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

• (CuCl2, NaNO2, TEMPO) using molecular oxygen as a terminal oxidant have also been used [12]. Nevertheless, neither of these conditions was successful when they were applied to methanol to generate formaldehyde, because overoxidation is an important side reaction in these cases [12][13][14][15]. However

• ). Additionally, the Tiwari group developed a metal-free protocol using only K2S2O8 as an oxidant for the activation of DMSO to MMS (Scheme 8, path II) [38]. Under these conditions, an alternative mechanism arises in which the imine intermediate B, formed as previously stated through reaction between the aniline

• to the resulting compounds. Once again, DMSO was confirmed as the origin of the methylene bridge by isotope labelling experiments using DMSO-d6. The proposed mechanism comprises the activation of DMSO by a Ru(III) catalyst and the role of Selectfluor working as the oxidant that allows the "activation

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

• investigated. When o-terphenyl (10.1) was milled (30 Hz, PTFE balls) and irradiated (λ = 270 nm) in the presence of silica gel (bulking agent), I2 (1 equiv) as an oxidant, and K2CO3 (1 equiv) as a base in the presence of toluene, the expected product 10.2 was obtained in 81% yield after isolation upon 181 h of

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

• detail, and the authors have proposed that the reaction proceeds through a photoinduced electron transfer mechanism (Scheme 11). Upon red-light excitation, chlorophyll generates superoxide anion radicals (O2•−) in the presence of oxygen, which act as the active oxidant to convert organoborons 31 to

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

• Cu-catalyzed electrochemical C–H activation strategy through C–H alkynylation of arylamides followed by electrooxidative cascade annulation (Figure 4) [48]. This reaction enables sustainable C–H functionalization by utilizing electricity as the terminal oxidant instead of stoichiometric amounts of

• employing electricity as an oxidant (Figure 11) [60]. Mechanistic studies have indicated that n-Bu4NI acts as a redox mediator at the anode, and the electron transfer between the copper complex and the iodine radical is the rate-determining step. The author proposed a catalytic cycle, as illustrated in

• , the Xu group developed a Cu-catalyzed electrochemical azidocyanation of alkenes (Figure 17) [72]. This alkene difunctionalization, using TMSCN (21) and TMSN3 (98) as starting materials, features oxidant-free conditions, compatibility with both aryl- and alkylalkenes, and a wide functional group

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

• process by using α-diazoketones, nitroalkenes and primary amines, in the presence of air as oxidant. The mechanism involved the formation of α-ketocarbene XXVI from α-diazoketone, able to react with the amine affording imine XXV after copper-catalyzed oxidative dehydrogenation. The subsequent [3 + 2

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

• reaction conditions, two different products were formed. Arylbenzoindoles 212 by standard conditions with 5 mol % catalyst loading and naphthylindoles 213 by utilization of an oxidant with only 1 mol % catalyst loading. Under these optimized conditions, decent yields and remarkable enantioselectivities

• . Transition-state calculations gave insight into possible reaction pathways. CPA C48-activated substrates react and rearomatization of the benzene ring leads to the intermediate Int-66. In the presence of an oxidant, axially chiral product 213 is formed. Otherwise, nitrogen-initiated intramolecular

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• as an oxidant [63]. A gas−liquid segmented or a tube-in-tube strategy was adopted to achieve a higher yield within a shorter residence time. Substantial further developments have been made in applying ASFR in multiobjective optimizations, which will be discussed in detail below in the section

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• carbocycles can be synthesized mildly and effectively using HVI reagents. Nitrogen nucleophiles A metal-free synthesis of β-fluorinated piperidines was reported in 2012 by Meng, Li and co-workers (Scheme 1) [26]. The authors describe a reaction using PhI(OPiv)2 as oxidant with HF·pyridine as the source of

• products or stabilised by the tosyl group and subsequently attacked to form only the cis product in an SN2 reaction. Liu and co-workers reported a palladium-catalysed intramolecular aminofluorination of unactivated alkenes [27] (Scheme 2) in the presence of PhI(OPiv)2, AgF and MgSO4 as an oxidant, source

• the product. Li reported a haloamination of unsaturated amines in 2014 (Scheme 5) [30], to form fluorinated piperidines 6 using PhI(OAc)2 as an oxidant and BF3·OEt2 as the source of fluoride. Fluorocyclisations gave lower yields compared to other halocyclisations reported by the authors

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

• -t-Bu)2. Allylic peroxidation of 3-substituted prop-1-ene-1,3-diyldibenzenes 8 was performed with TBHP as the oxidant/peroxidation agent and with Cu2O as the catalyst [42] (Scheme 6). The proposed mechanism of peroxides 9 formation does not include peroxo–copper complexes and begins with the

