Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• ), it was non-scalable and displayed low modularity. Indeed, the imide groups along with their substituents were introduced at a rather early stage of the synthesis, with the ultimate synthetic step being the formation of the thiepine ring via a two-fold nucleophilic aromatic substitution by sodium

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

• hydride resulted in the formation of the oxepine ring by a double substitution reaction, to yield the desired dinaphthooxepine 33. The non-planar character of dinaphthooxepine bisimides was confirmed by X-ray crystal structure, and stability towards thermal or photoactivation was also established. Cyclic

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• nucleophilic substitution of benzylic bromides with sodium azide and a subsequent copper(I)-catalyzed double click reaction in one pot [17]. In summary, these contributions by renowned experts demonstrate the broad diversity of impressive catalytic domino, tandem, and one-pot processes towards many valuable

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• reaction with neutral or anionic bases. Keywords: dipyrido[3,2-e:2′,3′-h]acenaphthene (acenaphthylene); hydrogen bonding; π-stacking; substitution reactions; tele-elimination; Introduction Quinoline derivatives, classical nitrogen-containing heterocycles, are widely distributed in nature in various forms

• make molecule 5 (and derivatives) more rigid and flat when compared to compound 3 but it will also affect its reactivity and the sites of functionalization. This work is devoted to the clarification of this circumstance with substitution and elimination reactions chosen as the key transformations. The

• quinolines, at the benzene ring, and the resulting nitro compounds could potentially be subjected to further transformations, including nucleophilic substitution of nitro groups. Indeed, under the action of a small excess of the nitrating mixture, dipyridoacenaphthene 5 undergoes double nitration at

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• (DPT). Taking together, the main indigo scaffold is not photochromic. However, substitution of the hydrogen atom in the NH groups of indigo can change the photochemical behavior significantly. Photochromic indigo derivatives In 1954, the first photochromic indigo derivative, namely N,N'-diacetylindigo

• the photoreaction, is advantageous for applications in bulk materials because the photoisomers have decreased absorbance at the excitation wavelength [9]. Depending on the substitution pattern, the quantum yields for the E–Z photoisomerization of indigo photochromes vary from 0.001 to 0.46 and the

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• applications due to their improved solubility in aqueous systems. Assembly is achieved by integrating distinct carbohydrate, peptide, and polyprenyl phosphate building blocks. This modular synthetic method allows for the strategic substitution of constituent building blocks at different synthetic stages and

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• intermediate C is then generated, followed by the combination of the bromine anion with intermediate B. Finally, selective C5 bromination is accomplished via aromatic electrophilic substitution of 1a with intermediate C promoted by the copper catalyst to afford the desired product 3aa. Conclusion In summary

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• determined to be 2 and 58 ps, respectively. The observed longer lifetimes attributed to DEA substitution could be due to the larger distance and the Marcus inverted region [143] character, compared with the results obtained for OEF substitution. Guldi et al. synthesized zinc phthalocyanine (ZnPC) covalently

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• , both as photo-controllable DNA binder and as DNA-damaging photosensitizer. Still, some key parameters have to be optimized by variation of the substitution pattern. For example, the water solubility of the styrylpyridine substrates has to be increased, and the excitation wavelength for the

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• -annelated IF-DTF 12 by removal of the tosyl (Ts) group under alkaline conditions, followed by nucleophilic substitution to incorporate the hexyl chain on the pyrrole. Furthermore, treatment of the IF-DTF ketone 4 with Lawesson’s reagent (using a recently established protocol [20]) yielded the large dimer 13

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• of two equivalents of halogen salt waste. Their substitution with iodolium salts will be more sustainable since it reduces these unproductive halogenide salts by half. Due to our recent activity in the field of synthesis and applications of 5- and 6-membered cyclic iodonium salts, we searched for an

• possible products. We obtained p-halogenide- and p-pseudohalogenide-substituted compounds 2c–g in good yields of 76–87%. It is noteworthy that the para-chloro-substituted compound 2f is a known fluorophore [5]. The reaction tolerated methoxy- and methyl ester-substitution to give 2h and 2i in 84% and 90

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• sequencing (step 5', Figure 1). One colony (the one corresponding to lane 26) was found to have the correct full-length 399 bp sequence (see Supporting Information File 1 for sequence alignments). The sequences in the other two colonies had errors with one containing a dG-to-dA substitution, and the other

• full-length sequence. The sequences in the other two colonies had errors with one containing one dG-to-dA substitution and the other containing one single-nucleotide (dC) deletion, and one dT-to-dC and one dG-to-dA substitution. Construction of GFP gene and GFP expression in E. coli Gibson assembly was

• a dG-to-dA substitution error (see Supporting Information File 1 for sequence alignments). Plasmid DNAs, which were isolated from the clones with sequencing confirmed full length GFP gene, were transformed into E. coli Single Step (KRX) competent cells, which allow for tightly controlled gene

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• mesitylamine with sodium nitrite and acetic acid followed by a substitution of the intermediate diazonium salt with sodium azide [68]. All our attempts to prepare 2-azido-1,3-diisopropylbenzene along the same lines failed. Nevertheless, its in situ formation in the presence of phenylacetylene led to the

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• ylide B. Thirdly, the intermediate C is formed by the nucleophilic substitution of a halide ion in substrate 1 by the allylic ylide B. Then, Michael addition of the amino group to the C=C bond results in the cyclic intermediate D. Finally, the spiro[indoline-3,5'-[1,2]diazepine] 3 is produced by the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• reaction is believed to occur via electron transfer, followed by the radical coupling of La@C2v-C82 and benzyl radicals, rather than by bimolecular nucleophilic substitution reaction of La@C2v-C82 anion with 1. Keywords: electron transfer; metallofullerene; radical; reduction; Introduction Fullerenes

