Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

•  23) based on the rebound triplet mechanism [64]. The stereochemical behaviour of the reaction is controlled by a novel hydrogen-bonding chiral iridium photocatalyst 86, delivering oxetane products 87 in excellent enantiomeric excess. In this unique photocycloaddition mechanism, previously described

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• the photocatalyst [Ir(dF(CF3)ppy)2(4,4'-d(CF3)bpy)]PF6 in combination with a base (NBu4OP(O)(OBu)2) (Scheme 1) [59]. The generation of amidyl radical 5 involved a stepwise PCET process catalyzed by the combined effect, in the presence of photocatalyst and the base. Subsequently, amidyl radical 5

• radical anion 15 was reduced by the photocatalyst Ir(Fppy)3 from the reagent 11. The resulting anion 14 underwent aromatization to release a nitrile anion, subsequently yielding product 12. This strategy also successfully produced products 16 and 17 with yields of 85% and 56%, respectively, from

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• . Notably, an equivalent amount of TBHP was required as an oxidant to regenerate the photocatalyst. Various substituents, including electron-donating and electron-withdrawing groups on the aryl ring of N-arylacrylamides, such as p-Me, p-MeO, p-MeO2C, p-CF₃, p-Cl, and p-pinB, were compatible with this

• -transfer (SET) process occurred efficiently under blue LED irradiation in the presence of Ir[dF(CF3)ppy]2(dtbbpy)PF6 as the photocatalyst. This was followed by deprotonation and radical migration, yielding α-aminoalkyl radical A, which added to the intramolecular C=C bond of N,N-dimethylaniline to produce

• alkyl radical intermediate 1. Subsequently, radical cyclization and deprotonation, assisted by the tert-butoxy radical, led to the desired products 26. It is important to emphasize that TBHP plays a crucial role as an oxidant in regenerating the photocatalyst for the catalytic cycle. In the same year

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• -workers (2022) functionalized Weinreb amides through organophotocatalytic N–O cleavage via 114 and 115 to give the corresponding primary amides 111–113 in good yields (Scheme 34) [27]. Xie and co-workers (2022) synthesized cinnamamide 83 mediated by [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (PC-1) as photocatalyst

• , metathesis reactions have also been applied to stereoselectively synthesize cinnamic acid derivatives. For example, Lakhdar and co-workers (2022) combined E-selective Grubbs second-generation catalysts (cat 7) with photocatalyst (PC-4) to convert styrenes and methyl acrylate (444) into the corresponding (Z

• )-cinnamic acid esters 445–448 in excellent yields via E-to-Z photoisomerization mediated by the photocatalyst (Scheme 90) [152]. Nguyen and co-workers (2019) employed iodine to catalyze the intermolecular olefin-carbonyl metathesis reaction of benzaldehyde (449) and acrylate 450 to give the corresponding

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• demonstrate that these simple D–A structures exhibit promising photocatalytic properties, comparable to those of more complex D–A–D systems. Keywords: donor–acceptor system; photocatalyst design; photoredox catalysis; organic photocatalyst; Introduction In recent years, photocatalysis has emerged as a

• power (E*red up to 1.5 V) can be classified as a bimodal photocatalyst. This type of molecule is capable of driving both oxidative and reductive reactions, thereby offering significant versatility to achieve photocatalytic transformations. To our delight, molecule 5a possesses a promising E*ox =−1.89 V

• facilitated by reduced photocatalyst (PC) and the interaction of 15 with the radical cation of DIPEA. The best result, again, was attributed to molecule 5a with 60% isolated yield (Table 5, entry 1). In contrast, molecule 5b showed the worst performance with 41% NMR yield (Table 5, entry 2). For compounds 5c

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• prohibitively high in energy for selective reactivity [5]. The inception of energy transfer catalysis (EnT) has expedited discoveries concerning the photoactivation of organic molecules [15][16][17], enabling direct access to the triplet excited state through the use of a photocatalyst (Figure 1A, top

