Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• mention that allylic hydroperoxides are conveniently produced by the photooxygenation of alkene substrates [14][15][16]. Taking all these informations together, since alkenes can be easier intermediates than aldehydes to handle, we envisaged to use a prenyl (= 3-methyl-2-buten-1-yl) group as an aldehyde

• surrogate of the aldehyde function when it is engaged in a tandem photooxygenation and Hock rearrangement, involving allylic hydroperoxide intermediates in an acidic medium. In the presence of aromatic nucleophiles, the aldehyde intermediate of the Hock rearrangement can be involved in tandem Friedel–Crafts

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

• manner, ultimately affording 27 with 90% yield. The formation of intermediates 24, 25, and 26 was elucidated through 1H NMR analysis, of which 24 and 26 were successfully isolated and characterized. A comprehensive analysis of the [2 + 2] CA–RE reaction activation parameters via 1H NMR spectroscopy

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

• cancer [39], and bacterial, fungal, parasitic and viral infections [40][41]. In general, PDT operates on the basis of a photosensitizer, which generates reactive intermediates upon irradiation [42][43][44][45]. Hence, in the type-I mechanism the photosensitizer induces the formation of reactive oxygen

• formation of different intermediates in the reaction sequence starting with E–Z isomerization, followed by photocyclization and subsequent oxidation. In general, the photoreaction was more efficient in polar, protic aqueous solvents (cf. Supporting Information File 1, Figures S2B–S6B) or in buffer solution

• intermediates (Scheme 4). Under anaerobic conditions, the DNA damage is similar to the one observed with the isomeric benzo[c]quinolizinium ions [35]. In the latter case, it has been shown that frank DNA-strand breaks are induced by hydroxyl radicals, supposedly formed by photoinduced electron transfer (PET

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• singlet state [10]. Although only a few analyses of the reaction mechanisms have been studied due to the complexity of the system, several intermediates inside the CNT have been proposed [3][11][12], which may be different from those proposed to take place in the gas phase or in the solid state at high

• can also be activated through the formation of C60+• radical cation [3][9]. This mechanistic proposal for phase 1, which to our knowledge has not yet been explored in detail inside a carbon nanotube, is analyzed here and compared to the non-activated C60 dimerization. Finally, some intermediates for

• -TEM images and movies will provide us a deeper understanding of fullerene coalescence processes in peapods. Computational Methods The Amsterdam Density Functional (ADF) code [21][22] was used for the electronic structure calculations and to optimize reactants, products, intermediates and transition

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• intermediates at higher intensities [37]. For further studies, the reactor setup was equipped with four heat sinks around the reactor, each equipped with 6 LEDs. This was the constructive maximum of LEDs that could be installed and allowed for providing a maximum photon flux of 32.77 µmol s−1 to the reactor

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• ]. Considering the intrinsic ionic nature of ILs, they act as very different chemical medium compared to molecular solvents, having the possibility of stabilizing charged or dipolar intermediates. Therefore, ILs can be used to modulate outcomes for some chemical reactions [82][83]. There are only a few reported

• experiments were carried out under the conditions reported in entry 9 of Table 1, in order to observe possible variations in the yield of compound 2a. ILs with different anions or cations (compared to BMIm-BF4) were investigated to probe potential interactions with the reagents, the intermediates or the

• vapour pressure and for the possibility of its recycling, but also for its ability to stabilize ionic or polar intermediates, improving the reaction efficiency. Hydration of different alkynes catalysed by BF3·Et2O in BMIm-BF4 Subsequently, the developed method was extended to different alkynes, both

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

• heterocycles; zwitterions; Introduction Following the seminal discovery from the group of Arduengo, who isolated and fully characterized 1,3-di(1-adamantyl)imidazol-2-ylidene in 1991 [1], stable divalent carbon species have evolved from fleeting intermediates to ubiquitous catalysts, ligands, and reagents in

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• ; reduction; reductive dimerization; Introduction Reductive dehalogenation reactions of organic halides can be used in organic synthesis as a means of generating carbon-centered radical or anion intermediates and could have relevance to the treatment of waste halogenated polymers. While such reactions can be

• ) that simple one- or two-electron donors capable of exergonic ground-state electron transfer to these substrates will be rather air sensitive, complicating their handling and use. In addition some molecular reductants can themselves react with the reactive intermediates; for example, the dehalogenation

