Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• fused structure toward a phenanthroline diamide (Phen-2,9-diamide) [23] can be achieved by employing a palladium-catalyzed intramolecular C–H arylation [24][25][26][27][28]. One of the thus obtained products exhibited a remarkable extraction performance for a lanthanide ion, in which a metal-specific

• arylation precursors 1a–c. Palladium-catalyzed intramolecular direct arylation for synthesizing 8a and 8b and the X-ray crystallographic structure of 8a. Studies on the reaction conditions for 2a from 1a. Pd-catalyzed C–H arylation of heteroarenes. Supporting Information Accession code CCDC 2227450

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• materials [1][2]. Due to their importance, different synthetic routes involving stoichiometric and catalytic approaches have been developed. The α,β-unsaturated imines, also known as conjugated imines or 1-azadienes, are useful precursors for the construction of aza-heterocycles. Due to their structure

• construction of carbon–carbon bonds [5][6][7][8][9][10]. The hetero-Diels–Alder reaction is therefore an attractive strategy for the synthesis of heterocyclic compounds. It involves the reaction of dienes or dienophiles which possess a heteroatom in their structure. In this reaction, the HOMO of the diene and

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

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

• /bjoc.20.267 Abstract A new psammaplysin derivative, ceratinadin G (1), was obtained from the Okinawan marine sponge Pseudoceratina sp., and the gross structure was clarified through spectroscopic and spectrometric analyses. The absolute configuration of compound 1 was established by comparing its NMR

• , H-1/C-3, H-1/C-6, H2-5/C-3, H2-5/C-4, H2-5/C-6, H-5a/C-7, H-7/C-8, and 3-OCH3/C-3) supported the presence of the 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol unit (partial structure a in Figure 2). While the existence of the 11-N-methylmoloka'iamine unit (partial structure

• were linked via a carbonyl group at C-9. Therefore, the gross structure of 1 was elucidated. The absolute configuration of ceratinadin G (1) was assigned by comparing its NMR and ECD data with those of psammaplysin F (2), whose absolute configuration has already been established [10][11][12]. The NMR

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

• describe the large-scale extraction, isolation, and structure elucidation of four new metabolites, ianthelliformisamines D–G (4–7). Additionally, we report the isolation of the known natural products, aplysterol (8) and ianthelliformisamines A–C (1–3). Owing to the novelty of ianthelliformisamine D (4) we

• from the amide proton linked the propyl-2-pyrrolidine moiety to the brominated acrylamide fragment and thus the full chemical structure of 4 was elucidated and assigned to ianthelliformisamine D. A refined literature search using Scifinder Scholar [16] revealed that compound 4 contains a novel scaffold

• [18], thus enabling the full chemical structure of ianthelliformisamine F to be determined. The TFA salt of ianthelliformisamine G (7) was also purified as a stable brown gum. In a similar manner to compound 6, the LRESIMS indicated the presence of two bromine atoms; these data also indicated that 7

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• from isoxazole 1a and primary and secondary amines according to the conditions described in entries 9 and 10 in Table 2, with yields of up to 78% (Scheme 4). An experiment with benzylamine and isoxazole 1a on a 1.5 mmol scale gave diamide 10a in 84% yield. The structure of compound 10h was confirmed by

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

• stabilizes their secondary structure and their metabolic stability, which is useful for numerous applications [3][4][5]. Indeed, the cyclic structure considerably reduces the number of possible rotational conformers, allowing a rational control of the 3D conformational space. Among these cyclic structures

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing

• configuration of compounds 7e and 7e’ and consequently of tripeptides 8e and 8e’ (see Supporting Information File 1). Next, some preliminary conformational studies were performed. Firstly, the X-ray crystallographic analysis of compound 8f did not show any hydrogen-bond pattern and the global structure of the

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• , nucleic acids, polysaccharides, and lipids. These modifications can impact the structure and biological functions of these molecules, ultimately leading to neuronal death, as observed in conditions like AD [30][31]. Recent studies highlight OS as an early event in AD pathogenesis, and mitochondria

• improved biological activities. Employing this approach, Kushwaha et al. [34] synthesized a series of compounds containing benzofuran, tetrazole, and pyrazole within a single structure (Scheme 2). Benzofurans and tetrazole pharmacophores have demonstrated potential anti-Alzheimer activity by inhibiting

• , among others. Ugi reaction: The D2 dopamine receptor (DRD2) is the target of different drugs, including antipsychotics, antiparkinsonian agents, and addiction-related disorders. Aripiprazole and cariprazine are prototypes of newer antipsychotic drugs with a bitopic ligand structure, which includes both

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• initial measurement of 3 at 90 K revealed an unusually large unit cell (a = 7.14 Å, b = 21.38 Å, and c = 44.04 Å). Following structure solution and refinement [76], we found that 3 crystallizes in an orthorhombic space group P212121 with five symmetry independent moieties (Z' = 5) and with no solvent

