 (Gaussian, Inc., Wallingford, CT, USA)) [135

• IMDAF reaction. IRC calculations of a) endo-, b) exo-transition structures and products for compound 2a (semi-empirical method, PM6) [136]. Synthesis of epoxyisoindole-7-carboxylic acids 2a–m and 2n–p. Possible side reactions of unsaturated fatty acids with maleic anhydride. Equilibrium of 2n–p with

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• diameter range. The diameter selectivity is supported by the theoretical calculations with the GFN2-xTB method, indicating that the most preferred SWNT diameter for the square Cu-nanobrackets is 1.04 nm. Keywords: complexation; diameter; extraction; interlock; nanobracket; single-walled carbon nanotubes

• summarized in a graphene map (Figure 5c). This shows that Cu-nanobrackets 1b preferentially recognize larger diameters with wider range (0.94–1.10 nm) than 1a (0.90–0.92 nm) due to the larger cavity with more flexibility of 1b than 1a. Theoretical calculations To interpret the diameter selectivity, the

• diameters ranging from 0.94 to 1.10 nm among ≈20 kinds of SWNTs from 0.76 to 1.20 nm in their diameters. The most preferable SWNTs for 1b are found to be 1.04 nm in diameter by theoretical calculations, supporting the experimental results. Experimental Materials and instruments Reagents were purchased from

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

• start at 0 V. Structures of the imidazolium cations obtained by DFT calculations (B3LYP/6-311++G (d,p)). The electrostatic potentials are indicated by color (blue: positive; red: negative). Overview of the synthesis of compounds 1–63. Thermal decomposition point at 5% mass loss in °C for NTf2− TAAILs 37

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• different fine structures. However, TD-DFT calculations using the long-range correlated CAM-B3LYP/6-311G(d,p) level of theory reveal that the lowest energy band for all three derivatives 6a, 9a and 12a originate mainly from a HOMO→LUMO transition with some admixture of HOMO−1→LUMO+1 and HOMO−1→LUMO

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• Supporting Information File 72: General information, detailed experimental procedures, additional spectroscopic data, quantum-mechanical calculations, photostability and photoisomerization experiments. Funding We acknowledge generous financial support from the JGU Mainz and the German Federal Environmental

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• calculations suggest that the highest occupied molecular orbital of methyl anthranilate was deeply buried, which suppressed the oxidative polymerization pathway. Due to solvent oxidation, oxamide formation was also noticed to a considerable extent. This study provides that utmost care must be exercised while

• with arylamines follows a complex reaction pathway, leading to a mixture of compounds. We established the possible reaction pathways using 77Se NMR spectroscopy and single-crystal X-ray crystallographic studies. Density functional theory (DFT) calculations were carried out to understand the relative

• interactions are rarely reported and currently gaining interest [59]. Computational studies To comprehend the role of electron-donating and -withdrawing groups in arylamine oxidation using SeO2 as oxidant, DFT calculations were carried out on the arylamines and SeO2 using Gaussian 16 [60]. The molecular

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

• reaction trajectory towards this pathway and make sure that it stays along this pathway and does not rearrange to a similar, more stable carbocation. Here, using density functional theory (DFT) calculations, we provide a rationale for the relative stability of the intermediate carbocations formed from

• and hedycaryol were prepared from their corresponding SMILES string using the RDKit library [30]. Electronic structure calculations on these carbocations were performed using the hybrid DFT functional M06-2X [31] and with the range-separated hybrid meta-GGA functional ωB97M-V [32] with the 6-31+G(d,p

• ) basis set [33]. Additionally, to check the reliability of the energy calculations single point calculations were also performed with the larger def2-TZVPP [34] basis set for both functionals and to account for intramolecular non-covalent interactions, D3 dispersion corrections were added to the M06-2X

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• silirane (silacyclopropane) derivative of fullerenes. Electrochemical measurements confirmed that the redox potentials of 3 are shifted cathodically compared to those of the parent mono-adduct 2. Density functional theory (DFT) calculations provided the basis for the electronic properties of compound 3

• -silylene adduct 3 of C60 based on spectroscopic measurements, X-ray crystallography, electrochemical analyses, and theoretical calculations. Results and Discussion Synthesis of bis-silylene adduct 3 The synthesis of the silylene adduct was conducted using a modified literature procedure [15]. A degassed