• the alkene leading to the generation of an 89:11 (E/Z) mixture of geometrical isomers (Table 1, entry 3). The use of xanthone (74 kcal/mol), a highly powerful organic photocatalyst, enabled enhanced reactivity producing a photostationary state of 73:27 after 16 hours (Table 1, entry 4). Varying

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• oxygen [42]. Through energy transfer (EnT) from the ruthenium-based photocatalyst to triplet oxygen, singlet oxygen is produced in a targeted manner, which oxidizes histidine to an endoperoxide, significantly increasing its reactivity toward nucleophiles (Figure 4A). This strategy employs a

• of the ArM significantly enhances the potential of the photocatalyst for antibody modification [43]. By inserting a [Ru(bpy)2dppz]2+ complex into the apo-form of riboflavin-binding protein (RFBP), a complete reversal of selectivity was achieved: the Ru complex alone enabled tyrosine modification via

• method allows the same photocatalyst and electrophile to be involved in two different but selective bioconjugations of mAbs. It remains limited to reactions involving oxidative mechanistic pathways with 1O2. Cys In 2016, Bräse et al. developed a photomediated disulfide rebridging method, exploiting the

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

• rearrangements. Most organic molecules are colorless and, in fact, do not absorb visible light: highly energetic UV irradiation is typically needed. A milder approach is offered by photocatalytic approaches. Here, a photocatalyst is added to the reaction mixture to convert light energy into chemical potential to

• transform molecules. Intriguingly, photocatalysts typically absorb harmless visible light and can be chosen ad hoc to trigger the desired chemistry. Indeed, the photocatalyst–substrate interaction can occur via energy transfer [4][5][6][7][8], single-electron transfer [9][10][11][12], or hydrogen-atom

• -workers in 2022. They reported the photo-thermo-mechanochemical approach for the synthesis of quinolines from sulfoxonium ylides and 2-vinylanilines promoted by an iron(II) phthalocyanine (FeIIPc) photocatalyst (Scheme 3) [65]. First, a mixture of 2-(1-phenylvinyl)aniline (3.1), sulfoxonium ylide 3.2, and

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• -selective reactions [21][185][430][431][432][433]. Cage structure may also activate photocatalysts [434] or help restrict detrimental photocatalyst deactivation reactions [435]. We also point towards conformational autodesymmetrization [39] as a largely ignored strategy to develop low-symmetry cavities

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

• catalysis in recent years not only with heavy metals such as ruthenium and iridium [1][2][3][4][5], but also with lighter elements [6][7][8]. This field of light-mediated organic transformations relies on the use of a photocatalyst to promote radical reactions through electron transfer between this former

• excitation to the triplet state from the ground state S0. This effect mitigates rapid back-electron transfer from the singlet excited state to the ground state, extending the excited-state lifetime of the photocatalyst. Since the T1 → S0 transition is spin-forbidden, the process increases the overall

• study found that by using [Os(phen)3]2+ as the photocatalyst and 660 nm red light, the reaction exhibited greater functional group tolerance, handling a variety of electron-deficient, neutral and rich (hetero)aryl bromides 9 and primary and secondary amine-based nucleophiles 10 with minimal degradation

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• CF2HCO2H or PhCF2COOH, along with benzimidazoles bearing unactivated alkenes and PhI(OAc)2 as substrates, and proceeded without the need of any base, metal catalyst, photocatalyst or additive. In total, 24 examples were examined, and all of them successfully underwent cyclization reaction to produce the

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

• products and drugs has proven to be useful in these reactions. As shown in Figure 7, the photocatalyst sodium anthraquinone-2,7-disulfonate (AQDS) is excited by 395 nm light to form AQDS* and undergoes electron transfer with arylalkanes 20 to generate an ion-radical pair (AQDS•−, 20•+). This ion radical

