(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

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• Kazuhiro Okamoto Naoki Shida Mahito Atobe Graduate School of Engineering, Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501, Japan 10.3762/bjoc.20.27 Abstract Electrochemically generated amidyl radical species produced distinct inter- or intramolecular

• 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as an additive. These results provide fundamental insights for the design of PCET-based redox reaction systems under electrochemical conditions. Keywords: amidyl radical; cyclic voltammetry; electrosynthesis; hydroamination; proton coupled electron transfer

• ; Introduction Proton-coupled electron transfer (PCET) enables the generation of various radical species under ambient conditions (Figure 1, top) [1]. In PCET processes, hydrogen bond formation between weak bases and acidic X–H bonds (X = N, O, C) is a key step, which is followed by concerted proton- and

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• indicated that both the acylamino and quinoline N motifs played a significant role. On the other hand, the stoichiometric amount of free radical inhibitors, including TEMPO and BHT, could not comprehensively suppress the reaction. Based on these experimental results and previous works [30][31][32], a

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• perpendicular to that of the aniline moiety. The calculations indicated the presence of accessible S1/S0 CIs. In the lowest-energy S1/S0 CI geometry, the aniline moiety exhibited a pronounced quinoidal character and the carbon atom directly linked to the butadiene moiety exhibited a conspicuous radical nature

• -band bleaching and increased absorption within the 500–700 nm range, an increase in the absorption intensity at 1,021 nm, corresponding to the characteristics of the C60 radical anion, was observed initially (20 ps), indicating the formation of the DEA•+–C60•− CS state. Furthermore, an increase in the

• intensity at 890 nm, indicating the emergence of 1C60* state with a lifetime of 115 ps, was accompanied by a subsequent increase in the absorption intensity at 1,021 nm, corresponding to the formation of the C60 radical anion. The lifetimes of the charge separation and charge recombination events were

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• radicals. This method allows the efficient synthesis of various indole derivatives without the need of photocatalysts or transition-metal catalysts. Mechanism experiments indicate that the process involves a radical chain process initiated by the homolysis of Umemoto's reagent. This straightforward method

• enables a rapid access to heterocycles containing a trifluoromethyl group. Keywords: cascade reaction; indole derivatives; photocatalysis; radical chain process; trifluoromethylation; Introduction Dihydropyrido[1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical

• ], Friedel–Crafts acylation [12], radical cascade reactions [2][13], and photoinduced radical cyclizations [14][15][16][17]. However, these methods often suffer from drawbacks such as harsh reaction conditions and the requirement of transition-metal catalysts. Although photocatalyzed cyclization reactions

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• ). To clarify whether the mechanism of the DNA photodamage proceeds through the formation of radicals, experiments with commmonly employed radical scavengers were conducted (Table 3, Supporting Information File 1, Figure S17). In the presence of hydroxyl-radical scavengers DMSO, t-BuOH, and 2-propanol

• hydroxyl radicals [79] or interfere with the DNA damage by alternative pathways [80]. In any case, the significant decrease of DNA damage in the presence of the radical scavengers indicated the formation and direct or indirect participation of carbon radicals and hydroxyl radicals in the photoinduced DNA

• Information File 1, Figure S18A). In the presence of NaN3 (2.5 × 10−5 M), which is a known radical scavenger for singlet oxygen [82], a strand cleavage of 25% occurred, whereas 38% cleavage was observed in the absence of NaN3. Nevertheless, a larger access of the scavenger (2.5 × 10−4 M) resulted in a

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• and reversible process named phase 1. We find that the barriers for the radical cation mechanism are significantly lower than those found for the neutral pathway. The peapod is mainly providing one-dimensional confinement for the reaction to take place in a more efficient way. Car–Parrinello

• the reaction either via singlet excitation or via radical cation formation (Scheme 1). Estimation of the activation barrier for the [2 + 2] cycloaddition when the nanotube acts as a sensitizer is 33.5 ± 6.8 kJ mol−1. This value agrees with computational predictions for the reaction via an excited

• can also be activated through the formation of C60+• radical cation [3][9]. This mechanistic proposal for phase 1, which to our knowledge has not yet been explored in detail inside a carbon nanotube, is analyzed here and compared to the non-activated C60 dimerization. Finally, some intermediates for

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• Tetrathiafulvalene (TTF, Figure 1) is a redox-active molecule that has been widely explored in materials chemistry and supramolecular chemistry [1][2][3][4][5][6][7][8]. TTF reversibly undergoes two sequential one-electron oxidations, generating first a radical cation (TTF+•) and subsequently a dication (TTF2

• rate: 0.1 V/s. All potentials are depicted against the Fc/Fc+ redox couple. Radical anion (left), dianion (middle), and radical cation (right) of compound 23; the radical anion has a 14πz-aromatic ring (highlighted in blue; only counting 2π-electrons of each triple bond, here defined as those in πz

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• and 401 nt long synthetic ssODNs, and functional in biological systems. Discussion For ODN purification using CBP, one major concern has been the damage of the ODN under the radical acrylamide polymerization conditions. Although some work has been done to prove that this is unlikely [22][23][24][25

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• potentials of the halides that can be reduced in this way, quantum-chemical calculations, and steady-state and transient absorption spectroscopy suggest that UV irradiation accelerates the reactions via cleavage of the dimers to the corresponding radical monomers. Keywords: dehalogenation; n-dopant

• ; reduction; reductive dimerization; Introduction Reductive dehalogenation reactions of organic halides can be used in organic synthesis as a means of generating carbon-centered radical or anion intermediates and could have relevance to the treatment of waste halogenated polymers. While such reactions can be

• to any detectable BnSiMe3, thus supporting a radical dimerization pathway (see Supporting Information File 1, Table S3). As in the case of sp2 R–X systems, only small extents of dehalogenation for R = aryl are observed in the absence of reductants. For the more easily reduced aryl halides (3a–c

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• reaction is believed to occur via electron transfer, followed by the radical coupling of La@C2v-C82 and benzyl radicals, rather than by bimolecular nucleophilic substitution reaction of La@C2v-C82 anion with 1. Keywords: electron transfer; metallofullerene; radical; reduction; Introduction Fullerenes

• derivatives followed by the radical coupling reaction is more plausible for the formation of the corresponding adducts rather than the SN2 reaction mechanism of the La@C2v-C82 anion with benzyl bromide derivatives. Conclusion The reaction of La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C

• were strongly affected by the addition sites. Based on theoretical studies and considering the identified addition sites, a plausible reaction mechanism for the reaction is the electron transfer from La@C2v-C82 anion to benzyl bromide, followed by radical coupling. This demonstrates that one-electron

Thienothiophene-based organic light-emitting diode: synthesis, photophysical properties and application

• Recep Isci and
• Turan Ozturk

Beilstein J. Org. Chem. 2023, 19, 1849–1857, doi:10.3762/bjoc.19.137

• adapted with permission of Institution of Chemical Engineers (IChemE) and The Royal Society of Chemistry from [38] (“Cationic and radical polymerization using a boron–thienothiophene–triphenylamine based D-π-A type photosensitizer under white LED irradiation”) by A. Suerkan et al., Mol. Syst. Des. Eng