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

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