Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• Kosuke Yamamoto Kazuhisa Arita Masami Kuriyama Osamu Onomura Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan 10.3762/bjoc.20.116 Abstract The radical hydroarylation of alkenes is an efficient strategy for accessing linear alkylarenes with

• that a reductive radical-polar crossover pathway is likely to be involved in this transformation. Keywords: aryl halides; C–C bond formation; electroreduction; radicals; visible light; Introduction Alkene hydroarylation is an attractive method for the construction of alkylarenes, which serve as

• a hydride donor [5][6][7][8]. On the other hand, aryl radical-involved hydroarylation would be a promising alternative for the synthesis of alkylarenes with high anti-Markovnikov selectivity [9][10]. Aryl halides have received increased attention as ideal radical precursors because of their

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical

• 0.34, is essentially non-reactive under our conditions. Cyanopyridine- and sulfinate-derived radicals are produced in equal concentrations in the catalytic cycle, suggesting that radical coupling is indeed the final reaction step to give the stable sulfonylation/arylation product. The triplet of Aza-H

• potentials of Aza-H and the substrates and initial steady-state fluorescence quenching experiments (Scheme 1, left), but detailed mechanistic insights and direct evidence of the transient radical ions could not be obtained yet [45]. Figure 1A illustrates the absorption and emission spectra of Aza-H in MeCN

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• similar mechanism may be assumed for the formation of the other oxamides 9 and 13. Mechanism for the formation of 2,5-bis((2-methoxyphenyl)amino)cyclohexa-2,5-diene-1,4-dione (10) Generally, formation of polyaniline occurs through a radical mechanism. Such a radical mechanism is relevant for the formation

• of quinones having exceptional radical-stabilizing abilities. The best example in nature is the radical pathway in the catechol oxidation process [56][57][58]. The structure of o-anisidine resembles catechol as it has two adjacent electron-donating functions (NH2 and OMe). For o-anisidine, the amine

• radical resulting from reaction of o-anisidine with SeO2 is stabilized by resonance (Scheme 7). It combines with the hydroxyl radical and undergoes subsequent oxidation to give 2-methoxycyclohexa-2,5-diene-1,4-dione. This iminoquinone upon hydrolysis gives 2-methoxycyclohexa-2,5-diene-1,4-dione, and the

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• -dependent reactions of AlpJ-family oxygenases. Furthermore, the AlpJ- and JadG-catalyzed reactions of CR1 could be quenched by superoxide dismutase, supporting a catalytic mechanism wherein the substrate CR1 reductively activates molecular oxygen, generating a substrate radical and the superoxide anion O2

• bond cleavage, ring opening, and rearrangement reactions, yielding the respective products. Furthermore, the reactions of 8 catalyzed by JadG and AlpJ could be quenched by superoxide dismutase (SOD), supporting a catalytic mechanism involving the generation of a substrate radical and the superoxide

• substrates to activate molecular oxygen, leading to the generation of a substrate radical and the superoxide anion O2•− [29][33][37]. The well-established superoxide trapping agent superoxide dismutase (SOD) has demonstrated significant inhibition of the NMO-catalyzed monooxygenation reaction [29]. To probe

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• perpendicularly. Unfortunately, the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry of 3 afforded no molecular ion peak expected for adducts derived from Dip2Si and C60 while a base peak at m/z 720 due to C60 was observed probably because of the low stability of radical

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• control studies with Hg and TEMPO indicated that the reactions were homogeneous and did not proceed through a radical pathway. Synthesis of heterocycles via C–C and C–N bond formation In 2016, Beller and co-workers reported an intramolecular cyclization using 2-(2-aminophenyl)ethanol for the synthesis of

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• considering the most atom-economical options, namely chlorine and bromine, the latter typically exhibits some advantages over the former. These include: (i) better regioselectivity in radical processes, attributed to the lower bond enthalpy of H–Br (88 kcal/mol) compared to H–Cl (103 kcal/mol) [17], (ii

• functionalisation on the aromatic ring when used in the dark [20]. A classic example is the bromination of toluene with molecular bromine. When the system is exposed to light (right side of Figure 1), a radical mechanism is initiated by Br• coming from Br2 homolysis. Propagation involves the reversible abstraction

