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

• mainly include: nucleophilic addition or nucleophilic substitution with H2O2 or ROOH [17][18], autoxidation with O2, pericyclic reactions of unsaturated bonds with O3 or O2, and metal-catalyzed peroxidation (Isayama–Mukaiyama hydrosilylperoxidation [19][20], for example) [21][22][23]. As the topic is

• styrenes 217, oxygen sources (water or alcohol), and TBHP mediated by ammonium iodine has been developed (Scheme 68) [137]. Addition of the tert-butylperoxy radical to alkene 217 followed by SN2 nucleophilic substitution with O-source was considered as a possible pathway to the formation of products 218

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

• 20 in a yield of 89% [13]. To convert the iodo to an OH group, compound 20 was reacted with Cu2O, 2-pyridinaldoxime and CsOH to give 2-hydroxy-3,4,5-trimethoxybenzaldehyde (21, 65%) [13]. In a subsequent nucleophilic substitution, the fluorinated alkyl chains of 16, 17, and 18 were linked via a

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

• was to be evidenced by a substitution reaction at the alpha position. We started testing the different bases with lithium bis(trimethylsilyl)amide [39]. The reactions did not take place in the presence of LiHMDS (Table 1, entries 1 and 2), using either benzyl bromide or methyl iodide as electrophiles

• also tried to perform a substitution reaction by treating compounds 1a and 2a with tert-BuLi, employing methyl iodide as the electrophile. However, similar to previous reactions, this did not yield substitution products at the alpha position, but to the addition–elimination reaction products. More

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

• -donating groups. The reaction exhibited high selectivity, with substitution at the C3 position not impeding the reaction. Different substituted diaryliodonium tetrafluoroborates were also investigated, yielding good product yields. The above protocol for the arylation of pyridine N-oxides 28, resulted in

• electron-donating substituents at the para-position of the N-arylacrylamide led to good yields. In cases of meta-substitution, a mixture of C6 and C4-substituted oxindole products were obtained, whereas ortho-substitution resulted in the desired oxindoles in moderate yields. Nitrogen substitution was also

• compounds (Scheme 16) [68]. The novel iodine(III) intermediate was generated through nucleophilic substitution of a heteroatom nucleophile, which initiated the reaction. A subsequent aryl migration from the iodine to the heteroatom resulted in the formation of the arylated nucleophile. In addition to

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

• electron-donating substituents (Scheme 3). The cause of this phenomenon is probably related to the electron-widthdawing effect of these substitution groups in olefin, which affects the nucleophilic attack of the isocyanides. When a carboxylate substituent was present instead of the carbonitrile in the gem

• benzoxazepine, the presence of an electron-withdrawing group leads to an increase in the yield of pyrrole-fused triazolobenzodiazepines whereas electron-donating groups led to a decrease in its yield. Also, the substitution of naphthyl used in gem-diactivated olefins increased the efficiency of the desired

• product compared to the substitution of phenyl (Scheme 4, 6c). Furthermore, n-butyl isocyanide was used to increase the variety of products and the n-butyl-substituted products 6f–h were obtained with 72–78% yield . All the products were characterized by 1H NMR, 13C NMR, and infrared spectroscopy, and

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• further substitution directly on the meso- or a meso-phenyl ortho/meta/para positions of a porphyrin, is the introduction of C–C bond forming chemistry. This is typically achieved using palladium and/or another transition-metal catalyst [20]. Sonagashira [21], Suzuki–Miyaura [22], Heck [23], Stille [24

• ][25], Negishi [26], and Kumada [27] coupling reactions, as well as modern iridium and rhodium-based coupling techniques [28], are just some examples of the C–C bond formations that have been implemented to achieve complex substitution patterns and functional arrangements on porphyrins. Of these named

• )(acac)2 under an inert atmosphere [43] attaining a 18%, 28%, and 29% yield for porphyrins 11, 12, and 13, respectively, over two steps. Porphyrins 6 and 13 had previously been described in literature [43]. Coupling at the meso-para-phenyl position The exploration of aryl substitution of OET-xBrPPs using