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• -energy intermediates, such as benzenediazonium-2-carboxylate, and yields that are comparatively low [20]. After the Ullmann reaction was successfully employed for the first reported synthesis of biphenylene [15], subsequent studies have explored various transition-metal-mediated coupling reactions using

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• tested anion–π catalysts. This result was consistent with the stabilization of the anionic intermediates IX and X and the respective transition states on the polarized fullerene surface. Anion–π autocatalysis on fullerenes The autocatalysis of epoxide-opening ether cyclization on π-acidic aromatic

• intermediates and anionic transition states on top of fullerenes dimers should thus induce a larger macrodipole which should in turn strengthen their binding to the expanded π system and thus increase anion–π catalysis (Figure 1B). Fullerene dimer 37 was equipped with the tethered tertiary amine needed to

• deprotonate the substrate 4 and produce the conjugate bases I and II as the first reactive intermediates directly on the active π surface (Figure 2 and Figure 7) [80]. Calibrated against triethylamine 23, fullerene dimer 37 catalyzed enolate addition with an A/D37/23 = 12.5. This is more than twice the A/D22

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

• group (Figure 2). We observed formation of complex mixtures in the case of δ-valerolactam, glutarimide and oxindole. This observation can be attributed to the competing direction of the attack of the carbenoid onto the carbonyl oxygen atom resulting in unstable intermediates. In the reaction with 5

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• reaction mechanism of the presented method was studied on model reactions by electrospray-ionization time-of-flight (HRESI–TOF) mass spectral analysis in a timely manner. The analytical results indicated that the observed azafulvene-ended di- and tripyrrolic intermediates are responsible for the formation

• ), corresponding to the intermediates I–VI, respectively (Figure 1, Figures S46 and S47 in Supporting Information File 1). At the very first two minutes of the reaction run at 0 °C no mass signals attributable to reaction intermediates were observed but only signals of the starting materials 1 and 2d both in the

• negative and positive ion mode. After two minutes, tripyrrane sulfonamide II and azafulvene I mass peaks were observed. Later on, tripyrrolic intermediates III and VI predominated and the mass peak of IV was observed with poor intensity in the spectra (Figure 1 and Figure S47 in Supporting Information File

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

• reductive cyclizations of o-nitrobenzoyl ketones [57][58], enamines [59][60], or isoxazoles [61]. The scope of these reductive cyclizations is limited by the availability of the necessary intermediates and has remained largely underexplored, especially with regard to 4-quinolones with long-chain

• key o-nitrobenzoyl intermediates 3 in a reaction with o-nitrobenzoyl chloride (Scheme 1, conditions ii). The acylation of 2 to 3 proceeded with variable yields, depending on the substituents R1 and R2. Derivatives 2 with a primary carboxamide group (R2 = H) gave generally lower and poorly reproducible

• -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

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• ], it was proposed that the decarboxylative cascade cyclization reaction proceeded through the formation of a charge-transfer complex (CTC) II involving PPh3, NaI, and NHP ester 3 (Scheme 20). Upon photofragmentation of the CTC complex II, two important intermediates were generated: an alkyl radical A

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

• . Synthesis of the key intermediates 6 and 8 and of the reference macrocycle M1. Synthesis of [2]rotaxanes R1 and R2. Supporting Information Supporting Information File 18: Copies of NMR and HRMS spectra. Acknowledgements We thank Dr. Arnaud Gautier for providing us the catalyst used in CuAAC reaction and

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

• , intermediates A, C, D, and hydrazine. Figure 1 shows that the hydrazine-promoted transformation of pyrazolopyrimidine 8 into macrocycle 5 in MeOH is a thermodynamically favorable process. Moreover, the extremely low solubility of macrocycle 5 makes the dimerization of 8 even more preferable. It is noteworthy

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 alkenes. The first cycloaddition products 3c or 3d can also be used as intermediates for other transformations to synthesize novel heterocyclic rings via multicomponent, one-pot, and stepwise synthesis [63][64]. Presented in the following sections is our work on the development of amino acid

• maleimides in MeCN at 110 °C for 6 h afforded the corresponding monocycloaddition compounds followed by acylation to yield intermediates 22. The subsequent sequential Staudinger/aza-Wittig reaction of intermediates 22 gave products 23a–g in 48–75% yields with 5:1 to 6:1 dr (Scheme 14). This one-pot reaction

