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

• Shuang Yang Xinqiang Fang State Key Laboratory of Structural Chemistry, and Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, Fuzhou

• substitution has emerged as a new and robust approach to achieve formal allylic substitution using stabilized nucleophiles. The copper acetylide-bonded allylic cation with copper vinyl allenylidene species as its resonance structure is key for the process, which can achieve the outer-sphere attack of

• structure precludes stable copper-carbonyl interaction, favoring attack from a less hindered site. Later, Qi and Xu et al. [75] achieved highly enantioselective copper-catalyzed [4 + 1] cyclization of yne-allylic esters and cyclic 1,3-dicarbonyls, achieving remote stereoselective control through copper

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• was taken into the ESR tube and ESR spectra were recorded at room temperature. (a) Chemical structure and schematic illustration of the charge-separated state of a triad molecule and (b) control of the membrane potential by the illuminated molecule with a favourable arrangement. (c) Strategy of the

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• was studied by UV–vis and fluorescence spectroscopy. Keywords: cross-coupling; cyclization; heterocycles; palladium; Introduction Nucleobases contain the coded information and give DNA and RNA their typical structure. As a nucleobase, uracil is involved in numerous vital processes and is therefore a

• with a certain fine-structure for compounds 5a, 5g, and 5i and structure-less absorption features for compounds 5d, 5f, and 5h containing electron-donating functional groups are observed. In addition, the presence of strongly electron-donating N,N-dimethylamino groups leads to increased extinction

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• RdRp inhibitor, and their evaluation in an in vitro polymerase assay, targeting SARS-CoV-2 [17]. The synthesis of the new molecules involved three modifications of the HeE1-2Tyr inhibitor, which included changing the core structure from a benzothiazole to a benzoxazole unit and simplifying it to

• , focusing on heteroaromatic structures with known pharmacological profiles [21]. They highlighted that changes in the phenyl and heteroaryl ring systems often stemmed from structure–activity relationship (SAR) exploration, where bioisosteric modifications of the original phenyl hits were prevalent. They

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluoroenynes via Suzuki–Miyaura and Sonogashira cross-coupling reactions using novel multihalogenated fluorovinyl ethers, which are easily prepared from the reaction between phenols and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane). These reactions make use of the unique structure of multihalogenated

• -chloro-1,1,1-trifluoroethane (halothane) in good yields (Scheme 1D) [42]. Compound 1 has a unique structure possessing three types of halogen atoms, namely bromine, chlorine, and fluorine, and it would be expected to afford multisubstituted fluoroalkenes by installing various substituents to bromine or

• Sonogashira cross-coupling to exploit the unique structure of multihalogenated fluorovinyl ethers 1 for the synthesis of many kinds of fluoroalkenes 2 and fluoroenynes 3 in moderate to high yields. The synthesized alkenes 2 still possess reactive chlorine atoms and phenoxy groups. Thus, new multisubstituted

Photoluminescence color-tuning with polymer-dispersed fluorescent films containing two fluorinated diphenylacetylene-type fluorophores

• Kazuki Kobayashi,
• Shigeyuki Yamada,
• Motohiro Yasui and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2682–2690, doi:10.3762/bjoc.20.225

• diphenylacetylene structure as the π-conjugated core. As a part of our research projects, we have begun to explore diphenylacetylene-based luminescent molecules despite diphenylacetylene not exhibiting fluorescence at room temperature because it undergoes a πσ* excited state that rapidly forms a trans-bend

• structure (Figure 1a) [14][15][16]. Our extensive efforts have revealed that introducing electron-donating alkoxy and electron-withdrawing cyano groups at both ends of the diphenylacetylene scaffold slows the internal conversion to the πσ* excited state. Further incorporating four fluoro substituents in the

• PL lifetime was measured using a Quantaurus-Tau C11367-34 fluorescence lifetime spectrometer (Hamamatsu Photonics, Japan). (a) Reported photophysics of diphenylacetylene after photoexcitation. (b) Our molecular design to suppress internal conversion. Relationship between the molecular structure of

