A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

•  1b). Alternatively, the oxidation of α-C–H of active methylene ketones generate α-carbon-centered radicals, thus providing another way to obtain thiazoles. Recently, Sun et al. reported a tert-butyl hydroperoxide/azodiisobutyronitrile-mediated synthesis of 2-aminothiazoles from active methylene

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• -known mechanophore that generates diarylacetonitrile radicals under force. Hence, when TASN derivative 8, bearing diarylurea moieties, was ball milled, the corresponding radical 9 was detected by electron paramagnetic resonance (EPR) spectroscopy. Similar treatment proved that 6 was 28 times less prone

• to generate radicals (Scheme 3) [67]. The difference in the C–C bond scission between 6 and 8 was explained based on the ability of diarylurea moieties in 8 to form strong self-assemblies through hydrogen bonding. In the solid state, this enabled the transduction of mechanical force to the

• mechanophores. Moreover, it was demonstrated that the hydrogen bonds of the diarylurea linkages also acted as supporting units to maintain the activated mechanophores (radicals) for a longer time [67]. Overall, this new strategy, which harnesses the power of noncovalent interactions by ball milling [68][69][70

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• , entry 2). On the other hand, the isolated yield of 3 was decreased by the addition of H2O (Table 2, entries 3 and 4). This is probably because the addition of H2O promoted the generation of hydroxyl radicals, and a decomposition reaction became dominant. These results indicated that the oxygen source is

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• host against oxidative radicals generated by UV irradiation [25][32]. To verify the antioxidative effect of the isoflavone dimers, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-based antioxidant activity was performed [33]. The results showed that while 2 and 3 had an activity roughly

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• at the β-position had a significant impact on the reaction. In general, tertiary radicals (or cations) are more stable than secondary ones and therefore, the additional methyl group seems to have a strong steric effect (Figure 3). If so, tying up the two methyl groups as a cyclopropane ring may

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• )difluoromethyl group (ArSCF2) have potential biological applications such as anti-HIV-1 reverse transcriptase inhibitors and agrochemical applications [3][4]. Reurakul and Pohmakotr et al. carried out the reaction of PhSCF2Br with SmI2 in THF/iPrOH to generate PhSCF2 radicals followed by trapping with various

• radicals such as n-perfluoropropyl radical have high reactivity to electron-rich olefins such as α-methylstyrene and styrene [26]. In fact, our cathodically generated reactive species also reacted with α-methylstyrene. However, electron-rich dihydrofuran did not provide any radical adduct at all (Table 1

• often employed. Médebielle et al. successfully carried out the cathodic reduction of ArCF2X and RCOCF2X with nitrobenzene as a mediator to generate the corresponding difluoromethyl radicals selectively, and they applied this electrocatalytic system to the synthesis of various heterocyclic compounds

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• )benzene (5c), and S-shaped double helicenes DH-1–3 is shown in Scheme 1. The double oxidative photocyclization of 5a–c is the key step in the synthesis of DH-1–3 because oxidative photocyclization induces double radicals on a double bond, which led to the C=C bond rotation along the resulting single C

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• solubility of this class of molecules, perfluoroalkyl iodides have a tendency to be weakly soluble in common organic solvents (i.e., ethyl acetate and methanol) rendering their application troublesome [9]. Moreover, the homolysis of the perfluoroalkyl iodide produces iodine radicals that can result in stray

• halogenation reactions or oxidation. For these reasons, it would be ideal to develop an efficient methodology that allows for the generation of perfluoroalkyl radicals in a mild, redox- and pH-neutral manner, without the assistance of external photocatalysts, heavy metal catalysts, or further additives. Thus

• , trifluoromethyl radicals and its longer-chain analogues, share a common electrophilic character and a stabilizing stereoelectronic effect [14], we envisioned that the “dummy group” methodology could be translated into the formation of sought after perfluoroalkyl radicals (Scheme 1). In this work, we report the

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• , natural and (semi)synthetic endoperoxides with wide structural diversity show antimalarial activity against Plasmodium falciparum malaria. In this case, the reductive activation of the endoperoxide ring with the homolytic cleavage of the O–O bond leads to the generation of carbon-centered free radicals

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• •−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and hydroperoxyl radical (•OOH) (Figure 3) [35]. Additionally, the menadione semiquinone radical can participate in another redox cycle, such as, the Fenton reaction, also resulting in the production of hydroxyl and hydroperoxyl radicals (Figure 3) [39][40

