Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• different transition-metal complexes have been employed in metalloradical catalysis, including porphyrin complexes of cobalt(II) [55][56] and iron(III) [57][58]. Both cobalt in oxidation state +2 and iron in oxidation state +3 can be viewed as persistent metalloradicals. Zhang and co-workers reported a

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• activation; C–H annulation; iron metal catalysis; quinolines; styrene; Introduction Quinolines are one of the essential heteroaromatic motifs that play a crucial role across diverse scientific fields due to their wide range of applications. In contemporary medicine, quinoline derivatives frequently appear

• herein report the first example of the earth-abundant iron-catalyzed oxidative cleavage of C(sp2)–C(sp2) bonds of styrenes and further utilization of the intermediates as dual synthons for the synthesis of two essential quinoline moieties as shown in Scheme 1b. Results and Discussion To validate our

• cleavage of styrenes, catalyzed by earth-abundant iron, followed by the in-situ utilization of the resulting cleaved synthon in a domino process to synthesize highly substituted quinoline derivatives. We have demonstrated that this process can efficiently convert readily available feedstocks, including a

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• . GluAC4A effectively promotes drug accumulation in the brain. Moreover, the Lip@GluAC4A complex significantly reduces iron deposition, blood-brain barrier leakage, and neurological deficits that are commonly observed with rtPA treatment. 2.5 Multi-responsive controlled release The previous sections

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• ]. Unfortunately, testing of malassezione is limited by the lack of a convenient synthesis. Indeed, beyond isolating the compound from cultured M. furfur [11][20], the only reported synthetic route to malassezione is via an iron-catalyzed Fukuyama-type indole synthesis, which afforded the compound in low yield [18

• subsequent iron-catalyzed reaction afforded 1 in only 35% yield. To avoid the low-yielding preparation of the isonitrile, we elected to use commercially available indole-3-acetic acid as the starting material, and to utilize an approach similar to that described for the synthesis of dibenzylketones from the

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• released by microorganisms into their surrounding extracellular environment to chelate iron and selectively import it into the microbial cells [12][13]. It has been suggested that the release of siderophores by soil-dwelling pseudomonads give them an ecological edge by creating an iron-deprived environment

• previously described. Even, salicylic acid, a precursor in the biosynthesis of salicylate-derived siderophores confirmed the metallophore tendencies of the isolated compounds produced in iron-deficient environments [29][30][31]. Biological evaluation Compounds 1–7 were evaluated for their antiparasitic

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

• value in organic synthesis. Introducing a bromine or chlorine atom into aliphatic C–H bonds with high site selectivity and efficiency poses a formidable challenge. Traditional strategies for the halogenation of aliphatic C–H bonds typically rely on biomimetic iron-catalyzed oxidation systems that

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

• , heteroarylmethanes, phenylethane, and cumene proved compatible with the reaction conditions, providing oxindoles 3a–k with yields ranging from 67% to 86%. As illustrated in Scheme 2, an iron-catalyzed difunctionalization of alkenes involved in intramolecular transformations involving a C(sp3)–H bond adjacent to a

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

• (CO)12, to catalyze the alkyne hydrocarbonylation using CO and ZrF4 as the co-catalyst. The reaction afforded the corresponding amides 133, 277, and 278 in good yields via acyl carbonyl iron intermediate 280, which was observed by NMR (Scheme 69) [118]. By applying less toxic and safer CO2 instead of

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• h (Scheme 13). It should be noted that the reaction failed to give good results using Ni or Fe as the anode (<10%). However, using an iron/nickel alloy electrode with 64% iron and 36% nickel gave good results. This method can also be applied to heteroaromatic bromides, although it shows an increased

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

•  1, entry 3). When iron(II) sulfate (FeSO4) and iron trifluoromethanesulfonate (Fe(OTf)2) were used as the catalyst instead of copper(II) trifluoroacetate (Cu(TFA)2), the yields of the product were decreased (Table 1, entries 4 and 5). Using palladium(II) acetate (Pd(OAc)2) as the catalyst provided a

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• , methyl aryl ketones, and DMSO under iron(III) catalysis and using K2S2O8 for its activation [39]. The proposed mechanism is very close to those described above, with the methyl aryl ketone taking part of the reaction in place of the styrene component in the Povarov cyclization. In this case, the imine

• , 5 mol %) [63], indium (as In2O3 nanoparticles, 5 mol %) [64], iron (as FeCl3, 20 mol %) [65], cobalt (as CoBr2, 10 mol %) [66], and nickel (as Ni(py)4Cl2, 15 mol %) [67] can act as metal catalyst for the 3CC reaction. In all these cases, the temperature was lower (usually between 60–80 °C) compared

• to the AAA coupling, except for iron, where the temperature must be increased to 100 °C. This can be explained in terms of the activation of both the C–H and C–X bonds by metal catalysis, which is not the case in AAA couplings, where only the C–H bond is activated, making the last step (nucleophilic

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

• -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

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

• band. These combined effects can be illustrated in the case of the [M(phen)3]2+ set with iron, ruthenium, and osmium (Figure 1). For a same phenanthroline ligand, these three complexes show an MLCT absorption band at different wavelengths, i.e., 522 nm for [Fe(phen)3]2+ [14], 449 nm for [Ru(phen)3]2

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• disulfides, it is typically necessary to introduce equivalent reducing agents, such as PPh3 [29], HI [30], HPO(OEt)2 [31] or iron powder [32] into the reaction mixture. Although there have been numerous studies on the synthesis of disulfides from sodium sulfinate, the development of a method to synthesize