• , we confirmed that a phase transition had occurred following structure determination at 240 K [78][79]. The X-ray data revealed that 3 crystallizes in the centrosymmetric orthorhombic space group Pnma in the high temperature phase (HTP) with cell axes a = 21.56 Å, b = 8.95 Å, and c = 7.28 Å, in

• temperature, it was rapidly cooled to 100 K under a stream of N2 and the larger, disordered cell was observed once more [80]. (These observations also prompted us to measure a structure of 2 at 240 K; in this case, the unit cell is virtually identical at both high and low temperatures, indicating no phase

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

• pyrrolidine intermediates A can undergo further transformations (Scheme 10), depending on their structure and the iodane reagent being used. For example, higher yields of 3-fluoropiperidine products 6 were observed when using cyclic iodane reagents 21 and 22 (Scheme 10), which was suggested to be because a

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

• (aromatic) organic heterocyclic systems, excluding calix[4]pyrroles, which are colorless and non-aromatic, as well as norcorroles, isophlorins, and the 16π oxidized form of porphyrin that exhibits anti-aromatic character (Figure 1a). Calix[4]pyrroles possess a nonplanar structure and a high degree of

• that function as hydrogen-bond donors and acceptors. Additionally, the nitrogen atoms in the pyrrole units of the porphyrin structure can also act as Lewis bases, capable of donating electron pairs. These properties enable tetrapyrrolic macrocycles to act as effective binding sites or catalytically

• , 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

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• compounds that elicited proliferation inhibition are ordered below from the highest to lowest effect on MCF-7 cell line: 18d, 18j, 18h, 18i, 18b, 18f, 18a, 18g, 18c, and 18e. Compounds 18c, and 18e did not affect MCF-7 cell proliferation inhibition. Regarding the structure–activity relationship, the

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

• systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99

• stable allenyltrichlorosilane that affords undesired homopropargylic alcohols [35][36] (Scheme 2b). Furthermore, Iseki [35] and Nakajima [36] evaluated only one chiral catalyst in their independent studies (i.e., no catalyst structure–reactivity and selectivity relationship study). In this context, we

• structure–enantioselectivity relationship is exactly opposite to that for the analogous allylation reaction reported by Nakajima [47], thus it raises a possibility that the asymmetric induction mechanism could be fundamentally different between the present allenylation with propargyltrichlorosilane and the

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

• UV range [30]. Therefore, we aimed at further modification of the core structure of bis-and tris-norbornadienes, which may lead to a more pronounced red shift of the absorption while maintaining the high energy density. As this has been shown in other cases already [34], we anticipated that the

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• recent years and new methods capable of exploring the natural product chemical space more broadly and more efficiently is in urgent need. Chemical structure metagenomics as one such method is the theme of this Perspective. It emphasizes a chemical-structure-centered viewpoint toward natural product

• research. Key to chemical structure metagenomics is the ability to predict the structure of a natural product based on its biosynthetic gene sequences, which facilitated the discovery of numerous new bioactive molecules and helped uncover oversampled/underexplored niches of decades of BGF based discovery

• . While microbial nonribosomal peptides have been the focus of chemical structure metagenomics efforts thus far, it is in principle applicable to other natural product families. The future outlook of this new approach will also be discussed. Keywords: bioinformatics; chemical structure metagenomics

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

• -0083 Tokyo, Japan 10.3762/bjoc.20.252 Abstract Owing to their dynamic natures, rotaxane-based polymers are attractive motifs for developing stimuli-responsive materials. However, the accurate control of the rotaxane structure, which can be achieved via multistep synthesis, is key to utilizing the

• . Keywords: cyclodextrin; defined structure; precise synthesis; rotaxanes; stimuli-responsive material; Introduction Stimuli-responsive materials can satisfy the existing high demands on such materials owing to their multiple functionalities (e.g., for effective energy storage or as decomposables under mild

• rough structural control. Ideally, the accurate control of the structure of a small-molecule system is directly transferred to the corresponding polymer framework to implement a defined rotaxane structure on the latter for precise property control, although an existing huge gap between the studies on

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

• the facile preparation of molecular libraries with an emphasis on skeletal diversity for the development of new push–pull molecules. Results and Discussion Synthesis and structure determination A two-step procedure was used to obtain the target compounds (Scheme 1). Cyclopenta[b]pyridine derivative 2

• File 1). Moreover, it was found that the emission band could be adjusted by about 200 nm in solution and by 270 nm in the solid state through directed protonation of the dimethylamino group. Structure of previously synthesized stilbazoles А and arylidene derivatives of pyrindane 1 reported herein. 1H

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

• hazard for metallocages and metallocontainers. The dianion is capable of competing with the ligands used for self-assembled metal-based receptors instead of being bound inside the host structure as intended. Oxalate can strip off metal centers from the designed receptor causing a full or partial