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• of 5-thioxo-1,2,4-triazolium inner salts by the nucleophilic thiocyanation of N,N-dialkylhydrazonoyl bromides, in situ generated from aldehyde-derived hydrazones in the presence of an oxidant (NBS, (NH4)2S2O8), Scheme 1). In 2024, the synthesis of 2‑imino-1,3,4-thiadiazoles was achieved by

• expected product was detected (Scheme 4C). Having in mind that in the presence of an oxidant, the SCF3 dimer (SCF3)2 might be generated, an additional test was realized. In the presence of NCS in THF, AgSCF3 was converted into the corresponding dimer in 5 min (monitored by 19F NMR). Then, the reaction was

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• an external oxidant in combination with a multicomponent process allows to improve the scope of known MCRs by broadening the diversity and availability of starting materials, or by transforming unstable multicomponent adducts into stable compounds. Following our research interest in developing new

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• in two different ways: with metallophthalocyanine catalysts present and by including hydrogen peroxide as a co-oxidant (Scheme 1). Metal–phthalocyanine complexes (PcM) are recognized as catalysts for gentle, particular oxidation reactions under aerobic [14] and H2O2-based conditions [15][16][17][18

• − ion, which is formed by the non-radical decomposition of the peroxydisulfate ion in a strongly alkaline medium [34]: The Elbs and Boyland–Sims reactions were also effectively modified by the use of H2O2 as a co-oxidant (binary oxidation mixture APS/H2O2). Adding 2.0–2.3 equiv of H2O2 (Table 3) [35

• oxidized more completely due to a more efficient consumption of the oxidant (APS). Previously, the oxidation of orotic acid was studied and it was found that the presence of oxygen in the reaction medium affects the yield of the sulfate derivative [37]. Under anaerobic conditions, a low yield of the

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

• manner. Towards this direction, few research groups have already reported the Achmatowicz reaction utilizing greener approaches, yet they suffered due to some limitations. Sun et al. [20] have successfully demonstrated an Achmatowicz rearrangement using electricity as a green oxidant (Scheme 1c) in a

• 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

• details in Supporting Information File 1, Table S1, entries 10–18), it was discovered that a combination of ACN/DMSO/H2O solvent, K2S2O8 oxidant, Ru(bpy)3Cl2·6H2O photocatalyst, and 28–34 °C temperature were the best-suited and optimized reaction conditions. After optimization, our efforts were put

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

• , enhances charge transfer by stabilizing the mesityl moiety. Conversely, the introduction of tert-butyl groups increases the life time of the excited state [52][53][54][55][56]. As a consequence, the PC IV is a strong oxidant in the excited state and displays unique oxidizing properties (E1/2[*PC+/PC

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• usefulness for the epoxidation of the β-CF3-α,β-unsaturated ketones [40], we applied this method at first for the epoxidation of 1b. However, contrary to our anticipation, only a total recovery of the substrate was observed, and further search for an oxidant reached the usage of a NaClO aqueous solution with

• detection of benzaldehyde which was considered to be formed by the NaClO-mediated oxidation of benzyl alcohol generated by hydrolysis. Changing the oxidizing reagent to crystalline NaClO·5H2O nicely solved the problem with the realization of 86% isolated yield of 2b by the utilization of this oxidant (2

• higher temperature especially in the case of compounds 1e and 1f as well as the high loading of the oxidant in the latter might be due to their higher oleophobicity by possessing longer Rf chains. For all instances, epoxyesters 2 were obtained as single E-isomers, and based on the result obtained by the

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• action of a soft oxidant a bis-(neo-cuproine) copper(II) complex. The CUPRACTEAC parameter varies in a wide range of values from 0.12 to 1.92 (Table 2). Compounds 1 and 2 containing a 1,3,4-oxadiazole ring and a sulfur atom directly bonded to the catechol ring are practically inactive in this reaction

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• cleavage of the methoxyphenyl group in aqueous methanol using excess of ceric ammonium nitrate (CAN) as a soft oxidant (Scheme 14). The sequence afforded the target (S)-homoallylic amine 69 in 64% overall yield with a complete retention of chirality. To gain a mechanistic insight into the formation of the

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• iminoiodinanes for the metal-free aziridination of unactivated olefins. 1H NMR and cyclic voltammetry (CV) studies indicate that hydrogen-bonding between HFIP and the iminoiodinane generates an oxidant capable of direct NGT to unactivated olefins. Stereochemical scrambling during aziridination of 1,2

