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

• a distinct 1:1 host–guest complex was formed (Figure 2b). The major signal at m/z of 705.1282 and its isotope pattern matches with the calculated value (705.1263) of the 1:1 complex [(C2)@L2Zn2]2‒. The m/z-signal at 1652.5394 fits to a single negatively charged TBA adduct of the 1:1 complex (Figure

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

• products. The radical path was considered for the reaction mechanism as on adding TEMPO as radical scavenger the radical trapping adduct was detected by HRMS. Simultaneously with the above work, Murarka and co-workers also reported an organophotoredox-catalyzed stereoselective allylic arylation method for

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• , a secondary aniline only furnished traces of the expected product. Aliphatic aldehydes also failed to deliver the multicomponent adduct. Conclusion In conclusion, we have shown in this work that alkyl bromides can be used instead of alkyl iodides in a direct zincation–multicomponent organometallic

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• temperature without addition of acetic acid. To address this, the reaction was performed at −78 °C, and acetic acid was added at the same temperature, yielding adduct 4a in 13% yield (Table 1, entry 2). The reaction yield was significantly influenced by the amounts of 3a and butyllithium used. The yield of 4a

•  3) [13][14]. To a dry THF solution of adduct 4a, butyllithium was added, and the reaction mixture was stirred at −78 °C for 5 min. Following the addition of acetic acid, the reaction mixture was concentrated and subjected to silica gel column chromatography, resulting in the isolation of ethyl 5

• -butoxide was observed, suggesting that lithium ions activate for the ring closure. Under the conditions in Table 3, entry 3, adduct 4 underwent ring formation. This reaction was not influenced by the bulkiness of the substituent on the alkynyl group, yielding the corresponding oxazoles 5b–d (Table 3

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• published that the asymmetric conjugate addition of 4-methylphenylboronic acid towards (E)-5-bromo-4,4,5,5-tetrafluoro-1-phenyl-2-penten-1-one (8) in the presence of a rhodium catalyst coordinated with (S)-BINAP gave the corresponding Michael adduct 9 in 94% enantiomeric excess (reaction 2, Scheme 1) [22

• at room temperature for 24 h gave the corresponding [1,3]-proton shift adduct (S)-20b in 31% yield (Table 1, entry 1). In this case, the HF-elimination product 21b was also obtained in 16% [37], and the starting material was recovered in 53%. As shown in entries 2–7 of Table 1, the reactions in

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

• the 1O2 adduct of 4-oxo-TEMP (4-oxo-TEMPO) were observed in the dispersion of catC60-lip ([catC60] = 5 µM) in PBS(–) showing an evidence of energy transfer reaction by the photoexcited catC60 (Figure 5a(ii)). In the presence of electron donor (NADH) under photoirradiation, •OH generation was observed

• as a •OH adduct of DMPO (DMPO-OH, Figure 5b(ii)) revealing that electron transfer reaction was also occurring. Using DEPMPO as a spin trapping reagent, detection of O2•– was tried and some radical adducts were detected, but without being clearly identified (Figure 5c(i), (ii)). The reason of the

• inability of O2•– detection is not known at present. Upon addition of dimethyl sulfoxide (DMSO) to this system, an adduct of DEPMPO and •CH3 (DEPMPO-CH3), which was presumably generated from the reaction of •OH and DMSO, was clearly observed, further confirming the generation of •OH (Figure 5b(iii)). At the

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

• novel lipophilic cinchona squaramide organocatalyst. This organocatalyst was evaluated in a benchmark Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the Michael adduct with high yield and enantioselectivity. The hydrophobic chain of the catalyst allowed the organocatalyst to be

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

• = 5.47·104 s−1 for capturing CO2 and k2 = 4.85·10−12 s−1 for capturing the epoxide. Despite the FLP–CO2 adduct being less thermodynamically stable than the FLP–epoxide adduct (−10.1 kcal·mol−1 vs −44.8 kcal·mol−1), the lower activation barrier for the capture of CO2 and the temperature considered (273.0