• dichloromethane and tert-butyl hydroperoxide at 80 °C (Table 2, entry 12). Methylation of 1,4-naphthoquinone Another route to prepare menadione (10) involves the methylation of 1,4-naphthoquinone. Because of their electron-deficient character, quinones are highly reactive with nucleophilic radicals [75]. The most

• useful alkylation approach is the Kochi–Anderson method [76] (or also known as Jacobsen–Torssell method [77][78]), via oxidative decarboxylation, where the quinone reacts with a carboxylic acid in the presence of silver(I) nitrate and ammonium or potassium peroxydisulfate. Nucleophilic free radicals are

High-speed C–H chlorination of ethylene carbonate using a new photoflow setup

• Takayoshi Kasakado,
• Takahide Fukuyama,
• Tomohiro Nakagawa,
• Shinji Taguchi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16

• homolysis of the Cl–Cl bond to generate chlorine radicals. In a subsequent step, a SH2 reaction by chlorine radicals at C–H bonds generates alkyl radicals and HCl. The second SH2 reaction between alkyl radicals and molecular chlorine then occurs to give the C–H chlorinated product and a chlorine radical

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• electrons through a redox cycle promoted by the 1,2- or 1,4-naphthoquinone system. In this cycle, transient reactive oxygen (ROS) and nitrogen (RNS) species are formed as free radicals, peroxides, superoxide anions, radical anions, or dianions. These species generated inside cells accelerate hypoxia and

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• strategy for aldehyde C–H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the

• functionalization using DABCO as a hydrogen atom abstractor in a photocatalytic strategy for synthetic purposes. In this context, our work aims to broaden the scope of DABCO-promoted photocatalytic C–H functionalization including formyl bonds of aldehydes as substrates (Figure 2e). The acyl radicals generated

• conditions were established, we investigated the generality of the aryl bromide scope using isovaleraldehyde (1) as source of acyl radicals. Scheme 1 shows that electron-rich and non-substituted aryl bromides seemed to give only moderate isolated yields (4–6, 39–53%), but electron-withdrawing substituted

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• . Similar to their previous report, primary and secondary alkyl halides were prone to undergoing direct cross-coupling rather than radical addition across the π-system. Consistent with the proposed mechanism, perfluorinated n-alkyl radicals performed well, suggesting ease of Giese addition is crucial [67

• radical 28 (Scheme 5). Regioselective Giese addition to the π-system 21 would generate the transient 2° alkyl radical 29. Due to the high energetic barrier associated with direct cross-coupling between sterically hindered 3° alkyl radicals and aryliron complexes, it is assumed the persistent aryliron

• radicals [98]. Concurrently, Guo and co-workers reported a similar approach towards the synthesis of dihydrofurans 101 through the sequential radical addition/cyclization of inactivated C(sp3)−H bonds 100 with olefinic dicarbonyl species 99 (Scheme 19) [99]. Both accounts found the reaction was shut down

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• damage caused by oxidative stress, especially by eliminating reactive oxygen species (ROS) such as hydroxyl radicals (•OH), superoxide anions (O2•‒), and singlet oxygen (1O2) [3][22][23]. Therefore, research in recent years has focused on new compounds obtained from natural sources or by synthetic

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• give imines, iminium salts, aldehydes and other, in some cases dimeric products [49]. Here, oxidation of the benzylic amino moiety should lead either to iminium ions (or N-acyl iminium ions) 4a as strong electrophiles or to stabilized radicals 4b which could undergo cyclization to give the fluorenone

• unsuccessful, fluorenone (3) was not formed under either of these conditions, suggesting the involvement of radicals in the cyclization reaction rather than an SEAr mechanism as proposed in Scheme 3. A more detailed investigation might be required to fully understand the mechanism of this oxidative benzylamine

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• , 18 (Scheme 10 and Scheme 11). Based on previous mechanistic studies [41], the authors found that the photoexcited ligand–CuI−amido species transferred electrons to alkyl halides to produce alkyl radicals, which reacted with alkenes and amines to generate the three-component coupling products. In the

• alkyne (Scheme 18). Under visible-light irradiation, disulfides are easy transformed to thiyl radicals via the homolytic cleavage of the S–S bond [79]. In 2020, Anandhan and co-workers [80] explored the C(sp)–S coupling of terminal alkynes with 2-aminothiophenol dimer 38 as a radical precursor. Under

