A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• takes place to some extent, we assume that a competitive reaction pathway involving the participation of cobalt-superoxo active radicals (Co–O–O•) generated by interaction of the CoNPs with O2 [15] could not be disregarded. Conclusion To conclude, we have described a new and efficient heterogeneous

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• disrotation at C2 and C3 during stereomutation in 1,1-difluorocyclopropanes [85]. An important feature in the fluorinated system was the stabilization of the intermediate 2,2-difluorotrimethylene radicals due to the conjugation of the radical centers with the σ*-orbital of C–F bond, which can be represented

• . Further applications of free radical chemistry have developed through the use of radical initiators under comparatively mild conditions to form cyclopropylmethyl radicals, which can readily release their strain by opening to give homoallyl radicals. gem-Difluorocyclopropanes, because of their

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• used in the literature [34][35]. The use of the reagent allows the radicals to form, even at very low temperature, due to its strong reactivity with oxygen. However, the disadvantage for the use of the reagent comes from the same property: Et3B is an oxygen-sensitive and pyrophoric compound even at low

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• intermediates (triplet aryl cations [28][29] or aryl radicals [30][31]). As for the former case, the intermolecular formation of a biaryl arose from the photoheterolysis of an Ar–N bond (in arene diazonium salts or their derivatives [32][33]), of an Ar–Cl bond [34][35], of an Ar–O bond (in aryl phosphates [36

• ], aryl sulfonates [36], and in aryl trifluoroethyl sulfate [37], Scheme 1a) followed by the reaction of the thus formed aryl cation with an aromatic substrate. In an alternative approach, aryl radicals may be generated under photoredox catalysis conditions (mostly from arene diazonium salts or aryl

• the presence of increasing amounts of TFE (up to 20% v/v, continuous line). Synthesis of biarenes via a) photogenerated triplet aryl cations and aryl radicals (PC = photocatalyst), b) intramolecular free radical ipso substitution, c) thermally catalyzed extrusion of CO and SO2, d) photoinduced

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• electron transfer (SET) steps photoinitiated using visible light as the energy source, often leading to the generation of radicals and subsequent reaction of these radicals with the ground-state substrates [3]. Energy transfer catalysis is another significant branch of photocatalysis, in which

• dominant. Subsequent investigations by Yu expanded the scope to acyl radicals generated from carboxylic acids 56, affording enantioenriched 1,4-carbonyls 57 in excellent yields and good enantioselectivities (21 examples, up to 90:10 er) (Scheme 7b) [40]. The quantum yield was also measured to be <1 (Φ

• iminium ions 66 can be excited directly without formation of an EDA complex (Scheme 9a) [42]. The excited state iminium ion 66* can oxidise silanes 67 via a SET process to give radical cation 67•+ and alkyl radical 66•. Loss of the TMS group generates alkyl radicals 67• that can couple with 66

Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A

• Zhishu Zeng,
• Jun Xie,
• Guangyan Luo,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194

• addition of Q[8]. When the concentration of Q[8] was 1.0 × 10−4 mol·L−1, the solubility of OA was increased 22.47-fold. The solubility curve equation was S = 0.01c + 0.0575, R2 = 0.9986. Antioxidant activity OA has strong antioxidant activity and effectively eliminates ABTS+• radicals. If the antioxidant

• activity of OA was decreased significantly by the formation of the OA@Q[8] complex, the medicinal value of OA would be seriously affected. Figure 7 shows the results for OA and OA@Q[8] scavenging of ABTS+• radicals in the range of 1–20 μmol·L−1. The IC50 values of OA and OA@Q[8] were 4.65 × 10−6 mol·L−1

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• formation of fluorine radicals. The generated alkyl radical could abstract fluorine atoms either from i) the AQN–F complex to regenerate AQN or ii) Selectfluor® to regenerate the Selectfluor® radical cation and thereby propagate a chain reaction. Following shortly after Tan’s report, Chen and co-workers

• (+)-sclareolide (C2 and C3) are remote from the lactone EWG and both form secondary radicals. Thus, the fluorination of these positions is presumably dictated by hindrance, given that the C3 position is neighbored by a gem-dimethyl group and is fluorinated to a lesser extent (22%). In both reports, the C2/C3

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• radical cyclization of allenamides have been reported by Hsung and co-workers, where the radical adds principally to the central carbon of the allene (10) [45]; and (iii) the photoredox-catalyzed addition of radicals to enamides reported by Masson [46][47][48][49], and more recently by our own laboratory