• catalysts or photochemical procedures have been developed to enable this transformation [7][8][9]. The reactivity of hypervalent iodine reagents can be enhanced via Lewis acid catalysis [10]. For example, PIDA becomes a stronger oxidant upon coordination of BF3·OEt2, enabling chemistry that was not

• consistent with H-bonding between HFIP and 2c, which results in a more potent oxidant and gives rise to the observed HFIP-promoted olefin aziridination chemistry. A number of observations are relevant to the mechanism by which unactivated olefin aziridination is accomplished by the HFIP-activated

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• properties such as anticancer, anti-HIV protease, anti-ageing, anti-inflammatory and anti-oxidant, to name a few [12][13][14][15][16][17][18][19][20][21][22][23]. Considering the fact that curcumin’s uniqueness is associated with its ability to function as a multifunctional substrate in various organic

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

• readily available hydrazones under mild, safe and oxidant-free reaction conditions. This review presents a comprehensive overview of oxidative electrosynthetic transformations of hydrazones. It includes the construction of azacycles, the C(sp2)−H functionalization of aldehyde-derived hydrazones and the

• 4-methylbenzaldehyde-derived hydrazone = 0.89 V vs Ag/AgCl in CH3CN and Ep/2 of diphenylphosphine oxide > 0.89 V vs Ag/AgCl in CH3CN) (Scheme 22) [70]. Similar yields were previously obtained for the same transformation using a substoichiometric amount of potassium persulfate as oxidant [71]. In

• hydrazone through the in situ generation of iodonium as oxidant while the latter would facilitate the deprotonation of iodoammonium 162 and the elimination of HI from N-iodo intermediate 163. The best yields were obtained with aromatic ketone-derived hydrazones (Scheme 33) [83]. Conclusion Given the rich

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• peracetic acid as a terminal oxidant [20]. Recently, Kočovský et al. disclosed a method employing 2-methylbenzamide and benzonitrile to yield 3-aryl-substituted isoquinolinone derivatives in the presence of n-butyllithium [21]. On the other hand, the intramolecular oxidative cyclization is also a viable

• ) diacetate (PIDA) [22][23]. And more recently, Du and our group have developed a method for the chemoselective cycloisomerization of o-alkenylbenzamides to 3-arylisoquinolinones, using PhIO as oxidant in combination with a catalytic amount of trimethylsilyl trifluoromethanesulfonate [24]. Although

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• -pyridine substituted diarylamines, either using bis(trifluoroacetoxy)iodobenzene as an oxidant, or electrochemically, via potentiostatic oxidation. Electrochemical synthesis occurs under mild conditions; no chemical reagents are required except electric current. Both approaches can be considered as a late

• salts. The oxidative behavior of substituted diarylamines is known to be very diverse and strongly influenced by the substituents in the phenyl rings as well as by the type of the oxidant. Diarylamines can serve as precursors for a wide variety of practically useful compounds such as diarylnitroxides

• containing electron-donating and electron-withdrawing groups were taken as the starting compounds (Scheme 2). As an oxidant, bis(trifluoroacetoxy)iodobenzene (PIFA) was used. It allowed obtaining the targeted heterocyclic cations in practical 49–54% yield for all starting diarylamines. Notably, a minor

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• into pentacycles 67. The same products were obtained when CoBr2 was used as external oxidant in the one-pot cascade reaction (Scheme 24, conditions b). No substantial improvement in the yields of 67 and 69 was observed when the synthesis was carried out in two steps, performing the GBB reaction under

• inert atmosphere and oxidizing 64 in the presence of CoBr2 (Scheme 24, conditions c and d; one-pot: 10–43%, two steps: 11–37% yields). Interestingly, polycycles 69 were formed when I2 was employed as the oxidant (Scheme 24, conditions e), which was presumably due to the coordination between the oxidant

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• optimized conditions, revealing the tetrazole-substituted iodane 1a to be the best oxidant for this reaction (Table 2). The two suitable methods (A: HCl in EtOAc; B: TBACl in MeCN) were then applied to a variety of activated alcohols. The best option is shown in Figure 5. Model substrate 4a could be

• was investigated, potentially leading to the formation of a hydroxy(chloro)iodane intermediate. This intermediate either liberates hypochlorous acid as the terminal oxidant or undergoes a direct ligand exchange with the alcohol, followed by oxidative elimination to form the aldehyde. Thus, these

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• membranes to ensure a high proton conduction or leading to an efficient reaction production of hydrogen and oxygen gases, with no risk of electrolyte leakage and restricted gas-crossover [15][16][17]. Also, besides their conductivity and their low permeability to fuel and oxidant, the chemical and