• K) suggest a kinetically controlled reaction. To further shift the chemical equilibrium toward CO2 capture, increasing steric hindrance at the epoxide was explored by introducing bulky substituents into the scaffold. This resulted in an increase in activation barriers for adduct formation. Including

• differences in energy between the stationary points, the better the exploration of the catalytic space. To determine the set of scaffolds to be used for volcano plot analysis, the CO2–FLP adduct of each of the fourteen scaffolds was optimised (Figure 3). Based on the stability of the optimised adducts

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

• derivatization products by GC–MS. Failure of DMDS derivatization on unsaturated isoprenoids has been reported [21]. It has been suggested that steric hindrance of trisubstituted double bonds results in little or no adduct formation [21]. Another method for elucidating double bond positions is the formation of

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

• then attacked by the nucleophilic amidosulfinate, which also functions as an electrolyte. The amidosulfinate is generated through the formation of a Lewis acid–base adduct. A subsequent oxidation step, accompanied by deprotonation, yields the sulfonamide product. SO2 captures the excess electrons via

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 latter acting as a catalytically active species. After the addition of 1 equiv of imine 73 at −40 °C, proton Ha of 72 shifted upfield which was close to what was observed in the TfOH adduct 71, and which supported the formation of intermediate 74. The authors estimated the equilibrated ratio

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• interrupted CuAAC mechanism [65]. The thiotriazole product of this reaction, which is indistinguishable in the protein-level downstream analysis, is formed by coupling between protein free thiol groups and the triazole–copper adduct (Figure 4). However, its formation can be avoided by eliminating the free

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• center in proximity to the reactive moiety of the covalent substrate adduct to the catalyst contributes to the efficient transfer of chirality to the resulting product, even in the distant position of the 1,6-conjugated system [39]. For these reasons, iminium catalysis using primary amines appears to be

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With the

• impressive boost of the reaction rate in the ball mill was observed (3 h vs 4 days), the stereochemical outcome suffered giving the desired adduct with 59% ee instead of 94% ee in solution. Owing to the introduction of an additional functional group in the form of a thiourea moiety does not entail a

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• indicates that the formed double azide adduct is 6a, which is consistent with our previous report [18]. The double azide addition was further investigated by changing the reaction temperature. The rate constant was determined by the temperature-dependent 1H NMR spectra in CDCl3. The reaction kinetics

• outer side (in-out-ts), but the thermodynamically stable final product is a regioselective “in-in” adduct, i.e., compound 6a. Optical properties Absorption and emission spectra of 6a were measured in CH2Cl2 (Figure 5). The conjugation is changed and a highly-twisted macrocyle forms by the double azide

• were almost independent of solvents. For example, the λem in CHCl3 and THF was 514 nm (Figure S11 in Supporting Information File 1). The double benzyl azide adduct of DBA-OHex displayed similar absorption and emission spectra with a λmax of 247 nm and λem of 539 nm in CH2Cl2. Since the Stokes shift of

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• form adduct I', which is then transformed into intermediate II' by elimination of ethanethiolate. Subsequently, β-keto amide 3a is obtained when II' releases H+. Conclusion In summary, we have successfully developed an environmentally friendly method for the selective aqueous synthesis of β-keto

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -Addition of molecular bromine to phenyl isocyanide was reported by E. Kühle et al. to afford the corresponding 1,1-adduct (PhN=CBr2) [23]. Since dichloro compounds (RN=CCl2) [24] are the imino derivatives of highly toxic phosgene (O=CCl2), reactions using them as key intermediates are not safe synthetic

• ]. In the case of aromatic isocyanides, the 1,1-addition reaction is probably more likely to proceed because the C–N double bond of the 1,1-addition product 4 (R = Ar, E = PhS) is conjugated to the aromatic ring, which stabilizes it compared to the corresponding adduct with aliphatic isocyanides

• to give the corresponding 1,1-adduct (Et2P–C(=NPh)–GeEt3, 13) in 46% yield [40]. Similarly, Me2N-SnMe3 was known to add to p-tolyl isocyanide to give Me2N–C(=N–C6H4–p-Me)–SnMe3 (14) in good yield [41]. However, the authors did not specify whether the addition reactions proceeded by a radical or ionic

