Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• is then attacked by a nucleophile. The use of chiral iodine catalysts is essential for controlling the stereochemistry of the reaction. The specific arrangement of the catalyst influences the orientation of this nucleophilic attack as supported by density functional theory (DFT) calculations. In 2022

• up to 95% within a short time-frame of 10 minutes. Treatment of N-(2-phenylallyl)benzamides with 10 equivalents of BF3·Et2O, iodobenzene, m-CPBA in dichloromethane (DCM) at 0 °C resulted in the formation of the oxazoline product (Scheme 21). DFT calculations indicated several steps in the mechanism

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , with TBAI as a co-catalyst, up to 74% yields (Table 1). The inactivity of porphyrin 18 was attributed to the inaccessibility of the inner core imine due to its planar structure. The mechanism of the epoxide ring-opening reaction was elucidated by DFT calculations, which suggested that the macrocycle

• (Table 5). DFT calculations predicted that the catalytically active species is the adduct of porphyrin and TBACl (18-I), which forms an activated complex (18-II) with the substrate followed by a ring-opening nucleophilic attack of Cl−. The electron-rich nitrogen atom in 18-III further activates

• conditions also supported the generation of the radical anion [67]˙−. Furthermore, the authors used thermodynamic theoretical calculations to investigate catalytic steps, finding that the protonation of [67]˙− to generate [67-H] is thermodynamically favored (free energy of +2.39 kcal mol−1) over its

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• in the absence and presence of N,N-diisopropylethylamine using density functional theory (DFT) calculations (Figure 1). According to the DFT calculations, the free propargyltrichlorosilane (Iprop) can isomerize to allenyltrichlorosilane (Iall) with a prohibitively high barrier of 43.8 kcal/mol

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• . Moreover, owing to the interaction between the narrower rim side of PMα-CD and the amino groups on the axle ends, the [3]rotaxane- or [4]rotaxane-species-contained PMα-CDs directed their narrower rim sides to the axle ends, as confirmed by theoretical calculations, thus indicating that such relatively weak

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• sufficient quality to obtain a solid-state structure of the oxalate host–guest complex [(C2)@L2Zn2]2− so that we utilized DFT calculations to model the expected structure of the host–guest species (Figure 3a). Therefore, we funneled structural information obtained from NMR spectra into our starting geometry

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

• approximately 150° [42][43][44][45]. These data were consistent with DFT calculations (see Supporting Information File 1). The reaction of the amide 1d with n-BuLi resulted in a surprising outcome. In this case, product 9d and only traces of the expected product 10d were received, as indicated by the 19F NMR

• ]. These findings are in alignment with DFT calculations (see Supporting Information File 1) and corroborate data for compounds 9a–d. We further decided to use tert-BuLi in our research, considering its role as a stronger base and simultaneously as a weak nucleophile. We first performed the reaction with 2

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• the Knoevenagel condensation with malononitrile was successfully reported [33]. Theoretical studies Density functional theory (DFT) calculations of two derivatives of compounds 2 and 3, having methoxy groups instead of the longer alkyl chains have been reported in the literature [32], providing

• hindered charge transport. Experimental Computational Density functional theory (DFT) calculations were performed using Gaussian 09 software. Molecular geometries were initially optimised semi-empirically (AM1) and then reoptimised by DFT using the B3LYP method with the 6-311G(d,p) basis set unless stated

• otherwise. The absence of transition states was confirmed by the absence of imaginary frequencies in vibrational frequency calculations. The long side chains were replaced by methyl units to aid the convergence of the geometry optimisations. Crystallography Single crystal X-ray diffraction data for 3b were

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• aryl sulfides 85 from thiols 84 using diaryliodonium salts 16 in basic conditions (Scheme 34). A multitude of thiols and diaryliodonium salts was examined in the reaction under optimized conditions, yielding exceptional yields [88]. To embrace the chemical process, DFT calculations were performed in

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• , short reaction times, and simple operation. According to quantum efficiency calculations, all pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives with excellent emission could serve as potential candidates for optoelectronic conjugate materials. Experimental General

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -β-41a (55%) and E-β-41a (41%) are in accordance with the relative thermodynamic stability of the two geometric isomers. According to DFT calculations, the Z-isomer is slightly energetically favored by 14.88 kJ/mol. The configurations were determined by comparison of chemical shifts of our products