• photoexcitation the CuI acetylide A undergoes a SET process to form the CuII phenylacetylide species B and a superoxide radical anion. In parallel, under irradiation the homolytic S–S-bond cleavage in 2-aminothiophenol dimer 38 forms thiol radicals 40. The nucleophilic addition of the amino group in radical 40 to

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• electron donor iminyl radical. In fact, iminyl radicals have been identified and studied by EPR spectroscopy in a number of related processes involving oxime derivatives [14]. As an example utilizing substrate 14d, intermediates such as the iminyl radical 17a and the ring closed intermediate 17b (Figure 3

• radicals. Two possible mechanistic routes and intermediates in the synthesis of phenanthridines. Previous unexpected synthesis of the phenanthridine framework. Synthesis of biaryl benzaldehydes. Synthesis of biaryl oximes. Synthesis of phenanthridines. Reagents and conditions (i) UV irradiation (450 W

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• salts are generated in situ and converted to radicals through irradiation with visible light. Reaction products precipitate from the solvent, eliminating the need for purification and thus providing a novel green method for the synthesis of versatile bis-electrophiles. Keywords: benzoquinone; diazonium

• investigating the influence of the catalyst, we discovered that the reaction proceeded smoothly in the absence of eosin Y, implying an autocatalytic or self-promoting system. A similar process has recently been described by Wu et al. [40], in the arylation of BODIPYs [41][42][43], where radicals are formed

• on our findings. The authors reported the arylation of different substrates by irradiating aryldiazonium salts in methanol with blue light in the absence of a catalyst. Radicals are proclaimed to be generated through excitation of an intermediate aryl cation formed in the reaction. Eager to

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• generation of nucleophilic α-amino radicals 2-IV via a photoredox-mediated HAT process. At the same time, the in situ generated nickel(0) species 2-V by a SET process would undergo oxidative addition into aryl bromide 3, resulting in the electrophilic nickel(II)–aryl intermediate 2-VI. The rapid coupling of

• cycle involving the generation of methyl radicals via β-scission of a tertiary radical which in turn was generated from trimethyl orthoformate by a photogenerated chlorine radical-mediated HAT process (Figure 14) [92]. Recently, Stahl devised a photoredox nickel-catalyzed methylation of benzylic and α

• alkanes 16, alkenes 92, and aryl bromides 3 (Scheme 48) [140]. Here, TBADT enables the generation of alkyl radicals from various alkane substrates via a HAT process under near-ultraviolet light irradiation. Both cyclic and linear alkanes were found to be suitable under the reaction conditions. Linear

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• better stabilization of cation radicals, di-, and polycations by the unique dipolar nature of azulene, and in the case of iodine doping, it was attributed to the strengthened spin–spin interaction arising due to a high radical concentration. Recently, it was also established that the water-dispersible

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• ) to generate initiating radicals. In this work, a large series of 17 NIR dyes mainly based on a well-established cyanine scaffold is proposed (Scheme 1). Markedly, eleven of them were never synthesized before. These NIR dyes are studied in three-component systems in combination with an iodonium salt

• governing the formation of initiating radicals. The slightly lower reactivity of NPG vs DABA can probably be ascribed to a lower production of initiating radicals in this case, rendering the associated PIS slightly less efficient to overcome the oxygen inhibition. This behavior has already been observed in

• polymerization is much more efficient when borate is used as the counter anion with both a higher polymerization rate and FC. The results show that the formation of initiating radicals can be related to the decomposition of the borate moiety. This can be explained by the fact that the borate counter ion can act

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• anilines afforded α-aminoalkyl radicals that could be coupled with a wide range of electrophilic partners to afford the products in moderate to good yields. The new reaction was also used in the first step of the total synthesis of a caspase-3 inhibitor (90), and mechanistic investigations showed that O2

• behaves as a terminal oxidant to form α-aminoalkyl radicals, whereas the formation of an Fe-peroxo species in the catalytic cycle was confirmed using a combination of EPR and ESI mass spectrometry experiments (Scheme 31D). One-pot processes for the synthesis of benzo[b]furans from aryl- or alkylketones

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• is also oxidized to Mn(III)/L–N3. Azide radical addition to Mn(II)/L to form Mn(III)/L–N3 was considered as a possible route. Concurrently, the photocatalyst is irradiated by blue LED light to induce hydrogen atom transfer (HAT) at the C–H bond of substrate 12, generating alkyl radicals and enabling