• transfer, followed by bimolecular nucleophilic substitution (SN2) reaction [8]. Endohedral metallofullerenes, wherein one or more metal atoms are encapsulated inside a fullerene cage, have garnered research interest [12][13][14][15]. The encapsulation of metal atoms can result in electron transfer from the

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• 5 in the presence of symmetrically substituted pyrazoles produced the relevant products of N–H insertion 6d–f in high yields. The substitution of methyl groups with phenyl groups (6d vs 6e) had no significant impact on the outcome of the reaction. The synthesis of compound 6f was conducted on a gram

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• ], drugs used to treat cystic fibrosis and HIV infection, respectively. A plethora of 4-quinolones with various substitution patterns and biological activities have been isolated from natural sources. This includes plant-derived alkaloids such as graveoline [7], evocarpine [8], leiokinine [9], evollionine

• -3 substitution in analogues of microbial behavioral modulators [54][56], prompted us to investigate a new synthetic approach that could provide a straightforward access to both 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides. Our approach falls within the broader methodological group of

• -substitution in R1 drove the yields of 3 below 50% and for this reason isolation and further elaboration of such products were considered impractical. Once prepared, the key intermediates 3 could be transformed either directly to 2-alkyl-4-quinolone-3-carboxamides 5 or to 2-alkyl-4-quinolones 8, after an

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• -functonalized stopper 3 after substitution of bromine with azide. The dialkyne-decorated pyridine 5 was prepared starting from 2,6-bis(bromomethyl)pyridine that was reacted with compound 4, under phase transfer catalysis (Scheme 1). Finally, the axle 6, as well as the reference macrocycles M1 and M2 [44], were

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• , reflux, 2 h) when anhydrous hydrazine (4.2 equiv) was used as a promoter. A plausible pathway for the transformation of imidate 4 into macrocycle 5 is shown in Scheme 3. This pathway includes fast substitution of the ethoxy group by hydrazine to give the intermediate amidrazone 7 followed by its rapid

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• vital role in shaping the next generation of electronic devices and renewable energy systems. Structures of some of the most versatile Qx scaffolds; dashed lines indicate the substitution sites for core expansion. Qx-derived polymer acceptors. Qx-derived small molecule NFAs. Qx-derived small molecule

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• aldehydes and α-amino esters (via dehydration) or α-amino acids (via decarboxylation) could be classified based on the substitution groups on the N atom to: 1) N-substituted (N–R type), 2) hydrogen containing (N–H type), and 3) metal complexes (N–M type) (Figure 1) [16][17]. These AMYs could also be

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• cations, while 4,7-dimethoxy substitution leads to more reducing E(1+/1•) values, as well as cathodic shifts in E(12•+/12) and E(1H•+/1H) values. Both the use of 3,4-dimethoxy and 2-aryl substituents accelerates the reaction of the 1H species with PC61BM. Because 2-aryl groups stabilize radicals, 1b2 and

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• the same substitution pattern as substrate 7 tend to give poor yields in similar intramolecular Heck reactions [20]. Moreover, it was found that substrates on which the halide is cis to an additional methyl substituent (used to forge the ethylidene-substituted polycycle common to many alkaloids) often

• amine protection – can potentially take place in one pot). We have shown that this protocol can be applied to the synthesis of several analogs bearing different substitution patterns on the alkene. The structural diversity that can be readily obtained utilizing this chemistry underscores the versatility

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• overwhelmingly more common in the latter because there are other more selective and efficient solution chemistry methods for post-polymerization modification, such as nucleophilic substitution [94][96]. In this section, we discuss the radical chemistry used in both processes. 3.1 Post-polymerization modification

• inert substrates. Here, radical chemistry comes into play. When polymer surfaces are modified by radical chemistry, radicals are either generated directly on the polymers or on modifiers. In the latter case, a radical addition, substitution, or coupling reaction takes place to complete the modification

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• of substitution are represented in Figure 2. The effect of the CDs on the membrane permeability was monitored by following the release of a hydrophilic fluorophore, sulforhodamine B (SRB), from liposomes composed of DPPC and different CHOL content upon exposure to different concentrations of CDs. To

• the work of Piel et al., who showed that CRYSMEB is less potent than RAMEB and other methylated CDs in promoting calcein leakage from liposomes comprising 30% CHOL [13]. The authors stated that the low degree of substitution of CRYSMEB decreased its affinity to the lipid membrane components and

• and SBE-β-CD are active on CHOL-poor membranes. The effects of β-CD derivatives obtained in this study present a good correlation with biological membranes studies: the methylated β-CD derivatives with high degree of substitution (RAMEB in our study) possess the strongest CHOL extraction capacity and

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• cycloaddition or addition–elimination reactions with 1,3-dipoles and gem-difluoroalkenes is largely unexplored and the only report of a cycloaddition is with 2-fluoroindolizines (Figure 1A) via a β-fluoride elimination in an SNV (nucleophilic vinylic substitution)-like transformation [9]. Nucleophilic addition

• and benzyl azides was examined. An array of para- and meta-substituted aryl azides was amenable to the optimized conditions. The presence of electron-withdrawing groups worked well affording the products with m-cyano (4a), 3,5-dimethoxy (4b), m-fluoro (4c), and p-chloro (4d) substitution in 39–58

• azido amine intermediate INT-3 can be formed via vinylic substitution of INT-1 with an azide which can cyclize to form INT-4 that subsequently aromatizes to afford product 3 (route B). To demonstrate the applicability of this method, a scale-up reaction was performed using 150 mg of the limiting reagent