Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• benefits of the photomechanochemical approach in the field of synthesis [77]. Specifically, they developed photomechanochemical conditions for the atom-transfer-radical addition (ATRA) of sulfonyl chlorides to alkenes, pinacol coupling of carbonyl compounds, decarboxylative acylation, and photocatalyzed [2

• reactions: A) atom-transfer-radical addition, B) pinacol coupling, C) decarboxylative alkylation, D) [2 + 2] cycloaddition. The photo in Scheme 11 was reproduced from [77] (© 2024 F. Millward et al., published by Wiley-VCH GmbH, distributed under the terms of the Creative Commons Attribution 4.0

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• transformations have been addressed by Gianetti et al. such as C(sp3)–H oxidation, intermolecular atom transfer radical addition and C(sp)–H arylation using red light and DMQA (Figure 14), hence showing the great versatility of this photocatalyst. Red-light photocatalysis in biological systems Photochemical

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• (II)–N3 complex 60. The azidyl radical 62 then reacts with N-arylenamine 57 via radical addition. Thereafter, it undergoes oxidation to form a kinetically labile vinyl azide intermediate 64. This vinyl azide intermediate 64 dissociates, yielding Cu(II) iminyl complex 65 via denitrogenation

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

• slight increase in chemical yield. Giese reaction: Radical addition on olefins with an electron-withdrawing group (EWG) followed by a HAT or SET and protonation; halogen-atom transfer: (a) tin-mediated XAT, (b) XAT initiated by a photocatalyst (PC) and mediated by boranes (B), silanes (Si) or alkylamines

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• challenges in the synthesis of [n]staffanes using excess [1.1.1]propellane (1). (Bottom) selective synthesis of [2]staffanes bearing the SF5 (2) and CF3SF4 (3) groups (this work). Computed free energy profile for the oligomerization of [1.1.1]propellane (1) following SF5 radical addition at PWPB95-D4/def2

• -QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory. Computed free energy profile for the oligomerization of [1.1.1]propellane (1) following CF3SF4 radical addition at the PWPB95-D4/def2-QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory. (A) The molecular structure of 3 at 90 K with 5 independent

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• literature, oxacepham scaffolds, the 6-membered fused bicyclic analog of clavams, were prepared from appropriately substituted unfused precursors by intramolecular C-radical addition to alkene functionalities [44]. The utilization of radical conditions has prevented the effective nucleophilic opening of the

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• radical; isocyanide; radical addition; radical cyclization; Introduction Carbon monoxide is a very important C1 resource in both synthetic and industrial chemistry and is not only capable of reacting with a variety of active species such as carbon cations, carbon anions, and carbon radicals (Figure 1

• to imidoyl units generated in situ by radical addition to isocyanides, innovative molecules with a variety of functions can be obtained. In other words, if functional groups can be prepared simultaneously with the formation of an imidoyl group, it would be an extremely useful method for the synthesis

• the combination with groups 15–17 interelement compounds would be considered effective for the generation of groups 13 and 14 heteroatom radicals. Radical addition of group 17 compounds to isocyanides If isocyanides (RNC) can undergo a radical addition of hydrogen halides (HX) and molecular halogens

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• Abstract A flow photochemical reaction system for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence was developed, which utilizes in situ-generated 2-benzopyrylium intermediates as the photoredox catalyst and electrophilic substrates. The key 2-benzopyrylium intermediates were

• subsequent photochemical radical addition [46][47][48][49][50][51][52][53][54], which affords 1H-isochromene derivatives 3 through three catalytic cycles (Scheme 1a) [55]: catalytic cycles I and II and a photoredox cycle of the photocatalyst [56][57] (see Supporting Information File 1 for the overall

• improved the yield of 3t (78%), presumably because of the retardation of the desilylation process (from B to C in Scheme 1a). Conclusion We have demonstrated a flow reaction system for a π-Lewis acidic metal-catalyzed cyclization/photochemical radical addition sequence, affording, in most cases, the 1H

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• presented. We also discuss the selectivity of the radical addition to Ni(II) norcorroles using DFT calculations. Results and Discussion Reactivity with azo radical initiators We selected 2,2'-azobis(isobutyronitrile) (AIBN) as a radical source. Ni(II) dimesitylnorcorrole 1 was treated with AIBN in refluxing

• antiaromatic character of the macrocycle changed to nonaromatic upon radical addition (see Supporting Information File 1). 1,1'-Azobis(cyclohexane-1-carbonitrile) (V-40) was also examined as a radical source. The reaction afforded 2b in 87% yield (Scheme 2). Unfortunately, other radical sources, such as

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• reactions were not described at all. Nevertheless, the radical reactions are the most powerful instrument for the preparation of new molecules with a CHF–CHF fragment. For instance, the radical addition of hypohalites is a suitable high-yielding approach toward polyfluorinated aliphatic ethers and esters

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• of the Co–H to the alkene but of a step-wise radical addition. A similar procedure was reported by Herzon [85]. His study focused on the use of two reductants, triethylsilane and 1,4-dihydrobenzene (DHB) (Scheme 24). He showed that in the presence of DHB, the intermediate radical could be trapped by

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

• , reaction 2). Two classes of reagents are commonly used: ethynylbenziodoxolones (EBXs) [32][33] and alkynylsulfones [34]. A potential limitation of this method lies in the substitution of the transferred alkyne. The efficiency of the radical addition to those reagents is known to be highly dependent on the