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

• solutions [18]. Similarly, Burns and co-workers reported di- and tetra-urea picket porphyrins highlighting, the impact of buried solvent molecules, such as DMSO, on the selectivity, affinity, and stoichiometry of anion binding [19]. Iron complexes of tetra-urea picket porphyrins further demonstrate how

• functional versatility [44], and many of these resulting metal complexes are catalytically active [45][46][47]. These synthetic metalloporphyrins take inspiration from biological systems, such as hemes (iron complexes), chlorophylls (magnesium complexes), and vitamin B12 (cobalt complex). Contrary to

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• , they serve as ligands for chelating iron in siderophores. Because ferric cations (Fe3+) mostly exist as insoluble solids in the Earth crust, most microorganisms produce and secrete siderophores to scavenge this scarce resource from their surroundings [67]. Whereas siderophores do not always contain

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

• ) [51]. The corresponding peroxides 30 are enough stable under the reaction conditions and were isolated in high yields (Scheme 12). Flow-modification of the 2-oxoindole peroxidation method using nanoparticles of iron oxide as the catalyst was proposed [52]. The summarized proposed reaction pathway is

• oxidation of cyclohexane 83 with TBHP using mononuclear [77][78][79] and dinuclear [80] non-porphyrin iron complexes (Scheme 30). Besides the oxygen atom transfer products, cyclohexanol (85) and cyclohexanone (15), the formation of peroxide 84 was observed. Oxidation of cyclohexane (83) was also carried out

• leads to the formation of the target product 139. Later, iron-catalyzed three-component reactions of α,β-unsaturated carbonyl compounds 140, aldehydes 141, and TBHP leading to α-ester-β-keto peroxides 142 have been developed (Scheme 45b) [106][107][108]. Radical coupling of arylaldehydes 144 with α,β

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• method of controlling fungal infections. The mechanism of inhibition of azoles and their derivatives is based on the formation of a coordination bond between their heterocyclic nitrogen atom, which carries an unshared electron pair, and the haem iron atom. The formation of this bond leads to inhibition

• compounds 4a–e and 5a–e to CYP51 and to evaluate which of these molecules could act as inhibitors of the enzyme. As mentioned above, CYP51 inhibitors contain a heterocyclic nitrogen atom that forms a coordination bond with haem iron. Therefore, only those compounds that could form such a bond according to

• fingerprints (IFP) between the docking ligands and the protein shows that, similar to the reference ligand voriconazole, the compounds interact with the protein through hydrophobic interactions with hydrophobic residues of the protein and the formation of coordination bonds with the haem iron (Table 3). At the

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• described as planar 18π aromatic macrocycles; however, molecular structure analysis frequently reveals nonplanar ring distortion [2][3]. In fact, porphyrins with nonplanar ring distortions are vital for many natural processes to occur, e.g., nonplanarity can alter oxygen affinity of the metal iron core [4

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

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• conducted without solvent. In a similar approach, Khan et al. succeeded in synthesizing pyrazole-4-carbodithioates 67. The products are prepared from phenylhydrazine, aldehydes, and alkyl-3-oxo-3-arylpropane dithioates 66 catalyzed by iron sulfate (Scheme 22) [100]. In this method, aliphatic aldehydes as

• )-cycloaddition of nitrile oxides 137, generated in situ from hydroxyiminoyl chloride 135 and terminal alkynes, was proposed by Kovacs and Novak. Copper supported on iron serves as a catalyst and as a reagent for the reductive ring opening and leads to β-aminoenones 139, which react in the consecutive one-pot

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• ][28]. However, the selectivity of these photoredox reactions is driven by the structural properties of the heteroaromatic ring. During the preparation of this article, the Meggers group published an outstanding enantioselective iron-catalyzed α-amination pathway (Scheme 1b) [29]. The method is widely

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• , introduce hydroxy groups at C8 and C16 to produce FD-8β,16-diol (7), and BscE-catalyzed O-methylation generates the putative intermediate 8. The subsequent oxidative allylic rearrangement (8→9), catalyzed by the nonheme iron(II) and 2-oxoglutarate (Fe(II)/2OG)-dependent dioxygenase BscD, was a key step

• toward developing a chemo-enzymatic synthetic process. Presumably, the reactive iron(IV)-oxo species in dioxygenase BscD abstracts an allylic hydrogen at C1 and generates intermediate A. Subsequent α-face-selective hydroxylation of the resulting allylic radical at the C3 position would yield brassicicene

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• directing group strategies, this approach opens the door to fluorinating a wider range of benzylic substrates. Metal catalysed In 2013, Lectka and co-workers reported an iron(II)-catalysed benzylic fluorination with Selectfluor (Figure 11) [49]. The authors were able to use an inexpensive iron source to

• intramolecular fluorine-atom-transfer (FAT) from an N-fluorinated amide to a pendant carbon-based radical formed from an iron catalyst (Figure 15) [55][56]. This concept of fluorine transfer through a 6-membered transition state was shown to work efficiently from primary, as well as secondary, benzylic radicals

• the loadings of K2S2O8 and Selectfluor, selectivity for the mono- (conditions A) or difluorination (conditions B) products could be achieved. Building on their previous iron-catalysed work, Figure 11, Lectka and co-workers reported in 2014 the use of triethylborane as a radical chain initiator for C