Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• produce a wide range of bis(indolyl)methanes 28 in good to excellent yields (62–93%) [93][94]. Regarding the mechanism of action of this methodology, two halogen bonds are formed between the bidentate halogen-bond donor 26 and the oxygen of the carbonyl group (Scheme 12). This increases the

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• . Radical intermediate 9 formed upon fragmentation of 25, adds to the styrene acceptor forming radical 26. Finally, a radical-polar crossover event between 26 and the IrIV complex regenerates the IrIII ground state while delivering cation 27 that is then trapped by the oxygen-nucleophile to form the

• ] (Scheme 7A). Cyclic voltammetry measurements of a model NHPI ester showed a shift in its reduction potential from –1.79 V to –1.51 V (vs SCE in MeCN) in the presence of In(OTf)3. As such, it was hypothesized that the Lewis acid lowers the LUMO of the NHPI ester via interaction with the oxygen lone pair in

• electron reduction of 58, generating the persistent radical 147 and the transient species 148, which fragments into tert-butyl radical (64). Notably, the reduction of NHPI ester 58 could be facilitated by interaction of a cesium cation with the oxygen lone pair of the phthalimide, in analogy to the

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• would lead to steric clashes and loss of strong hydrogen bonding. In the LacNAc-complexed structure (PDB ID 8R8A) [29], the GlcNAc residue did not seem to engage in extensive interactions, with only a hydrogen bond between the N-acetyl moiety and the main chain oxygen of Gly24 and hydrophobic

• . While no direct interactions with the protein backbone were observed, we found one water molecule to mediate hydrogen bonding between the oxygen of the N-acetyl group and the Asn43 side chain oxygen (Figure 4d). Both GalNAc anomers could be observed, showing interactions through water molecule

• coordination with the Trp36 ring nitrogen (alpha anomer) or the Gly24 main chain oxygen (beta anomer). Conclusion Our work presents a substantial exploration of the binding specificity and mechanism of the hitherto uncharacterized lectin CMA1 from melons. The binding specificity of CMA1, C2-substituted

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

• the synthesis of a series of HBC precursors incorporating a group-16 heteroatom embedded in a seven-membered ring. In the case of oxygen, the fully cyclized HBC 26a containing an oxepine ring and exhibiting a saddle-shape tridimensional structure was successfully prepared (Scheme 8, top). Conversely

• the corresponding planar HBC at room temperature upon acidic treatment under air, thus triggering SeO-elimination as well as cyclodehydrogenation in a single step. As mentioned above, oxepine derivatives display higher stability compared to other chalcogen heteropines and direct oxygen extrusion from

• oxepines under photo- or thermal activation has not been reported. Oxygen thus appears as the chalcogen element of choice to obtain stable heteropines embedded in π-CPCs and study the properties of such non-planar compounds. Very recently, Fukui, Shinokubo and co-worker reported the synthesis of

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

• lifetimes, radiative and non-radiative relaxation pathways of the indigo chromophore [26][27][30][31][32][33][34][35] as well as to estimate ionization potentials and electronic structures [28][29], singlet oxygen generation capacity [31], QSAR properties [25], and others. In both solution and solid state

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• (1a), followed by the oxygen-promoted insertion of the phenylboronic acid coupling partner 7 to deliver intermediate II that undergoes reductive elimination to give diarylamine 3a along with regeneration of the copper catalyst (Scheme 5). Then, a palladium-promoted oxidative addition of the C–Br bond

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• versus α:β = 13:1 for 2). One could speculate that a more nucleophilic carbonyl oxygen of the chloroacetyl group at O-9 in sialyl donor 2 might participate in a stabilization of the intermediate glycosyl cation from the α-side (as we discussed earlier [52][53]) diminishing the α/β ratio. Conversely, at

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

• (tetraphenylporphyrin performed equally well but was harder to separate from the products) and irradiated by white LED light under an atmosphere of oxygen. It led to a mixture of unseparable regioisomeric allylic hydroperoxides 2 and 2’ (≈2:1) that were not isolated for instability reasons, but directly engaged in the

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• moderate to good yields. Experimental To a vial equipped with a stirring bar, alkene-tethered indole substrate 1a (0.3 mmol), Umemoto's reagent (2b, 0.1 mmol), and DCM (2 mL) were added. Then, the vial was degassed and backfilled with N2 three times to remove oxygen. The reaction mixture was stirred at