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

• maleimides or N-arylitaconimides. The mechanism of the studied processes was postulated basing on experimental data, HPLC–MS analysis of reaction mixtures, and quantum chemical calculations. Molecular docking results of the obtained imidazo[1,2-a]pyrimidines, when compared with voriconazole, a drug already

• 2 and 3, the minimum energy paths (MEPs) of these processes were calculated. Quantum chemical DFT calculations were performed using the B3LYP/6-311++G(d,p) basis set and taking into account solvation effects using the polarizable continuum model (PCM). Interactions of 1 with N-phenylmaleimide (2a

• ) and N-phenylithaconimide (3a) were considered as model systems (Scheme 4 and Scheme 5). Based on the calculations performed, the existence of thermodynamically favourable interaction pathways between aminoimidazole 1 and N-phenylmaleimide 2a (pathway A1 and A2) was confirmed, in which intermediates 6a

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• ). Further control experiments and DFT calculations show that during the catalytic process, tertiary amine directly participates as a nucleophilic reagent to give the ammonium salt, which then releases dimethylaminium to provide the final product (Scheme 12). Chiral allylic sulfone compounds can be easily

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

• conditions [37][38][39]. When considering asymmetry, it was necessary to include large substituents on the catalyst to induce steric hindrance. These modifications increase the size of the asymmetric catalysts. Thus, the calculations presented in subsection “Asymmetric catalysis” were optimised at the B3LYP

• -D3(BJ)/def2-SVP computational level. Single point energy calculations on the optimised structures were run at the B3LYP-D3(BJ)/def2-TZVP level to obtain more accurate electronic energies. The reported free energies in this section correspond to the sum of the triple-zeta electronic energy and the

• activated CO2 was found to proceed through two transition states. The calculations showed that the breaking of the O–CH(CH3) bond was more kinetically favourable, with a TS 7.6 kcal·mol−1 lower in free energy than the corresponding TS for breaking the O–CH2 bond. The electron-donating nature of the methyl

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• abilities has been verified by mathematical calculations. Keywords: decarbonylation–oxidation; hydroperoxide; 2-hydroxybenzophenone; transition-metal-free; UV-protection; Introduction Benzophenone compounds are ubiquitous in nature, and show biological activities such as anti-inflammatory, antiviral, and

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some

• studies to elucidate the mechanism of the γ-CD hydration. Herewith, by employing a combination of experimental (differential scanning calorimetry/thermogravimetry) and theoretical approaches (density functional theory calculations) we endeavor to shed additional light on the mechanism of the γ-CD

• groups in intramolecular H-bonds is contradictory and confusing – observations suggest no involvement of secondary hydroxy protons in intramolecular H-bonds and strong exposure of OH-6 groups to the solvent [22]. Our calculations reveal (as expected) that the “closed” narrow-rim arrangement is

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• ]. In each structure, the non-hydrogen atoms were refined anisotropically. CIF files (CCDC-2364292–2364296) can be obtained free of charge from the Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/data_request/cif. DFT calculations. DFT calculations for the geometrical optimizations

• NMR spectra of new ion pairs, details for crystal structures, and theoretical calculations. Acknowledgements Theoretical calculations were partially performed at the Research Center for Computational Science, Okazaki, Japan (Projects: 22-IMS-C077, 23-IMS-C069, and 24-IMS-C067). The synchrotron

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

• scarcity and diversity, as they need to cover a vast reaction space [26][27]. However, collecting data relevant to chemical reactions represents a significant challenge. While specific molecular properties can be precisely computed using existing simulation methods like quantum chemical calculations

• – allowing for the generation of extensive data through large-scale simulations – chemical reactions pose a much greater difficulty for accurate simulation. The development of systematic theoretical calculations to model correlations between reaction yields and various substrates and catalysts requires

• theoretical calculations are typically restricted to gas-phase reactions [31]. Despite these challenges, recent advances in quantum chemical methods have shown that theoretical calculations can provide practical guidance for validating experimental results [32]. Thus, we posit that the role of theoretical

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• -cyclization onto the alkene when n = 3, we modelled this reaction using DFT calculations (Scheme 2). Similarly, we concluded that the present reaction commences with activation of the olefin in 3a by the hypervalent iodine species 8, which is generated under the reaction conditions. The activation occurs via

• ring. We have performed DFT calculations to support the proposed change in mechanism and developed superior reaction conditions to effect this transformation. Finally, we have explored the substrate scope of this cyclization. Functional molecules containing a substituted pyrrolidine core. A) Our