• . These results confirm that the two addends in 3 are both silirane structures, which represents the first example of a crystallographic analysis of silirane derivatives of fullerenes. Theoretical calculations Hirsch and co-workers reported the bis-functionalization of C60 using the Bingel–Hirsch, the

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• polyethyleneimine derivatives by coupling ethylene glycol and ethylenediamine using manganese-pincer catalyst Mn1 (1 mol %), t-BuOK (10 mol %) in toluene at 150 °C (Scheme 21) [48]. The mechanistic investigation based on the experimental and DFT calculations suggested a BH pathway. First, dehydrogenation of the

• amount of t-BuOK (20 mol %) in t-AmOH at 135 °C for 24 h allowed for the investigation of several alkyl and aryl ketones with amines and vicinal diols yielding good to excellent yields of the desired pyrroles (Scheme 70) with water and hydrogen gas being the only byproducts. DFT calculations suggested

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• Qian Liu Glen P. Miller Department of Chemistry, University of New Hampshire, 23 Academic Way, Durham, New Hampshire 03864-3598, USA 10.3762/bjoc.20.97 Abstract DFT calculations demonstrate that an isoacenofuran of any size possesses a smaller HOMO–LUMO gap than the corresponding acene bearing an

• . However, calculations indicate that the center ring of pentacene and other acenes is the most aromatic [2] and therefore resonance form P3 of Figure 1 is most significant. By contrast, isotetracenofuran and other isoacenofurans can only be drawn in one neutral, closed-shell resonance form in which only

• isopentacenofuran series (compounds 17–20). They possess HOMO–LUMO gaps between 1.25 and 1.36 eV, well below the 1.77 eV value calculated for hexacene. These Spartan ’20 [8] calculations confirm our expectation of a more highly delocalized π-system in any isoacenofuran (Figure 2) compared to the corresponding acene

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

• barriers were accounted using the DLPNO-CCSD(T) and (8,8)-CASPT2 methods, respectively. The photophysical properties including the absorption onset, excitation wavelengths, and the absorption intensities were extensively investigated with the time-dependent calculations. The result provides information on

• is associated with dissociation of the photoproduct. To validate the interconnection of the TS with the metastable photoisomer and the expected degradation product, IRC calculations were performed. The IRC calculations confirm that the obtained TS interlinks the metastable photoproduct with an

• undesired byproduct (Figure 3). Calculations reveal that the barrier for thermal dissociation of the photoproduct type-Id (209.43 kJ/mol) is significantly larger than the TBR barrier accounted for all the studied photoswitches. Nevertheless, the results reflect the propensity of the type-Id system to yield

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• illustrated in Figures S37–S41 (Supporting Information File 1). This serves as good evidence that the synthesized compounds exhibit no signs of aggregation in DMSO within the assessed concentration range (i.e., 2.5–45 μM). Electronic structure calculations Gas-phase computational investigations were conducted

• to estimate energies of the frontier molecular orbitals (FMOs), specifically the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), for DCPQs 1a–7a as well as 1b–7b. The density functional theory (DFT) calculations were performed using the B3LYP/6-31+G

• ). Cyclic voltammetric measurements of DCPQs, specifically 4a and 6a, and DPQDs 4b and 6b, support the overall trends observed through the electronic structure calculations. X-ray crystallography Single crystal X-ray diffraction data could be obtained for 2b, 5b, and 6b. Figure 6 illustrates the single

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• tridentate chiral ligands: PyBOX [15] and PyBidine [16]. Additionally, we explored further modifications by substituting the pyridine moiety with an imidazole ring in ligand III (Figure 1), motivated by DFT calculations (see Supporting Information File 1, part S4) which confirmed that imidazole has a similar

• catalysed by copper(II) complex of ligand IV. Asymmetric aldol reactions of various aldehydes with ketones catalysed by compound IV. Supporting Information Supporting Information File 62: General information and experimental data of prepared compounds, copies of 1H and 13C NMR spectra and DFT calculations

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• of this straightforward and selective reaction for Li+@C60. Results and Discussion We began by performing density functional theory (DFT) calculations to screen the substrates with suitable HOMO levels for the thermal [2 + 2] cycloaddition with Li+@C60. The structures of several kinds of possible

• a HOMO level of −6.08 eV or higher, such as styrene derivatives 1, 2, and 3. Based on the results of theoretical calculations, styrene derivatives 1, 2, and 3 were selected as the reactants for the thermal [2 + 2] cycloaddition with Li+@C60. For comparison, we also investigated the reaction of