• ]. Mechanistically, the formation of the key conjugated N-acyliminum 14a from α-aminoallyl radical 41 is analogous to the photoredox initiated addition of radicals to enamides [46][48][49]. Consequently, the formation of 14a can results from a SET event between the oxidized Ir(III) [55] and the α-aminoallyl radical

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• temperature at 70 °C based on the fact that K2S2O8 thermally decomposes forming sulfate radicals (SO4·−) [29][30], which may react with the substrates to furnish such a cascade cyclization. To our delight, the anticipated product 3aa was obtained in 42% yield in DMSO/H2O (4:1) as reaction medium in one pot

• , we successfully separated a small amount of byproduct 4 which was identified by NMR spectroscopy. These experiments clearly support a phosphorus-centered radical reaction pathway. It has been reported that phosphorus-centered radicals could be generated from phosphine oxides in the presence of

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• mild heteroaromatic functionalizations. Last but not least, a HAT-type process inducing the generation of alkyl radicals via selective C–H abstraction from the aliphatic precursors may be combined with a Ni-catalyzed process, thus delivering cross-coupled products. The aim of this review is to present

• alkane products could be controlled by adjusting the acidity of the reaction media. As in the previously described examples, molecular oxygen plays a key role in the mechanism of the C–H functionalization (Figure 10). Indeed, both the photoexcited Ir-based catalyst and the superoxide radicals formed in

• activation of one substrate, and a two-electron activation by a transition-metal catalyst of the other. The main advantage of such a system is to promote highly regioselective reactions. Indeed, while radical transformations generally suffer from selectivity issues, interception of radicals by metal

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• , namely pyrrolino-tetrahydroberberines, synthesized by some of us [68], exhibited enhanced antioxidant properties in comparison to THBER against a wide variety of pathophysiologically relevant oxidants such as peroxyl radicals, ferrous ion, and hydrogen peroxide [65]. In continuation of our ongoing

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• source of hydrogen [21]. We thought that silane 1 could couple with silyl enol ethers in the presence of a photocatalyst affording fluoroalkylation products. Indeed, silyl enol ethers were found to be good acceptors of fluorinated radicals, and the resultant silyloxy-substituted radicals underwent single

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• liquid medium are capable of breaking chemical bonds, including the sonolysis of water to hydrogen and hydroxyl radicals [159]. These conditions arise from a process known as acoustic cavitation in which the expanding phase of the acoustic wave creates microscopic voids within the solution, which

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• the control reaction (Figure 3). Because the Fenton reaction catalyzed by Cu2+ was used to generate the hydroxy radicals, entrapment of Cu2+ by 1 was initially suspected as the mechanism of chemiluminescence inhibition. However, this speculation was ruled out by a titration experiment using Chrome

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• ; phenanthridines; photocatalysis; radicals; visible light; Introduction Phenanthrenes are widely investigated compounds, due to the impressive number of diverse applications involving this scaffold, ranging from medicinal chemistry [1] to materials sciences, including their use in optoelectronics [2][3] and in

• inexpensive visible light (or sunlight, when possible) irradiation [29]. In general terms, photocatalysis smoothly gives access to reactive radical intermediates [30], mainly carbon-centered [31][32][33], or nitrogen-centered radicals [34][35]. In turn, these species have been extensively employed in radical

• -bromochalcones (Scheme 3). Thus, compounds 3.1a–d underwent a one-electron reduction by the excited photocatalyst fac-Ir(ppy)3. Upon bromide anion loss, the α-keto vinyl radicals 3.2·a–d were then formed, which smoothly added onto the vicinal aromatic ring in an intramolecular fashion, affording phenanthrene

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• . Under photoirradiation, organic disulfides can be easily cleaved into free thiyl radicals (RS•) and can reversibly add to unsaturated multiple bonds to catalyze a variety of functionalization reactions under mild conditions. In photoredox catalysis reactions, an excellent electron transfer ability and

• excellent radical properties also made these thiyl radicals powerful HAT catalysts. They have increasingly been proven useful in various types of organic photoreactions, such as cyclizations, anti-Markovnikov additions, aromatic olefin carbonylations, isomerizations, etc. They are a class of green, economic

• catalytic abilities: they can be a photocatalyst, HAT catalyst, initiator, or cocatalyst in organic synthesis. The thiyl radicals (RS•) formed under illumination conditions have the unique ability of promote radical bond-forming reactions. Their ability to reversibly add to unsaturated bonds, promoting a

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• unprecedented reductive coupling of N-benzylidene-[1,1'-biphenyl]-2-amines with an aliphatic amine. The presence of a phenyl substituent in the aniline moiety of the substrate was critical for the reactivity. The reaction proceeded via radical–radical cross-coupling of α-amino radicals generated by proton