• of a benzylic hydrogen atom from the substrate by Br•, to give HBr and a structure-stabilised carbon-centred radical, which may react with Br2 to give the brominated product, thus regenerating Br• that is able to sustain the chain process. In the absence of light (left side of Figure 1), the reaction

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• photoinitiated radical polymerizations [7][8]. Consequently, there exists a growing interest in the development of more convenient synthetic routes for these compounds, facilitating the creation of structurally novel diaryliodonium(III) salts. The counterions of diaryliodonium(III) salts play a crucial role in

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• part in the arbitrarily shaped edges results in the emergence of radical π-electron states called “edge states”, which are spatially localized at the edge site. The edge states appear at the Dirac point at which two linear conduction (anti-bonding) π*- and valence (bonding) π-bands touch each other in

• the electronic energy bands of graphene. Since the Fermi level is located at the Dirac point for neutral nanographene, edge states are half-filled like singly occupied molecular orbitals (SOMO) of radical states. Namely, nanographene sheets become magnetic and chemically active due to the edge states

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• interesting method toward indole-3-yl aryl ketones was reported by Zhang et al. Considering the ability of the aryldiazonium salts to act as aryl radical source, in presence of the suitable metal catalyst or taking advantage of photocatalysis, they decided to perform a direct carbonylation of indoles with

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• itself accessible in good yields from allyl chloride 1 using a route based on that reported by Schlüter [28]. Bifunctional 1,2-BCP (±)-4 bearing orthogonally protected alcohol functionalities was obtained from 3a through a three-step sequence of strain-release radical ring-opening with iodochloromethane

• (±)-30. In a related strategy, Procter and co-workers prepared 1,2-BCHs (±)-33a–e from BCBs 32 via a SmI2-catalysed radical relay alkene insertion (Scheme 3C) [35]. This approach relied on single-electron reduction of the ketone moiety and ring-expansion from the ketyl radical anion. Electron-deficient

• haloalkylation with alkyl iodides (Scheme 14A) [27][47]. This reaction can be performed either under photoredox catalysis conditions or without the need for an initiator, depending on the used alkyl iodide. For selected examples, the radical initiator Et3B could also be used. Activation by photoredox catalysis

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• amount of the C-9 epimerization product 11 might be explained by a competing radical oxidation of the organoborane intermediate IM-16 by oxygen when the oxidation step is opened to air [32][33]. On the other hand, an alternative mechanism for the formation of 11 involving the oxidation of the 9-epi-IM-16

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• -positions to the ester group were all well-tolerated (Table 3). To gain further insights into the reaction mechanism, we conducted control experiments. Given the utility of diaryliodonium salts in radical chemistry, we introduced 2 equivalents of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2 equivalents

• of butylated hydroxytoluene (BHT) into the template reaction. Remarkably, we observed that the desired product was not formed, suggesting a radical pathway. Subsequently, we investigated the bond-formation sequence in the benzocyclization reaction. A possible intermediate of 3al’ was prepared and

• tested in the reaction under the standard conditions, however, product 3aa was not obtained. Based on the literature known results and the experimental evidences [35][36], we proposed a plausible reaction mechanism (Scheme 2b). The reaction started with the formation of radical intermediate A from

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations. Keywords: addition reactions; alkenes; alkyl chlorides; hydrochlorination; Markovnikov; Introduction The hydrochlorination of alkenes dates back to its

• on metal-catalyzed radical hydrochlorinations [11] and anti-Markovnikov hydrochlorination reactions, highlighting the ongoing challenges in achieving a simple addition of HCl across a simple double bond. During our literature review for this article, we identified two other significant reviews

• simultaneous mechanism [15][16][17][18][19]. 2) Radical hydrochlorinations: These reactions involve the in situ formation of a carbon-centered radical, which is then trapped by an appropriate chlorine source. 3) anti-Markovnikov products: This category describes a new field in hydrochlorination reactions

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• discovery and development of the synthesis of homopropargylic azides by the azido-alkynylation of alkenes. Initially, a strategy involving SOMOphilic alkynes was adopted, but only resulted in a 29% yield of the desired product. By switching to a radical-polar crossover approach and after optimization, a

• , greatly increasing the molecular complexity of the starting substrate. Using radical chemistry would lead to a regioselective addition of azide radicals to the alkene, forming selectively the most stabilized C-centered radical. A prominent method for the generation of azide radicals relies on hypervalent