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• and nonbonding interactions for the halogen at C4. Finally, density functional theory (DFT) calculations corroborate the preference of talose analogues to adopt a 4C1-like conformation and a natural bonding orbital (NBO) analysis demonstrates the effects of hyperconjugation from C–F antibonding

• ) [24]. The solution and the solid-state conformational analysis were supplemented with DFT calculations to understand key conformational drivers. This study adds more data to the field of nuclear magnetic resonance (NMR) spectroscopy of polyhalogenated molecules. It should be noted that the NMR

• -halides motivated us to use density functional theory (DFT) calculations to understand the preference of talose analogues to adopt 4C1-like conformations. DFT computations were performed using Gaussian 16 revision B.01 [67] with the CAM-B3LYP [68][69][70] functional and the Def2TZVP basis set [71], which

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• of the analogous nucleophilic addition of cyanide was reported by Chen and Qiao [38] in 2023 (Figure 4). The calculations revealed that ΔG profile for the reaction pathway via 76, in which the imine molecule is activated by the direct chiral proton transfer from the COBI ion and then later attacked

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• energies of relevant species either via force field or quantum chemical methods to assess the properties of a reaction such as activation energies or selectivity. Irrespective of the degree of automation, in silico calculations are often less time-sensitive than wet-lab experiments and can be used to

• mechanical calculations is also increasing, such as a data set that considers propargylation reactions catalysed by bipyridine N,N’-dioxide-derived scaffolds, created by Wheeler and co-workers using their AARON toolkit [21][114][115][116]. Similar to experimental data, computational data sets also lead to

• for this reaction class (ee threshold 80%), even though amine-based catalysts demonstrate a higher average ee. Notably, this strategy is not restricted to literature-extracted examples and can also be applied to enantioselectivities calculated via quantum chemical calculations or predictions from an

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• two anthryl moieties (Figure 3b, Supporting Information File 1, Figure S1). DFT calculations for structural optimization revealed that the energy difference between two DAntM radical structures with different spin positions, spin localization at the central sp2 carbon and on the anthryl group, is

• Figure 6a and 6b, respectively. The DAntM radical exhibited a forbidden near-IR (NIR) band centered at 900 nm and relatively intense bands at 580 and 540 nm, whose spectral pattern is similar to the spectrum pattern of the TAntM radical [17]. The result of TD-DFT calculations could reproduce the obtained

• Research Areas (A) (Grant Number JP20H05865, T. K.), and by research grant from The Murata Science Foundation (T. N.). Quantum chemical calculations were performed at the Research Center for Computational Science, Okazaki, Japan (Project: 23-IMS-C212 and 24-IMS-C214). This work was the result of using

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• from the 100% of pure water, additives decreased that value by the percentage of their contribution. Calculations and further details can be found in Supporting Information File 1. Cell-free protein synthesis The CFPS system was prepared and the reactions performed according to Rolf et al. [18] with

• Supporting Information File 75: Calculations of viscosity, macromolecules, inorganic ions, osmolarity and water content for CFPS in Table 1. Supporting Information File 76: Calculations of viscosity for CFPS with water-soluble solvents in Table 2. Supporting Information File 77: Fractional Yield of average

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

• substituents has a lower Ea than DBA with electron-donating substituents. DFT calculations The reaction mechanism was investigated by computational calculations. The reaction mechanism between 5 and benzyl azide was supported by the ωB97X-D/6-31G(d,p) calculations with the CH2Cl2 polarizable continuum model

• previously reported electron-donating hexyloxy substituents. The addition pattern was experimentally investigated by 2D NMR, which was also supported by DFT calculations. The bistriazole product displayed fluorescence in the visible range with a fluorescence quantum yield of 7.0%. Finally, the developed

• recorded on a JASCO FP-8500. All calculations were carried out using the Gaussian 16 program [21]. The DFT calculations were carried out using the long-range and dispersion-corrected ωB97X-D functional [22]. The 6-31G(d,p) basis set was used for H, C, O, and S atoms [23][24]. The solvent effect of CH2Cl2

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• yield is stated. Keto/enol ratio of 3 was determined by 1H NMR spectroscopy. Gram-scale hydrolysis reactions of 1a. Proposed mechanism for formation of β-keto thioesters 2 and β-keto amides 3. Optimization of the reaction conditions. EcoScale calculations and results for the synthesis of 2a and 3a [75