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

• remarkable 96%ee yielded by the catalyst. Schematic representation of an (A) 2D and a (B) 3D volcano plot. The abbreviation “cat.” stands for catalyst. (A) Structure of PO annotated with the C–O bond distances and electron densities at the BCPs. BCPs are indicated by green spheres and the ring critical point

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

• developed. NMR studies confirmed the role of in-situ-generated hydroperoxide in the conversion. The protocol was applied to a diverse range of substrates to access the target products in good to excellent yields. A structure–activity study for the 5-substituted-2-hydroxybenzophenones towards UV-protection

• -absorbing as well as photo-antioxidant properties via an intramolecular hydrogen transfer [5]. The structure–activity relationship between the substituents of 2-hydroxybenzophenones and their UV-absorption properties has been reported previously [6]. It was concluded that the ability to absorb UV light and

• UV-protector, or its metabolites, have been associated with estrogenic activities [7]. A further structure–activity relationship study revealed that a 5-substitution decreases estrogenic activity. Similar results were obtained in another study where 2-hydroxy-5-methylbenzophenone was found to exhibit

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ) were observed with similar mass spectra. The amount of secretion available and the complex mixture did not allow for the isolation of enough material for NMR analysis. Therefore, for the structure elucidation of these unknown compounds, we used different analytical methods, including GC–MS, GC–IR, and

• GC–HRMS. Additional chemical derivatization of the extracts and final synthesis of the proposed structure candidates led to the structures of compounds A–F. Unknown compounds A–F Compounds A–F showed closely related mass spectra (Figure 2) and mostly occurred as pairs of diastereomers, labeled, e.g

• ., B and B’ here. The molecular ion and one of the fragment ions both increased by 14 Da, respectively, within the series. This suggests that A–F have the same core structure, but different chain lengths. Although the mass spectra showed small ions m/z 60 and 73 characteristic for aliphatic carboxylic

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

• energetically more favorable than the “open” configuration (by 22.3 kcal mol−1), which is why the “head–tail” structure was used in subsequent evaluations. It should be noted that for the two conformers modelled, the “closed” one has the typical truncated cone shape whereas the open one is more like a cylinder

• the cavity walls resulted in one of the a–e variants. The enthalpies of the single water molecule constructs (γ-CD–H2O) are calculated relative to structure a, although structure d is energetically preferred. In structure d, the water molecule is completely outside the CD cavity and is bound to OH-2

• guest water molecule at the expense of destroying one hydrogen bond from the initial γ-CD structure. It should be noted that coordination of water to the wide rim (construct d) creates two new H-bonds between the CD host and the guest water molecule and one H-bond between secondary OH-groups of γ-CD

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• gives rise to difficulties in understanding and predicting gel structure and properties [2]. In order to understand the supramolecular structure, a robust characterisation regime is required. A comprehensive work edited by Weiss and Térech discussed in detail the plethora of chemical systems

• change in the self-assembly, meaning a true representation of the supramolecular material may not be investigated which is rarely confirmed when applied to the characterisation of such systems. To identify such changes in structure, other characterisation techniques that probe the structures without the

• ]. The work by Alakpa et al. highlights how important it is to consider how one assesses the impact of co-assembly on a molecular system [20]. AFM suggested that the addition of the surfactant-like Fmoc-serine (Fmoc-S) to the fibrous Fmoc-diphenylalanine (Fmoc-FF) did not impact the structure of the Fmoc

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• , including drugs and alkaloids [8]. Several drugs are known to contain the 2-pyridone structure, such as the cardiotonic drugs milrinone (Figure 1c) and amrinone (Figure 1d) [9][10], as well as the antibiotic pilicide (Figure 1e) [11][12]. As described in [13] during preliminary experiments, it was

• ][19][20]. The catalytic activity of metallophthalocyanines originates from their planar, cyclic structure with a developed π-conjugation system. This makes the fifth and sixth coordination sites of the central metal ion available for coordination with the reactant molecules of the catalytic reaction