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

• , even under anaerobic conditions. Investigations of the mechanism of the DNA damage revealed the involvement of intermediate hydroxyl radicals and C-centered radicals. Under aerobic conditions, singlet oxygen only contributes to marginal extent to the DNA damage. Keywords: DNA intercalators

• 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

• species (ROS), such peroxyl, alkoxy and hydroxyl radicals, or carbon-centered radicals, which subsequently induce DNA strand cleavage. In the type-II mechanism, a triplet-excited photosensitizer reacts with molecular oxygen to give highly reactive singlet oxygen, 1O2, as reactive intermediate, which in

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

• for the used micro GC (DynamiQ-S, Qmicro B.V.) and as inert gas to remove the oxygen in the reactor. Before the light source was turned on, argon gas was purged into the solution to remove dissolved oxygen. During the reaction, a constant argon flow was set with a mass flow controller (MFC, F-201CV

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

• was observed for compound 27 was also observed for this compound. The degradation of compound 20 in the presence of light and oxygen is visible as a color change upon leaving a sample of the compound in solution in an open vial, unshielded from light (Figure S2 in Supporting Information File 1). This

• degradation was investigated by UV–vis absorption spectroscopy; the absorption spectrum was measured over time for three different samples, and a notable change in the longest-wavelength absorption maximum was only observed for the sample that was exposed to both light and oxygen (see Figures S3 and S4 in

• Supporting Information File 1). We speculate that this degradation is due to the reaction with singlet oxygen generated by the compound as a photosensitizer; indeed, we have recently shown [31] that IF-TTF compounds are reactive towards singlet oxygen at the central fulvene bond but, in contrast, IF-TTFs

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• adducts 2a–i, the carbon atom 1, featuring the phenolate oxygen atom attached, shows a doublet (2JPC ≈ 4 Hz) in the range of 175.0–173.9 ppm (Table 1). In the closely related 2,4-di-tert-butyl-6-(triphenylphosphonium)phenolate the chemical shift for the corresponding carbon atom appears at 173.8 ppm (2JPC

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

• anions could coordinate the Lewis acid BF3 through the negatively charged oxygen [107], decreasing availability of BF3 for catalysis. Otherwise, ILs possessing bis(trifluoromeylsulfonyl)imide and hexafluorophosphate anions afforded hydrated product 2a with slightly better yields (87%) compared to those

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

• toluene, and (c) (Cyc-DMBI)2 in toluene with excitation at 350 nm in the absence of oxygen. (d) Comparison of temporal evolution of the absorption at 654 nm for both dimers in toluene. (e) Spectra for the two monomeric radicals obtained from M06/6-31G(d,p) TD-DFT calculations. Selective deiodination of 2

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• groups to achieve optimal charge-transporting and fluorescent properties within one TADF compound (Figure 1) [5]. The obtained TADF emitters (453 to 550 nm) show photoluminescence quantum yields of up to 98% in oxygen-free toluene solutions. These TADF emitters are suitable for OLEDs with brightness of

• solutions of compounds 6–9 is increased after deoxygenation by argon (Figure 3a and Figure S2a in Supporting Information File 1). The increase of PL intensity is attributed to a delayed fluorescence turn-on when the triplet quenching by oxygen is omitted. This delayed fluorescence is TADF in nature as it is

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

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• ][35][36]. Our lead compound INHHQ (or 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone) has been successfully tested in the prevention of short- and long-term memory deficits in a mice model of sporadic AD [33]. Additionally, INHHQ decreases copper-mediated production of reactive oxygen

• different space groups. The methyl-containing hdz-CH3 crystallized in the monoclinic system, C2/c space group, while the nitro derivative hdz-NO2 belongs to the group, from the triclinic system. In both cases, a moderate to strong intramolecular H-bond involving the phenol oxygen O1 as H-donor and the

• , nitro and azomethine) compete for the delocalized negative charge coming from the ortho phenolate oxygen. Even though the azomethine group has a weaker deactivating effect on the ring than the nitro group, the electron density obtained by it through this mechanism increases the basicity of the N1 atom

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• cations), forming coordination compounds wherein the central ion acquires a square planar [14], square pyramidal [15], or an octahedral coordination environment [16]. On the opposite side, crown ethers are cyclic molecules composed of carbon and oxygen atoms forming the macrocycle. Depending on the size

• /electrostatic interactions [18][19][20]. Replacing oxygen atoms with other elements, such as nitrogen, sulfur, etc., alters the crown ethers' affinity toward cations, extending their role as macrocyclic ligands to transition metals [21]. One can say that in many aspects, porphyrins and crown ethers are