• ]isoquinolines. The reaction of 2-bromobenzaldehydes, 2-aminoisobutyric acid, and maleimides in MeCN under the catalysis of AcOH at 110 °C for 6 h afforded the cycloaddition products 26. The purified intermediates were used for the one-pot N-allylation with allyl bromide to afford intermediate 25 followed by a

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• derivatives; sodium nitrite; transition metals; Introduction The isoxazole derivatives not only exist in many natural products [1][2][3] and pharmaceutical intermediates [4][5][6][7], but also have great application values in organic synthesis [8][9] (Figure 1). In the past decades, many methods have been

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• have been reported [32]. The importance of dibenzo-α-pyrones is manifold as they can also be used as key intermediates in the synthesis of therapeutic compounds [32]. Since compound 1 was isolated as a racemic mixture, while compound 2 is a diacetylated derivative of the mycotoxin alternariol known for

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

• . Proposed mechanism. Scale-up experiment. Optimization of reaction conditions.a Supporting Information Supporting Information File 2: General information, experimental procedures for all the substrates and intermediates, characterization data, and NMR spectra (1H, 19F, and 13C NMR). Funding Research

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• synthesis began with the generation of substituted 2-bromo-1-aminonaphthalenes 9 and 10 (Scheme 6). After α-bromination of tetralones 1 and 2, intermediates 3 and 4 underwent elimination/aromatization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford 2-bromo-1-naphthols 5 and 6 in fairly good yield

• through the use of additional NaOH and refluxing the crude alkylation mixture. After heating for 3 h, the desired intermediates were recovered in acceptable yields over this two-step one-pot sequence. The amide hydrolysis of 7 and 8 to the desired free naphthylamines 9 and 10 proved challenging, but was

• complete decomposition. With the desired naphthylamines in hand, we were able to complete our synthesis of four chelerythrine variants as shown in Scheme 7. After N-formylation providing intermediates 11 and 12 in good yield, a three-step sequence was performed: Suzuki coupling of the aryl bromide with one

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• cyclization reactions involve a number of carbocation intermediates. In some cases, these carbocations are stabilized by through-space interactions with π orbitals. Several terpene/terpenoids, such as sativene, santalene, bergamotene, ophiobolin and mangicol, possess prenyl side chains that do not participate

• side chains has been studied by Tantillo and co-workers [24][25][26]. They reported that the carbocation intermediates traversed in pinene/camphene and ylangene/sativene biosynthesis change depending on the presence or absence of prenyl side chains. In their study, it was argued that the extent of

• investigated the biosynthetic pathways using DFT calculations to validate the above-mentioned aspects. Results and Discussion The detailed structures of the intermediates and transition states were elucidated by computational analysis. Interestingly, we have found an interaction between the secondary

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• functional materials and indispensable synthetic intermediates in drug discovery [31][32][33]. Because of their value, constructing C–S bonds has attracted significant attention via metal-catalyzed cross-coupling reactions and metal-free C–S bond formation [34][35][36][37]. Direct sulfenylation of the C–H

• in the presence of TEMPO, followed by insertion of an isocyanide molecule 166 or other nucleophiles 161 (Scheme 72) [102]. By studying the spectroscopic evidence, the authors found that both sulfenyl halide 165 and N-sulfenylsuccinimide 1 intermediates were involved in the reaction. Removal of TEMPO

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• -enones) undergo intramolecular transformation into 3-trichloromethylindan-1-ones (CCl3-indanones) in Brønsted superacid CF3SO3H (triflic acid, TfOH) at 80 °C within 2–10 h in yields up to 92%. Protonation of the carbonyl oxygen of the starting CCl3-enones by TfOH affords the key reactive intermediates

• that the formation of dications D does not take place. Species B should be the key reactive intermediates that undergo cyclization into indanones 3 with a negative Gibbs energy of −7 kJ/mol for the reaction Ba→3a. According to the calculations, the subsequent complete protonation of the hydroxy group

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• primary, secondary, and tertiary alkyl halides. The mechanistic investigation revealed the generation of a silyl–copper intermediate which activates the alkyl halides by a single electron transfer to form alkyl radical intermediates [54]. It was suggested that substituting B2pin2 for PhMe2Si-Bpin would