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• scaffolds for bioactive molecules. Thus, it appeared interesting to explore novel molecules with extended aromatic units around this basic quinazoline core and our first choice was N-arylbenzo[h]quinazoline-2-amines with the general structure C as indicated in Figure 1. Very limited studies have been

• devoted to the synthesis of this core structure and, to the best of our knowledge, only one molecule of this type was obtained in low yield as a secondary product during studies on the use of the Friedländer annulation reaction starting from naphthylamines [12]. Therefore, the goal of this paper is to

• should allow us to introduce the molecular diversity on the anilino moiety in the last step through a palladium-catalyzed reaction (Scheme 1). Therefore, we prepared first the core structure 3 in two steps from the commercially available fluoronaphthalene 1. Metallation, followed by trapping with DMF

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• formation of various unidentified byproducts. The obtained tetronic acids 4 are solid crystalline compounds, whose structure was proved by 1H, 13C NMR spectroscopy and high-resolution mass spectrometry. The 1H NMR spectra of the synthesized products contain characteristic signals of protons of the methyl

• fragment in the region δ = 2.5–2.4 ppm and methylene unit at δ = 2.7–2.5 ppm. The remaining signals are also in good agreement with the presented structure. Besides that, compound 4 has been analyzed using X-ray diffraction (Figure 1). It is important to emphasize that based on X-ray data the structure of

• ]+ calcld for C30H32ClN2O4, 519.2045; found, 519.2051. The X-ray crystal structure of compound 4a (CCDC 2352876). The X-ray crystal structure of compound 7 (CCDC 2352878). Synthesis of tetronic acid derivatives. Synthesis of amide derivatives 3. Synthesis of target tetronic acids 4a. aReaction conditions

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

• ] formed a charge-by-charge assembled structure, with alternate stacking of TATA+ and PCCp− through iπ–iπ interactions in the crystal state [20][21]. Charge-by-charge stacking assemblies of 1a+ and porphyrin-based π-electronic anions showed the crystal-state PET between proximally located anions and

• 524 nm was mainly derived from HOMO−1/HOMO-to-LUMO transition (HOMO: highest occupied molecular orbital, LUMO: lowest unoccupied molecular orbital), as revealed by the time-dependent density functional theory (TDDFT) calculation of the optimized structure of 2+ at the B3LYP/6-31+G(d,p) level of theory

• deviations of 0.014–0.071 Å for the 22 core atoms. 2,6-Dimethylphenyl units were orthogonally arranged with dihedral angles of 81.0°–89.9°, which are similar to those of N-phenyl-substituted 1b+ [26]. In the packing structure, the 2+-Cl− units were aligned in a columnar structure with an interplane distance

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

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

• recognition to parse molecular structures and convert them into textual representations. Qian et al. [73][74] demonstrated that this task of optical chemical structure recognition (OCSR) [75] can be handled with a model that combines an image encoder and a molecular graph decoder. Despite the promising

• ][116][117], regioselectivity, and site-selectivity [16][17][118][119][120]. However, this approach is also computationally demanding and requires a good initial guess of the TS structure. Moreover, it may face difficulties in simulating some classes of reactions and large-size molecules [121], and the

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• translated to the formation of other macrocycles as long as they share a similar reaction mechanism. (a) Control experiment testing deiodination of 2-iodoresorcinol. (b) Molecular crystal structure of chlorinated resorcin[4]arenes 1h and 1i, and carboxylic acid-containing 1s at 100 K. Thermal ellipsoids are

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

• tetrahydrooxazepine) as well as DEPT, HSQC, and HMBC data for 7a support the assignment of the pyrrolidine structure. The next stage of the project was to improve the yield of the reaction. We initiated our study by using our initially developed conditions using 20 mol % 2-iodoanisole and found that the reaction

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

• are nearly degenerate. In solution, the picture is much clearer: the 4C1 structure is always lower in enthalpy and Gibbs free energy, which corresponds with the experimental measurements. One can see that the gap between the two structures tends to decrease as the halogen becomes larger (the minor