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• 1h–j proved also efficient for this rearrangement giving rise to the corresponding thioethers 2h–j in good NMR yields and lower isolated yield in the case of the more volatile adduct 2i. Finally, trifluoromethyl selenoxide 1k was tested as a substrate, and the rearranged product was obtained in a low

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• in most cases. A triple Michael adduct, tetrahydrochromen-4-one, is also formed as a side product in a few cases with excellent diastereoselectivity. Keywords: arylidenemalonates; curcumins; cyclohexanones; diastereoselective synthesis; Michael reaction; tetrahydrochromenones; Introduction There is

• to the increase in electron density at the carbon β to the ester group thus inhibiting the Michael addition of curcumin (Table 2, entry 4). Arylidenemalonate 2e, bearing a weakly electron-donating substituent, reacted with 1a to afford the double Michael adduct 3e in moderate yield (46%), and the

• triple Michael adduct 4e was not detected (Table 2, entry 5). Bulky 1-naphthyl analog 2f delivered the double Michael adduct 3f as the only product in a very good yield (73%, Table 2, entry 6). Heteroarylidenemalonate 2g also reacted well with 1a, affording 3g in 54% yield (Table 2, entry 7

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• absence of an electrical current, thus allowing the addition of in situ-generated HCN to the hydrazone 155. After addition of a second equivalent of sodium cyanide, the resulting HCN adduct 156 was electrolyzed under constant current to form diazene 157, which subsequently underwent addition of methanol

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• benzoyl peroxide, TEMPO, and the combination of alkyl halides with BEt3, were not applicable to this reaction. Physical properties The electronic absorption spectra of norcorrole 1 and adduct 2a are shown in Figure 3. While norcorrole 1 exhibited a weak absorption band from 600 nm to the NIR region, due

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• reacted with hexachlorocyclopentadiene at 200–220 °C within 3–4 days, forming 5,6-endo,endo-difluoro-1,2,3,4,7,7-hexachlorobicyclo[2.2.1]-2-heptene (Scheme 20) in 66% yield. At the same time, (E)-1,2-difluoroethylene, which formed the endo,exo-adduct, reacted much slower, and completion of the reaction

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• conditions were tried in a GBB reaction, no cooperative effect was observed, but even a slight decrease in catalytic activity. The use of thiamine hydrochloride as organic catalyst was reported by Yamajala et al., who were able to obtain the GBB adduct depicted in Scheme 2 (3, R = t-Bu) in 97% under solvent

• the addition of tert-butyl isocyanide. On the other hand, the addition of tert-butyl isocyanide on the imine altered the orientation of adduct 19, suppressing the interaction with Ser105 (Scheme 8). Very recently, Tyagi et al. reported the double encapsulation of CALB and Pd(PPh3)4 within silica

• adduct in more than 4 grams in a total time of 8 hours. The same amount was obtained in batch in a total time of 20 hours. 2 Novel building blocks The scope and limitations of the GBB-3CR have been accurately delineated up to 2018, outlining a comprehensive understanding of its development, observing

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• via Knoevenagel adduct formation as a first step, which may become a significant limitation of this reaction. However, we have never observed and isolated Knoevenagel adducts of aromatic aldehydes 4 and N,N-dimethylbarbituric acid (5) during the synthesis of 5-aryldeazaalloxazines 2a–x in either of

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• acid, indole-2-carboxylic acid, pyrrole-2-carboxylic acid or N-phenylglycine has allowed the use of these compounds in the Ugi reaction without triggering competitive reactions. The additional functional group present in the resulting Ugi adduct can be leveraged in different post-condensation

• chromatography column, while the more eco-friendly second strategy needs an additional stage for the reduction of the nitro group on the Ugi adduct. In order to find a more efficient synthesis, we thought that the second nitrogen in the diazepine nucleus could be incorporated without the need of surrogates or

• workup the only product observed was the corresponding benzodiazepinone 5, resulting from a spontaneous cyclization of the Ugi adduct, in a six-center four-component Ugi reaction (U-6C-4CR), which prevents the need of additional steps (Scheme 1, Table 1). Due to the interest of these results and