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• expand the scope of transition metal-catalyzed substitution reactions. Since its discovery in 2022, copper-catalyzed yne-allylic substitution has undergone rapid development and significant progress has been made using the key copper vinyl allenylidene intermediates. This review summarizes the

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

• terminal alkyne is the active species in the reactions. In this regard, merging the unique feature of Cu-catalyzed propargylic substitution with allylic substitution is a feasible solution to the challenge, which will represent a new sort of substitution reaction. From 2022, the Cu-catalyzed yne-allylic

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives. Keywords

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• likely by nucleophilic aromatic substitution during aqueous workup. Interestingly, electron-donor groups, such as N,N-dimethylamino, proved to be beneficial in terms of yield when they are located at the alkyne-linked aryl group (Scheme 4a). In contrast, the N,N-dimethylanilino group is disadvantageous

• properties All synthesized compounds exhibit photoluminescence by excitation with UV light. Hence, we studied the photophysical properties of all obtained derivatives 5 by steady-state absorption and fluorescence spectroscopy. The influence of the substitution pattern on the photophysical properties is

• presence of only one donor group is advantageous. Interestingly, the quantum yields of 5a (12%), 5g (13%), 5h (8%), and 5i (3%) are comparatively lower than in case of 5g and 5f. It is reasonable to assume that this large difference is caused by the chosen substitution pattern and can be used for further

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

• successfully synthesized on a gram scale through a three-step reaction sequence. The process began with 2,6-diisopropylphenylamine, which underwent alkylation, formylation, and substitution reactions. The carbene synthesis was then achieved via a two-step process involving ynamide annulation, followed by

• substitution (SNAr) reaction between 2-chloro-6,7-dimethoxy-4-sulfonylquinazoline derivatives and NaN3, while the second involved an SNAr reaction between 2,4-dichloro-6,7-dimethoxyquinazoline and alkyl/arylsulfinates, followed by substitution with NaN3. Using this developed methodology, the adrenoblockers

• nucleophilic substitution reaction between cyanuric chloride and 4-aminophenylphosphonate or 4-hydroxyphenylphosphonate derivatives. These synthesized dopants were used to prepare the modified Nafion membranes using a casting methodology. Almodovar and Tomé reported the synthesis and characterization of nine

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

• into readily available substrates such as epoxides, resulting in the formation of polycarbonates or monomeric cyclic carbonates [22]. Depending on the substitution pattern in the epoxide, a chiral centre is present in the product. The insertion of CO2 into epoxides has been the subject of numerous

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• UV-protector, or its metabolites, have been associated with estrogenic activities [7]. A further structure–activity relationship study revealed that a 5-substitution decreases estrogenic activity. Similar results were obtained in another study where 2-hydroxy-5-methylbenzophenone was found to exhibit

• substitution at the 4-position of benzofuranone hindered the reaction, leading to a very poor yield of the desired benzophenone product. Further, to confirm the structure and the substitution pattern in the 2-hydroxybenzophenones, single crystal XRD data were collected for the representative compounds 4ja, 4fb

• a bulky substitution at the 7-position of the benzofuranone also hinders the formation of 2-hydroxybenzophenone, we prepared 3,7-diphenylbenzofuran-2-one (3ma). However, on heating 3ma with Cs2CO3 in THF, the corresponding benzophenone 4ma was obtained, which confirmed that a bulky substituent in

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• not increase the yield of pyridine 11 further (Table 2). Despite the numerous works in the field of peroxydisulfate oxidation, there is still no unified view of the reaction mechanism. Consequently, in [31], the assumption of an electrophilic substitution mechanism for the Elbs and Boyland–Sims

• reactions was made. It has been suggested that a nucleophilic substitution of the peroxide oxygen atom occurs in peroxydisulfate [32]. Regarding phenols (Elbs reaction), there is also a nucleophilic substitution of the phenolate ion. For aromatic amines (Boyland–Sims reaction), a neutral nitrogen atom of

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• -amines and it was exemplified through the preparation of a focused chemical library with 19 members. In addition, the cytotoxicity assays afforded interesting results demonstrating that the substitution on the anilino part can have significant effects on their bioactivity. Two molecules (4a and 4i

