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

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• benzylic alcohol selectively to the aldehyde or ketone is still desirable. Recently, cerium photocatalysis was introduced as a robust alternative to generate oxygen or carbon-centered radicals under mild reaction conditions [57][58][59][60][61][62][63][64]. CeCl3 reacts via ligand-to-metal charge transfer

• generating oxygen-centered radicals, that lead to carbon-centered radicals through intra/intermolecular hydrogen atom transfer (HAT) processes, radical decarboxylative or radical deformylation [57][58][59]. In continuation of our research interest on visible-light-driven cerium photocatalysis [59][65], we

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• cycloisomerizations initiated by the MHAT process in all-carbon quaternary synthesis The synthetic potential of carbon-centered radicals to construct new C(sp3)–C(sp3) bonds was considerably expanded by the development of MHAT strategies involving olefins as substrates. The regioselective transfer of the hydrogen

• (Scheme 17B). The proposed mechanism involves the formation of a cobalt hydride species that, upon transfer of a hydrogen atom to 32, generates a geminate radical pair containing a Co(II) species and a benzylic radical. The escape from the radical cage then generates the corresponding free radicals, which

• on the solvent radical cage efficiency and, consequently, on the concentration and “life-time” of the alkyl free radicals generated after the solvent cage collapse. In the latter case, the alkyl radical needed more time to cyclize before engaging in another solvent cage. After a β–H abstraction, it

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• observation was that the presence of radical traps, such as 4-hydroxy-substituted TEMPO, was detrimental for the reaction, which evidently involved free radicals. Anaerobic conditions (degassing with argon) inhibited the reaction, which could be restarted when oxygen was bubbled into the solution. This

• observation showed that oxygen, although not involved in the stoichiometry of the reaction, was critical. The alcohol corresponding to the alkyl residue was detected as a side product and became the main reaction product with substrates that generated stabilized radicals such as benzyl radicals. The formation

• ⋅mol−1) and favored over abstraction by a hydroperoxy radical, which would be only exothermic by 2 kcal⋅mol−1. The exothermicity of the hydrogen abstraction reaction is reduced with stabilized radicals, which have weaker C–H bonding. In this case, trapping by dissolved oxygen competes, generating a

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• the generation of cyanomethyl radicals from readily available acetonitrile has not been reported yet. Herein, we disclose a CN-K-catalyzed cyanomethylarylation of both unactivated and activated alkenes with acetonitrile utilizing readily available alkyl N-hydroxyphthalimide (NHPI) esters as the

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• high temperatures in the absence of a catalyst (Scheme 1a) [14][15][16]. However, these reactions do not exhibit any selectivity due to the indiscriminate attack of bromine radicals on the C–H bonds in the substrate, which leads to the formation of a mixture of halogenated products. Electrophilic and

• (sp3)–H bromination reaction. The proposed reaction mechanism is shown in Scheme 5, which involves the following steps. (1) The reaction between NBS and TMSN3 generates bromine azide via the elimination of N-(trimethylsilyl)succinimide [52][53]; (2) bromine and azide radicals are then formed via

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• Innovation, Faculty of Agriculture, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan 10.3762/bjoc.17.72 Abstract The homolytic cleavage of the PV(O)–PIII bond in tetraphenyldiphosphine monoxide simultaneously provides both pentavalent and trivalent phosphorus-centered radicals with different

• was produced in 28% yield (Table 1, entry 2). However, 3a was obtained only in trace amounts upon irradiation with a tungsten lamp [51] (Table 1, entry 3). These results indicate that Ph2P• [52][53][54][55] and/or Ph2P(O)• [56][57][58][59] radicals were generated by the irradiation with light in the

• near-UV region. When benzene was used instead of CDCl3 under xenon lamp irradiation, the reaction did not proceed because 1 was less soluble in benzene than CDCl3 (Table 1, entry 4). The radical initiator, V-40, was found to be an appropriate initiator for the generation of phosphorus-centered radicals

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• the excited state, causing an electron transfer to give radicals and to initiate subsequent reactions. Besides light as an external energy source, reactions involving the participation of EDA complexes are mild, obviating transition metal catalysts or photosensitizers in the majority of cases and are

• spectroscopy shows that phosphono radicals could proceed throughout the reaction. A halogen bond (XB) is a noncovalent interaction formed between a halogen atom and a neutral or negatively charged Lewis base. It is a kind of weak intermolecular interaction analogous to a hydrogen bond and basically can be

• aminosulfonylation, employing blue light as irradiation source (Scheme 5). It has to be said that nitrogen radicals played a coordinating role in the sulfonation step. Additionally, to verify the applicability of this approach, 1H-benzo[d][1,2]thiazine 2,2-dioxides have been prepared successfully. A possible

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• ROESY investigations (see Supporting Information File 1). This corresponds to the previously reported data for N-benzylacetamides [82]. It can be assumed that the amide enolates after the Brook rearrangement and the α-amide radicals (4S,S)-19i–k and (4R,S)-19i, respectively, resulting after SET

• and the sterically more demanding phenyl ring of the 1-arylethyl group in (4R,S)-19i at the β-face shielding it in both radicals for the approach of TEMPO (3), but significantly more effectively in (4R,S)-19i (Scheme 7). The α-face is in contrast much less crowded and allows smooth radical coupling

• cyclized radicals 22 couple subsequently with TEMPO providing lactams 12a–k after deprotection of the TMS groups. The cyclized tertiary alkoxyamines (R3 = Me) are known to be thermally labile [89][90][91][92] and consequently 4-isopropenylpyrrolidones 12g,k are isolated as the exclusive products. The

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• scission of C–C bonds into radicals, which leads to a complex mixture of olefinic and cross-linked compounds [143]. In a few cases, good selectivity to a liquid fraction was achieved. For instance, nanostructured BaTiO3 doped with Pb provided a mixture of liquid products, which includes alkanes (73.4