• products with high enantioselectivity. The catalytic cycle is depicted in Figure 7. The photoexcited photocatalyst anthraquinone (AQ*) acts as a hydrogen-atom transfer (HAT) acceptor and transforms the alkylarene 20 into benzylic radical intermediate 23 together with reduced [AQ–H]•. The benzylic radical

• enantioenriched nitrile products 29. The proposed mechanism is illustrated in Figure 8. [Mes-Acr-Ph]+* is generated through the photoexcitation of the photocatalyst [Mes-Acr-Ph]+, which undergoes electron transfer to the heteroarene 28, resulting in the formation of the [Mes-Acr-Ph]• and heteroarene radical

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• and sulfur dioxide afforded vinyl sulfones with excellent regio- and stereoselectivity (Scheme 9) [22]. The authors used DABCO(SO2)2 to generate sulfur dioxide, and visible light irradiation and the mandatory presence of a photocatalyst for this transformation suggested a radical mechanism. The

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

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

• photocatalyst (Figure 1d) [25]. Noël et al. [26] have further extended this approach to include alkyl bromides (Figure 1e) [26]. Despite the effectiveness of the photolysis, benzophenone derivatives have also been shown to enhance the productivity of silane-mediated conjugate additions, using alkyl halides [27

• initial reaction, using CH3CN as solvent, led to formation of methyl 3-cyclohexyl-2-(1,3-dioxoisoindolin-2-yl)propanoate (3, 51% yield, 85% conv.; Table 1, entry 1). To demonstrate the importance of the photocatalyst, BP l was excluded (Table 1, entry 2), resulting in a slightly higher conversion and a

• 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

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• -workers reported using metal-free planar H2TPP (18) as a photocatalyst for the photoredox-α-alkylation of aldehydes with ethyl diazoacetate [91]. This reaction achieved an impressive product yield up to 84%. Control experiments showed that omitting any one of the reaction components – such as the

• various amines tested, only the secondary amines (morpholine) led to product formation, confirming the formation of enamine in the catalytic cycle. The proposed mechanism suggested that the amine, photocatalyst, and light each played crucial roles (Figure 14). The porphyrin acted as both a photoredox unit

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

• -AcrClO4 as the photocatalyst has been disclosed (Scheme 24) [67]. According to the authors, the irradiation of the photocatalyst (Acr+-Mes) A with a blue LED leads to the excited state (Acr·-Mes·+) B. The aliphatic carboxylic acid 66 is converted by deprotonation to the corresponding carboxylate, which is

• oxidized by the excited photocatalyst to give the benzyl radical D and CO2. Further, single electron transfer from (Acr·-Mes) C to TBHP results in the ground state photocatalyst (Acr+-Mes) A and tert-butoxy radical E, which abstracts the hydrogen atom from TBHP to yield tert-butylperoxy radical F. The

• recombination of radicals F and D leads to the product 67. Photochemical peroxidation of isochromans and other benzylic C(sp3)–H substrates 68 with TBHP was developed using Ir(ppy)3 as the photocatalyst and Bronsted acid as an additive (Scheme 25) [68]. Visible light irradiation of [IrIII(ppy)3] to give the

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• position of quinoline N-oxides and pyridine N-oxides, utilizing hypervalent iodine salts as the arylation reagents. The reaction was facilitated by visible light in conjunction with a photocatalyst. The absence of either the photocatalyst or light resulted in only trace amounts of the product, underscoring

• their essential roles in product formation. Optimized conditions comprised the reaction of the quinoline N-oxides 25 (1 equiv) with diaryliodonium tetrafluoroborates 26 (2 equiv) as the arylating agent, 1,4-benzoquinone (BQ) as an additive (2 equiv), the photocatalyst eosin Y (10 mol %), and Cs2CO3 (1

• intermediate I. Furthermore, intermediate I subsequently undergoes another SET reaction, resulting in intermediate II and the regeneration of the photocatalyst. Intermediate II undergoes deprotonation, facilitated by the presence of Cs2CO3 as base, to yield the final products 27 or 29. Additives like BQ likely