• remaining (Table 1, entry 15). Styrene was initially selected as model substrate since the addition of azide radicals generated by ABX was well reported [24][29]. We wanted to explore different classes of alkenes as the double bond substitution would greatly impact both the azide radical addition and the

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

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

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

• undergo addition to the heterocyclic radical acceptor 19 through a ternary transition state 20 involving hydrogen bonding interactions with the chiral phosphate co-catalyst. Notably, a follow-up report revealed that the radical addition is reversible, and that the selectivity determining step involves the

• the phthalimide moiety (Scheme 7B). Thus, the excited state reductant *IrIII reduces the activated substrate 29 to form the stabilized radical anion 30. Fragmentation into radical 9, followed by radical addition to styrene gives benzyl radical intermediate 26. Turn-over of the catalytic cycle through

• Stern–Volmer constant (Ksv = 1146 M−1 with acid vs Ksv = 603 M−1 without acid). The reaction mechanism continues with the fragmentation of 33 into radical 34. From radical 34 the annulation reaction initiates via intermolecular radical addition, resulting in the formation of intermediate 35. After

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

•  15) [27]. This method involved a series of steps, including the formation of an EDA complex, decarboxylation, radical addition, C–H functionalization, and annulation. Various primary, secondary, and tertiary alkyl N-hydroxyphthalimide esters 33 showed potential as viable substrates for the synthesis

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• be more widely employed. 2 Other polymerization techniques involving radical chemistry As discussed in section 1, chain-growth polymerization via radical addition to vinyl monomers is the most broadly applied polymerization technique. However, radical chemistry is used in other polymerization systems

• ]. In a typical thiol–ene system, the polymerization undergoes a free-radical chain mechanism, involving an initiation step from a thiol group via radical transfer or homolysis (Scheme 11, initiation), radical addition of the thiyl radical to the ene functionality (propagation 1), transfer from the

• Radical addition is a popular technique for post-polymerization modification of double-bond-containing polymers (Scheme 14). Thiol–ene and thiol–yne “click chemistry” are highly efficient radical processes well-adopted in synthetic chemistry, material fabrication, and chemical biology (cf. section 2.2

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• a radical addition mechanism. This is further supported by the result of an I-atom transfer experiment (Scheme 7, top). In the presence of two equivalents of iPrI, the reaction of 8a with Et2Zn leads to a mixture of product 14a and product 25a, incorporating an iPr moiety, in a 14a/25a 30:70 mixture

• . Product 25a is formed on addition of an iPr radical generated by I-atom transfer from iPrI to the Et radical, and is diagnostic for the formation of the latter in the reaction medium. Deuterium labeling experiments were then performed to substantiate the formation of a zinc enolate following radical

• addition (Scheme 7, bottom). Much to our surprise however, no deuterium incorporation is observed on quenching with ND4Cl/D2O the reaction between 8a and Et2Zn. By contrast, a significant deuterium incorporation is obtained when deuterated starting material (8a-d) is engaged. The combination of these two

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• driven by several key features of RLT catalysis, including the ability to form diverse bonds (including C–X, C–N, and C–S), the use of simple earth abundant element catalysts, and the intrinsic compatibility of this approach with varied radical generation methods, including HAT, radical addition, and

• of RLT with photoredox-catalyzed atom transfer radical addition (ATRA) (Scheme 3). ATRA results in the net addition of a C–X bond across an alkene, forming both valuable C–C and C–X bonds in a single reaction. While ATRA-type reactions were first reported in the 1940s by Kharasch [28], interest in

• species. Areas of recent work on RLT development and application in catalysis. I: Reported RLT pathways often involve the generation of alkyl radicals from selective HAT on C–H bonds and, more recently, radial decarboxylation and radical addition onto π systems. Generated alkyl radicals are simultaneously

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• ]. In 2019, the Prato group demonstrated how the PDI catalyst first disclosed by the König group (vide supra) could be leveraged for conPET reductions of perfluoroalkyl iodides, providing a photocatalytic alternative for the generation of perfluoroalkyl radicals used in atom transfer radical addition

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• )PF6 (E1/2*III/II = +1.21 V, E1/2III/II = −1.37; E1/2IV/*III = −0.89, E1/2 IV/III = +1.69 V) [74] would permit efficient radical generation and C(sp3)–C(sp3) bond formation either by challenging selective radical–radical cross-coupling or by radical addition to a π-bond, enabling a rare example of

• diene [90][91]. In addition, these results support the hypothesis that the decarboxylative cyclization can occur through subsequent selective 6-exo-trig radical addition. It also has been reported that it is difficult to detect which intermediate is really involved, since they are easily

• radical addition–fragmentation on the latter and most likely to shift the regioselectivity towards 6-exo-trig by a favorable interplay of polar effects [99] failed and furnished only the 1,3-diene 10. Unfortunately, when substrate 10 was subjected to the reaction conditions shown above, only tarry

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• in the formation of spirolactam 157 in 73% yield (Scheme 13). The reaction is estimated to take place initially with the one electron reduction to α-amino radical 164. This step is thought to be facilitated after TFA protonates the formed imine. Afterwards, radical addition of 164 to 156, generates

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• -coupling involving aldehyde C–H bond cleavage. DABCO-derived cationic catalysts in inactivated C–H bond cleavage for alkyl radical addition to electron-deficient alkenes under photoredox catalysis conditions. Electrochemical diamination and dioxygenation of vinylarenes catalyzed by triarylamines