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• +) cations, used as visible light fluorescent dyes, have been synthesized via a nucleophilic aromatic substitution (SNAr) reaction with primary alkylamines (e.g., 1a+; Figure 1) [15][16]. The highly planar geometry of the TATA+ core unit induces π–π stacking structures in single-crystal and film states, as

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• ring. A similar result was also obtained with dimethoxy-substituted phenyl moiety (2n) affording 3n with a slightly lower yield of 74%. The substitution at C5-position on the furan ring in furfuryl alcohol derivatives were further investigated. A methyl group at the 5-position (2o, 2p) resulted in the

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• . Across all tested substrates, nucleophilic attack predominantly occurred at the homobenzylic position, leading to the regioselective formation of clavam derivative with 2-benzylic substitution due to aryl stabilization of the radical intermediate (see mechanistic discussion below). We briefly

• starting from succinimide (Scheme 3). Through a simple reaction in toluene at 80 °C in the presence of Zn(OAc)2, the hemiaminal derivative 13 underwent substitution with cinnamyl alcohol, resulting in the isolation of 14 with a satisfactory yield. Under optimized reaction conditions, the photocatalytic

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• trifluoromethoxylation by nucleophilic substitution, using an excess of DNTFB as a reservoir of CF3O− [68]. Thus, by adding cyclohexene (1a) to the preformed mixture of DNTFB (2 equiv) and DMAP (1 equiv), followed by the addition of PhSeCl, only a low yield of the expected α-trifluoromethoxylated,β-phenylselenylated

• resulting from the substitution of the CF3O group by the trifluoroacetoxy group was then observed. The activation of a fluorine atom from the CF3O group by H+ could be envisaged, which would then trigger the selenium attack to release difluorophosgene and HF, thus generating an episelenonium, which would

• are difficult to synthesize by nucleophilic substitution, such as products 5a and 5b [68]. Conclusion In this work, an efficient phenylseleno trifluoromethoxylation of alkenes has been developed to readily obtain β-selenylated trifluoromethoxylated compounds. These compounds can also undergo radical

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• t-BuO2Li reagent [31], we speculated that NaClO·5H2O would similarly work for the corresponding Z-1 with retention of stereochemistry. The procedure found here was also applied to the three representative CF3-containing α,β-unsaturated esters,1h–j [42] with different substitution patterns (Scheme 2

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• synthesized from 1,1-diphenylethanol (1i) and phenyl(thiophen-2-yl)methanol (1l), respectively, in one step by this electrochemical method. Notably, synthesis of xanthene-9-carboxylic acid (2k) and dibenzocycloheptene-5-carbocylic acid 2j was conducted with excellent yield. Direct substitution of a hydroxy by

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• corresponding thiol [35][36][37][38], in the nucleophilic substitution reaction in the aromatic ring of catechol [39][40] or under electrochemical conditions [41][42][43]. An anodic activation of catechols in the presence of a thiol leads to S-functionalized catechols with triazole, triazine, pyrimidine

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

• -substitution (CO2Me, OCH2, Br) showing excellent enantioselectivity, the 3-methoxyphenyl-substituted substrate afforded the homoallylic amine in only 85% ee. The bulky 2-cyclohexylallyltrimethylsilane showed only moderate yield and enantioselectivity (55%, 76% ee). In 2022, Mancheño and co-workers [40

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

• the shortened version described in the previous paragraph (Figure 13) [112][113][114][115]. As an interesting feature, the DADPS-linker with dibromo substitution takes advantage of the naturally occurring stable isotopes 79Br and 81Br in almost stoichiometric ratio. The predictable isotopic pattern

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

• , changes in the epi-amino alkaloid core of the two-component catalytic system were investigated. Introduction of the 2’-substitution to the quinine core as in AQ-2 and AQ-4 (Scheme 2) resulted in the decrease of chirality transfer providing the product with 50% and 72% ee, respectively. A similar trend was

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• with the stability of the relevant iminoiodinane reagent, with higher yields attributed to more electron-rich sulfonamide substitution such as 2a. Relatively electron-deficient iminoiodinanes are less efficient but are also more prone to decomposition (see Supporting Information File 1, Figure S2 for