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

• into a carbon radical intermediate. The photocatalyst then oxidizes this intermediate, leading to the final product (Scheme 45). This approach underscores the significant potential of combining electro- and photocatalysis to achieve selective and mild transformations in organic synthesis, particularly

• disclosed a similar trifluoromethylation of arenes under photoelectrochemical reaction conditions but without the addition of a photocatalyst, using trifluoroacetic acid as the CF3 source (Scheme 47b) [71]. This alternative approach further underscores the versatility and applicability of

• bonds is challenging due to the risk of overoxidation. Recently, Lambert and coworkers explored the photoelectrochemical multiple oxygenation of C–H bonds using trisaminocyclopropenium (TAC+) as a photocatalyst [74]. This method enables the transformation of alkylarenes into the corresponding di- or

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• ; photocatalyst; sunlight; Introduction The furan ring moiety is present in several natural products [1] and serves as a key precursor to 1,4-dicarbonyls [2], cyclopentanones [3], and carboxylic acids [4], in synthetic organic chemistry. Furfuryl alcohols, a family of 2-substituted furan molecules, are

• more efficient processes and potentially higher yields compared to the batch processes [23]. The first photoredox-mediated Achmatowicz reaction was reported by Gilmore et al. [13] in batch mode utilizing furfuryl alcohols with Ru(bpy)3Cl2·6H2O as photocatalyst, Na2S2O8 as an oxidant and H2O/DMSO/MeCN

• light and biomass-derived furfuryl alcohols as starting material making it more environmental benign. Results and Discussion A batch process Achmatowicz rearrangement mediated by less expensive rose bengal as photocatalyst (PC) was first reported by Vassilikogiannakis et al. [24] and was further

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

• reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in

• the linked alkene moiety, followed by hydrogen transfer from the hydrogen atom transfer (HAT) catalyst. This process was used to successfully prepare 2-alkylated clavam derivatives. Keywords: β-lactam; acridinium photocatalyst; alkenes; amides; intramolecular radical reaction; photoredox catalysis

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• reactions in a less protic and less polar solvent. Attaching catalysts to solid supports also offers the potential for enhancing catalyst stability. Boyer and co-workers reported the use of silica nanoparticle-supported eosin Y 21 as a photocatalyst in reversible addition fragmentation chain transfer (RAFT

• ) photo-polymerisation reactions (Scheme 6) [24]. Previous endeavours utilising the homogeneous catalyst led to catalyst degradation or failure to remove the catalyst properly which resulted in the degradation of the polymer itself [66]. By employing the supported photocatalyst, reduced contamination was

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

• metal complex or functional dye as a photocatalyst (PC) [19][20]. Recently, some important reviews summarize and discuss the use of method 3 in synthetic organic chemistry [21][22]; in contrast, there is little detailed and coherent literature on the overall research trends regarding the latest research

• methods, methods 1 and 3 require the addition of a radical initiator and a photocatalyst, respectively. In contrast, method 2 does not require any additive, although, if the heating or photoirradiation is performed by electricity, the combustion of fossil fuels may cause environmental pollution. However

• • can be generated by photoirradiation. On the other hand, the photoinduced homolysis of groups 13 and 14 interelement compounds with B–B, Si–Si, Sn–Sn bonds, etc. is generally impossible, because such E–E compounds have no isolated electronic pair. Therefore, the use of a photocatalyst (method 3) or

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• photocatalyst TAC+. The electrolysis was carried out at a constant cell potential of 1.5 V under white light irradiation. The carbonyl compound 144 was initially treated with tert-butyl carbazate (145) in acetonitrile in the presence of molecular sieves, followed by the addition of trifluoroacetic acid (TFA) to

• yield the unsubstituted hydrazone 146. Dropwise addition of this solution during the electrolysis to the anodic chamber containing the olefin 147, lithium perchlorate and the photocatalyst in acetonitrile delivered the desired olefin product 148. From a mechanistic point of view, the

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

• 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