• iodine reagents [15][16]. Azidobenziodoxolone, also known as Zhdankin reagent, has often been used under thermal or photochemical conditions to generate the desired azide radical in a controlled fashion. However, recent safety issues arising from the shock and impact sensitivity of the compound led to

Organic electron transport materials

• Joseph Cameron and
• Peter J. Skabara

Beilstein J. Org. Chem. 2024, 20, 672–674, doi:10.3762/bjoc.20.60

• react with acceptors to produce reducing radical species, capable of reducing organic electron transport materials with a low electron affinity [4][5]. It is not only in modifying the molecular structure to improve the electron accepting ability that there is innovation in new organic electron transport

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε

• multicomponent reaction protocol. Keywords: carboamination; diazo chemistry; palladium catalysis; radical-polar crossover; three-component reaction; Introduction Since the discovery of the existence of non-canonical amino acids (AAs) in organisms, such structural motifs have attracted considerable attention

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• molecular species withdraws a hydrogen atom, and the generated radical induces various reactions such as hydroxylation, unsaturation, epoxidation, halogenation, endoperoxidation, and C–C bond reconstruction, leading to the formation of diverse chemical structures [22][26][27][28][29][30][31]. Structure

• berkeleydione (28), respectively (Figure 5) [32][33]. In the initial reaction, AusE abstracts H-2 of 24, while PrhA abstracts H-5 of 24. PrhA and AusE form a double bond to yield preaustinoid A2 (25) and berkeleyone B (26), respectively (Figure 5). AusE abstracts H-5 of 25, forming a radical that initiates a

• reactions, the terpenoid skeleton undergoes significant structural changes due to radical formation through oxidase-induced hydrogen atom abstraction. Close examinations of the substrate complex structures of these αKG-dependent dioxygenases involved in these meroterpenoid oxidations revealed that the

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• ). Antioxidant activity of 1 was measured via the DPPH radical. 1 showed potent DPPH radical scavenging activity with an IC50 value of 5.0 μg·mL−1, which is lower than that of trolox (IC50; 7.5 μg·mL−1) (Table 2). In contrast, 1 did not show antimicrobial activity against Gram-positive and Gram-negative bacteria

• ), fungi (e.g., Aspergillus sojae and Penicillium roquefortii), and bacteria (e.g., Acinetobacter calcoaceticus, Brucella abortus, and Bacillus sp.) [15]. It is also known to be a component of some natural products, such as enterobactin, showing strong radical scavenging activity or antioxidant activity

• [16]. KR21-0001A (1) is a new analog of 2,3-DHBA connected to N-acetylcysteine (Figure 2b). 1 has a stronger antioxidant activity than trolox, which is a water-soluble analog of the free radical scavenger α-tocopherol [17][18]. 1 shows no antimicrobial activity against bacteria and fungi. Conclusion

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• complex was also formed by mixing a 1:1 mixture of radical cations of [5]- and [10]CPP, [5]CPP•+ (SbCl6−) and [10]CPP•+ (SbCl6−), respectively (Figure 1c, path C). The observed results can be explained by two reasons; one is the oxidation potentials of [10]- and [5]CPPs. In sharp contrast to linear π

• , and 3. While the extent of the CT in the current complexes is slightly greater than that in [11]CPP⊃La@C82 (7%) [39], the results are still far from being sufficient for the formation of a radical ion complex, [10]CPP•+⊃[5]CPP•+. Indeed, the structural properties, as seen from the bond length

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

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

• many applications as radical precursors. Mechanistically, NHPI esters undergo a reductive decarboxylative fragmentation to provide a substrate radical capable of engaging in diverse transformations. Their reduction via single-electron transfer (SET) can occur under thermal, photochemical, or

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• reaction classes, we discuss the utility of the NHPI esters, with an eye towards their continued development in complexity-generating transformations. Keywords: decarboxylative couplings; mechanisms; NHPI-esters; radical reactions; Introduction The historical challenges of using radicals in synthetic

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• = −1.39 V to a radical anion and then undergoes irreversible reduction at Е1/2RED2 = −1.91 V and irreversible oxidation at Е1/2OX = 0.48 V. These CV parameters are close to those recorded for triphenodioxazines [23]. The energy of the HOMO and LUMO orbitals assessed on the basis of the CV and electronic