• disassembly of the host structure. Guest-driven decomplexation events can also be utilized as detection method [65][68][69][70][71][72][73] but such processes are generally not desired for containers or cages because guest binding is anticipated to take place by encapsulation while the structure of the

• well as metalla-bowls [76][77][78][79] resulting in binding constants of log K = 3.60 [76], 4.60 [77], and 3.48 [78] for oxalate binding in methanol. Additionally, a crystal structure of a positively charged copper(II) helicate with encapsulated oxalate was reported in a study with the focus on

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• involving radical intermediates from hydroperoxides under redox conditions (Scheme 3). The reactivity of O-centered radicals is less predictable and more diverse depending on radical structure and substrate pattern than the chemistry of C-centered radicals [29][30]. Generally, peroxy radicals have a

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• Mike Brockmann Jonas Lobbel Lara Unterriker Rainer Herges Otto Diels-Institute of Organic Chemistry, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany 10.3762/bjoc.20.248 Abstract In this study, novel fluorinated carboxylic acid esters of the generic structure TfO

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

• Poznań, Poland 10.3762/bjoc.20.247 Abstract The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation

• of 1-fluorobis(phenylsulfonyl)methane (FBSM) to α,β-unsaturated ketones with cinchona alkaloids [9]. Fluorinated Michael acceptors usually contain one fluorine atom or a trifluoromethyl group in the structure [10][11][12]. There are also known examples of gem-difluoroalkenes being used as Michael

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• appears, the more efficient is the induction of chirality in a nematic host. Additionally, the location of the chiral substructure within the dopant molecule seems to play a role. A more ‘central’ location within in the mesogenic core structure corresponds to a higher HTP of the resulting chiral compound

• range of chiral, twisted molecules such as binaphthyls [23][24][25], biphenyls [26][27], TADDOLs [16][17] and 1,2-diphenylethane-1,2-diol [28] to reveal possible relationships between the molecular structure of chiral dopants and their HTP value. However, quantitative structure–property relationships

• potential chiral dopants. Our long-term goal would be to provide a structure–property relationship of this class of molecules by i) modification of the aryl and ii) and/or acetal moieties (Scheme 1) and to elucidate the possible role of fluorine on their physical properties, with comparison to their non

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• compounds 1a–f and 1i were measured (see Supporting Information File 2), and data for compounds 2–4 were sourced from the literature [24][26][28]. A representative set of structural parameters obtained from XRD is presented in Table 1. All compounds show a trigonal bipyramidal structure, in which the 3

• charge on this substituent in the hypervalent bond. The long I–X distances (a = 2.758–4.165 Å) are indicative of ionic compounds, with the exception of the cyclic benziodoxolone 2, in which a covalent I–O bond is observed (a = 2.484 Å). We were unable to obtain a crystal structure of the ortho-nitro

• compound 1j. However, a previously reported crystal structure of ylid 3, which also contains an ortho-nitrobenzene substituent, suggests a pseudocyclic structure where the nitro group is coordinating to the iodine centre (a(I–ON) = 2.695 Å) [28], which we propose is likely to be the case in 1j as well. In

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

• properties of violanthrone is traced back to 1950, when Akamatu and Inokuchi measured its electrical conductivity (σ), which was found to be 3.4 × 10−4 Ω−1 cm−1 [27][28]. The chemical structure of violanthrone allows for its modification and hence the synthesis of materials with interesting spectral

• information on the molecular structure and packing of these materials. However, no significant information about the electronic and orbital distributions was provided, therefore further investigation was needed, using a more suitable basis set. The molecules were geometrically optimised at the ground state

• single-crystal X-ray analysis were obtained by slow evaporation of a dichloromethane/isopropanol solution of 3b. The crystal structure of 3b, displayed in Figure 4, shows a very similar twisted conformation of the core of the molecule to that of the related methoxy-substituted structure obtained from

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 groups attached to an iodine atom and an associated "anion". X-ray studies revealed that these iodine(III) compounds typically have a T-type structure 1 (Figure 1). In solution, they dissociate into Ar2I+ and X− counterions 2, with the degree of dissociation influenced by the solvent and the

• chemoselectivity of the product is primarily determined by the steric hindrance and electrophilicity of the aryl groups [17]. When the two aryl groups form a cyclic structure with a central iodine atom, they are referred to as cyclic diaryliodonium salts 4 (Figure 1). Cyclic DAISs are predominantly found in simple

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

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

• mass spectrometry. Taking 4h as an example for the analysis of its structure, in its 1H NMR spectrum, one singlet signal appears at δ = 0.67 (9H) corresponding to the three methyl groups in the tert-butyl substituent. A singlet at δ = 2.39 (3H) is assigned to the protons of the CH3-group on the phenyl

• studied by X-ray diffraction analysis, and the crystal structure is illustrated in Figure 2 (detailed information can be found in the Supporting Information File 1). The 1H NMR spectrum of product 6f obtained through the I-MCR was investigated and some unexpected chemical shifts were observed at room