• included the binding of caesium cation in the oxygen-rich crown ether segment, with the fluoride interacting with NH of calix[4]pyrrole. Additionally, receptor 5 formed an unprecedented 2:2 complex with CsCl, which included two different ion-pair binding sites, whereas with the addition of CsNO3, a 1:1

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

• glycoprotein (≈1–2%), laccase (≈0.2%), and stellacyanin (≈0.02%) [6][7]. Urushiol is the main active coating-forming ingredient of the resin. A typical urushiol is shown in Scheme 2. In a humid and warm environment, urushiol absorbs oxygen from air and is oxidized to a phenolic oxygen free radical under the

• is oxygen tolerant and can be carried out in a milder environment [65][66]. Pan and co-workers recently further advanced the RAFT techniques by allowing them to be fueled by oxygen [67]. The mechanism of a RAFT polymerization is shown in Scheme 6 [68]. Organometallic-mediated radical polymerization

• as reverse iodine transfer polymerization (RITP), which is similar to reverse ATRP. The mechanism of the RITP is shown in Scheme 8. RDRP is applicable to a wide range of monomers and the reaction conditions become milder and more versatile with emerging techniques, such as oxygen tolerance or even

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

• nitrite as a nitrogen-oxygen source, and solely using aluminum trichloride as the additive. This approach circumvents the need for costly or highly toxic transition metals and presents a novel pathway for the synthesis of isoxazole derivatives. Keywords: aluminum trichloride; Lewis acid; isoxazole

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• transferred from the hydroxy group of R[4]A to the amine molecule, forming a hydrogen bond between the proton of the positively charged amino group and the oxygen anion in the R[4]A molecule (ArO−···H+NHR2). For sec-amine molecules such as morpholine and N-methylpiperazine, an “out” complex is formed by

• and the pyrrolidine molecule are marked in green, 1.478 Å in DMSO and 1.565 Å in CHCl3. Additionally, the lengths of hydrogen bonds between the protons of the hydroxy groups and the oxygen atoms in the upper ring of R[4]A are marked in purple. It is worth noting the significantly shorter length of the

• hydrogen bond between the oxygen anion of the hydroxy group (which also forms a hydrogen bond with the amine molecule) and the adjacent hydroxy group in DMSO in the R[4]A (1.505 Å) molecule than the remaining intramolecular hydrogen bonds. In CHCl3, both the type and length of the hydrogen bond undergo

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

• ) protein [16][17], as well as perturbing carbohydrate metabolism to generate reactive oxygen species that damage the DNA [18], as modes of action for berberine’s antibacterial effects. The antitumor properties of berberine have been attributed to DNA binding, and in particular regulating the activity of

• B2 showed one less aromatic proton than expected and mass spectrometry revealed the presence of an extra oxygen. It was initially thought this unexpected oxidation had occurred at position-8, leading to an 8-oxoberberine variant. However, oxidation at position-8 was questionable (qualitatively) as 8

• these optimized conditions still resulted in exclusive isolation of B2 with no evidence of the product lacking the oxygen at position-13. Subsequent variants B7 and B8 were synthesized as the expected berberine derivatives, without formation of the oxidation byproduct. Of this initial set of berberine

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

• mechanisms for the cyclization of compounds 1 and 2 into indanones 3 in TfOH (Scheme 7). Protonation of the carbonyl oxygen of enone 2 gives rise to cation B which is followed by cyclization into indanone 3 through mesomeric form B'. The hydroxy ketone 1 is protonated at the oxygen atoms leading to cation A

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• enolate and a new R• that propagates the radical chain (Scheme 1). Initiation occurs upon oxidation of the dialkylzinc reagent by oxygen. The feasibility of such 1,4-addition reactions is fully reliant on the ease of the intermediate enoxyl radical to undergo alkylzinc-group transfer. Secondary α-carbonyl

• coordinated to the zinc atom: this offers a gain in enthalpy associated to the formation of zinc enolates stabilized by chelation and increases the spin density delocalized at the oxygen atom involved in the chelate. Note that the reported 1,4-additions of dialkylzinc reagents to alkylidenemalonates could

• only they demonstrate that the oxygen-promoted 1,4-addition of α-(aminomethyl)acrylates with free N–H bonds is a productive process, but also that the tert-butanesulfinyl moiety is well tolerated and that 1,4-stereoinduction can be achieved. Hence, in order to improve the levels of diastereoselectivity