• ]. Among these diverse applications, the Rueping group has reported excellent examples of the reductive umpolung homocoupling of imines and heterocoupling with α-amino radicals for the synthesis of symmetrical and unsymmetrical vicinal diamines (Scheme 1b) [23][26]. Notably, 1,2-diamines have widespread

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• Igor B. Krylov Stanislav A. Paveliev Alexander S. Budnikov Alexander O. Terent'ev N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russia 10.3762/bjoc.16.107 Abstract N-Oxyl radicals (compounds with an N–O• fragment) represent one

• of the richest families of stable and persistent organic radicals with applications ranging from catalysis of selective oxidation processes and mechanistic studies to production of polymers, energy storage, magnetic materials design and spectroscopic studies of biological objects. Compared to other N

• -oxyl radicals, oxime radicals (or iminoxyl radicals) have been underestimated for a long time as useful intermediates for organic synthesis, despite the fact that their precursors, oximes, are extremely widespread and easily available organic compounds. Furthermore, oxime radicals are structurally

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -, nitrogen-, oxygen-, and sulfur-centered radicals, open-shell charged species, and sensitized organic compounds. Keywords: organic dyes; photocatalysis; photoredox catalysis; radicals; reactive intermediates; Review Introduction In the last decade, synthetic organic chemistry has experienced the

• reactive intermediates. After a short introduction on activation modes in photocatalysis, selected case studies where organic dyes have been exploited for generating carbon-centered radicals, charged open-shell species, and heteroatom-centered radicals will be covered. The last short section will be

• devoted to activated organic substrates generated by energy transfer. C(sp) radicals will not be discussed. To the best of our knowledge, no report on an organophotocatalyzed generation of a C(sp) species has been disclosed yet. Each presented approach will be accompanied by one selected example, which we

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• HEH were used as H donors for both the benzyl and thiyl radicals, respectively. The HEH was needed to avoid the dimerization of the thiophenol to the disulfide (Scheme 11). Fu and co-workers have demonstrated the huge versatility of rhodium porphyrins for photocatalysis. In 2015, they showed that the

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• with TEMPO (2,2,6,6-tetramethyl-1-piperidine N-oxyl) [25] and ABNO (9-azabicyclo[3.3.1]nonane N-oxyl) radicals [26]. Later reports enlarged the synthetic scope of this methodology and provided access to a wide range of synthetically useful building blocks such as substituted heterocycles, fluorinated

• Chaudhuri [11][12][13] using well-defined copper complex 7, originally reported as a GAO mimic [20][21][22], we showed that this ability could be extended to the catalytic generation of trifluoromethyl radicals (Scheme 7) [29]. The synthetic efficiency of complex 7 in trifluoromethylation was reported on a

• cycle for the C–C coupling. The coupling reaction follows a radical–anion mechanism due to the presence of electron-donating ligand 12 and this is the key feature allowing preferential binding of the phenoxyl radicals for PCET. Products arising from homo- and heterocouplings were formed with high

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• , benzaldehyde (8) has also been studied for the ability to carry out HAT processes. In 1975, Obi and co-worker studied the photochemistry of excited benzaldehyde (9) with the use of electron paramagnetic resonance (EPR) [20]. They detected that the generated radicals from this process were the α-hydroxybenzyl

• when they were alone present in an aqueous solution, they tended to form hydrates 45 with water via hydrogen bonding. The hydrogen bonding increased the energy levels of the excited states of 45, permitting the formation of radicals after UV light absorption [48]. These radicals either dissociated via

• Norrish type I reactions, forming two radicals, 47 and 48 (reaction (1) in Scheme 12), or abstracted a hydrogen atom from a ketone/aldehyde monomer, forming a monomeric radical and an alcohol radical 49 (reaction (2) in Scheme 12). The excited state of the hydrates 45 and 46, in an aqueous solution may

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• functionalization. These salts are known since the late 1970s [30], but only in the last few years they have found application in a wide variety of radical processes, initiated by a single-electron reduction of the pyridinium salts, and subsequent generation of alkyl radicals [31][32][33][34]. Among these

• , electrophilic alkyl radicals were used in several transformations, such as electrophilic cross couplings under nickel catalysis, either with boronic acids [35] or different (aryl)halides [36][37][38]. Furthermore, visible light-promoted uncatalyzed electron transfer via the formation of electron donor–acceptor

• (EDA) complexes [39] was established between Hantzsch esters and pyridinium salts generating radicals, which were coupled with several substrates [40]. Later, methods without sacrificial reductant were also established, forming an EDA complex between the used substrates. Examples of this strategy are