• orbitals to C–F (or C–X) antibonding orbitals that are aligned with one another. The principal difference between the two structures is that in the 1C4 structure there are two such interactions whereas in the 4C1 structure there are three. One can see that in the 4C1 structure the C5–H5 bond will donate to

• the antibonding orbital of the C4–X4 bond, and the C3–H3 bond will donate to the antibonding orbitals of the C4–X4 and the C2–F2 bonds. In the 1C4 structure, the C4–H4 and C2–H2 bonds will both donate to the antibonding orbital of the C3–F3 bond. These effects can be shown with an NBO analysis: the

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• of the reductive elimination very slow, the intermediary Cu(III) species safely existed until the addition of D2O. Because the significant overlap of NMR peaks was observed due to the quite similar structure of 11a and 11a-D, quantitative analysis of the deuterium content of 11a-D was not possible

• , 2856, 1720, 1469, 1291, 1176, 1146, 899, 841, 719, 643 cm−1; HRMS–FAB+ (m/z): [M + H]+ calcd for C14H26F3O2, 283.1879; found, 283.1893. Crystallographic structure of the epoxy ring-opening products by PhCH(NH2)Me (3bd) and PhCH2SH (4ba). Crystallographic structure of anti,syn-8a. A part of 13C NMR

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

• the efficient mixing of organic phases (cyclopentadiene, 1,2-dichloroethane, and MeBu3NCl) and aqueous phases (30% NaOH) and optimized it by the use of a simple homemade “PTFE Raschig ring static mixer” (RRSM). The RRSM is simple in structure, easy to fabricate, inexpensive for many flow reaction

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• organocatalysis, previously only iodine(I)-based Lewis acids had been applied. However, after this study, the application of DAI salts as XB donors gained increasing interest and was investigated by several groups [11]. In the last years, important information about structure–activity relationships was also

• it with our known iodonium species in the activation of Au(I)–Cl bonds. Results and Discussion As immediate precursor to the target structure 7Z, the literature-known isoxazole 10 was synthesized via a Cu(I)-catalyzed cycloaddition between (2-iodophenyl)acetylene (8) and benzyl nitrile oxide, which

• ) Å, 84% of Σr, and C1–I1···Br1 = 176.08(9)°]. The bond distances indicate that the hydrogen bond is noticeably weaker than the two XBs and thus constitutes merely an assisting interaction. The XB interactions in this crystal structure were compared to the ones in the literature-known co-crystal of

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• ), antituberculosis agents [13], as well as in drugs against arrhythmia (nesapidil) or muscular dystrophy (ataluren) [21]. The 1,3,4- and 1,2,4-oxadiazoles are the most promising from the point of view of bioactivity among the four isomers of oxadiazole. The presence of a 1,3,4-oxadiazole ring in the structure of

• possibility of alkylation of the nitrogen atom in the heterocycle cannot be excluded. This alternative pathway is similar to the previously described interaction of the aforementioned catechol with 3,5-dimethylpyrazole or benzimidazole [55]. A study of the structure, electrochemical properties, anti

• of complexes 5 and 8 do not contain any solvent molecules, while the unit cell of crystals 6·0.5CH3CN contains one acetonitrile molecule per two catechol molecules. The nitro-substituted pyridine group in 5 is disordered in two positions. The X-ray structure of catechol 5 is shown in Figure 1, and

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

• the asymmetric addition of organoboron reagents to imines (Scheme 3). An intermolecular hydrogen bonding between a non-rigid organocatalyst and a non-rigid substrate was shown to play a key role in assembling a configurationally stable transition structure. As a result, this approach unveiled the

• . Optimisation of the catalysts structure revealed that the 3-phenanthrylpyrrolidine derivative provided superior yields and selectivities. Notably, the isomeric 9-phenanthrylpyrrolidines remained selective but gave noticeably lower yields. The methyl group, geminal to the phenanthryl, plays an important part in

• , in the COBI–imine complex 74 it appears at 8.41 ppm, while in the imine TfOH salt 75 it shows at 9.24 ppm. This detailed NMR investigation sparked further interest in the structure of the transition state of this reaction. An analysis of the potential energy profiles of the two hypothetical pathways