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

• ]. Based on this result, the implication of intermediate C in the reaction mechanism was demonstrated. However, an alternative pathway from intermediate A to the propargylamine product has been proposed when copper is used as the catalyst. In this case, the activation of the C–X bond of the dihaloalkane

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• conditions: 1c (1 mmol, 0.30 g), hydroxylamine hydrochloride (1.2 mmol, 0.08 g), EtOH (5 mL). Proposed reaction mechanism. Synthesis of product 13. Reaction conditions: 8o (1 mmol, 0.37 g), pivaloyl chloride (3 mmol, 0.36 g), MeCN (5 mL). Optimization of the reaction conditionsa. Supporting Information

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• present reaction, and products 17l and 17m were isolated in high yields with moderate to high stereoselectivities. The plausible reaction mechanism is shown in Figure 3. First, the removal of the acidic proton of the pre-nucleophile by potassium carbonate to form intermediate I, which undergoes cation

• -amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the catalytic Mannich reaction. Further investigations into the reaction mechanism and product applications are ongoing in our group. Selected examples and applications of chiral halogen-bonding catalysts. Selected examples

• for the construction of contiguous tetrasubstituted carbon centers via the Mannich reaction and this work. Plausible reaction mechanism. Catalyst screening for the asymmetric Mannich reaction. All yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. N

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• improving the substrate scope and understanding the reaction mechanism are in progress in our laboratory. Synthesis of cyclic diarylbromonium compounds. Substrate scope. Reactions were performed on a 0.15 mmol scale. Yields were determined by 1H NMR spectroscopy of the reaction mixture using 1,2,3,4

• : Representative jp vs v0.5 slope values for oxidation of Martin’s bromane precursor 6 (ref. [17]). D: Plausible reaction mechanism. Optimization of electrochemical oxidation/cyclization conditions.a Supporting Information Crystallographic data for the structure reported in this paper have been deposited with the

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• excess of quinone 3 leads to the formation of 2-(indolin-2-yl)-4,5,6,7-tetrachloro-1,3-tropolones 8a,b as final products. The detailed reaction mechanism in acetic acid solution was studied by the PBE0/6-311+G(d,p) method on the example of the interaction of 2-methylquinolines and 2-methylbenzazoles with

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• has an E,E,E-configuration, while the compound 8a has a Z,E,E-configuration. On the basis of the above experiments and the previously published results [42][43][44][45][46][47][48][49][50][51][52], a plausible reaction mechanism was proposed in Scheme 4 to explain the formation of the various oxindole

• ), CH3CN (5.0 mL), rt, 2 h; yields refer to isolated yields. Proposed reaction mechanism for the various compounds. Optimization of reaction conditions.a Dimerization of MBH carbonates of isatins.a Supporting Information The crystallographic data of compounds 5a (CCDC 2390713), 5j (CCDC 2390714), 6e (CCDC

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

• 120 °C for 12 h; yield based on 3. Gram-scale synthesis of 2a and 4a and one-pot synthesis of 4a. Control experiments. Plausible reaction mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 110: Experimental procedures, compound characterization data

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

• mixture, which significantly impeded the progress of the desired reaction. Therefore, on the basis of the above experimental results and previous reports [21][27][28][29][30], we proposed a possible reaction mechanism (Scheme 3b), taking CF2HCOOH as the illustrative example. Initially, a double ligand

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• theory (DFT) calculations, a proposed reaction mechanism is suggested as shown in Figure 3. Initially, copper acetylide INT-11 is formed by the reaction of acetylene with a copper precatalyst, leading to the formation of an N-acyl nitrene acetylide intermediate INT-12 after the incorporation of

• late-stage functionalizations of complex scaffolds such as peptides, drug molecules, and natural products containing unprotected free OH and NH groups are anticipated. Proposed reaction pathway for the copper-catalyzed synthesis of δ-lactams from dioxazolones. Proposed reaction mechanism for the copper

• -catalyzed synthesis of 1,2,4-triazole analogues from dioxazolones and N-iminoquinolinium ylides. Proposed reaction mechanism for the copper(I)-catalyzed synthesis of N-acyl amidines. Proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones. Proposed reaction pathway for

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

• . According to the reaction mechanism outlined in Figure 12, the copper catalyst reacts with an azide ion to generate a Cu(II)–N3 complex 60, which is then anodically oxidized to the Cu(III)–N3 complex 61. The Cu(III)–N3 complex 61 releases the azidyl radical 62 from the azide ion 58, returning it to the Cu

• enantio-determining transition states. Based on the mechanistic studies, a reaction mechanism is proposed in Figure 14. First, the in situ-generated Cu(I)–CN complex 83 is oxidized at the anode to form a Cu(II)–CN complex 84, which reacts with diarylphosphine oxide 80 to generate a transient P-centered

• –Lam coupling. The reaction mechanism is illustrated in Figure 19. During the reaction, the unstable Cu(I) species 121 is reduced to Cu(0) at the cathode and is plated to suppress side reactions. After 10 minutes, when the current is inverted, the copper that previously precipitated as an impure film

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

• behavior or reactivity properties. The ambiguity related to the role of Cu(OTf)2 is particularly relevant for cycloaddition reactions, where it is even more difficult to justify the activation of the copper species as a Lewis acid or metal catalyst [12][13][14]. The reaction mechanism involved can be ionic

• compounds catalyzed by copper triflate under ultrasound irradiation allowed the one-pot formation of 1H-benzo[f]chromen-2-yl(phenyl)methanones (naphthopyranes) 37. The comparison with conventional method showed better yields and shorter reaction times. The suggested reaction mechanism showed the formation

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

• ) annulation of enals with ynamides 8 to afford axially chiral 7-arylindolines 9 was reported [20]. The reaction mechanism, rationalized by DFT calculations, is believed to occur through catalyst C3 activation of the substrate 8, dehydration, and deprotonation with tautomerization leading to the enamine

• , previous findings from the literature, and experimental results, a reaction mechanism was proposed [46]. Hydrogen bonding as well as π–π interaction with the catalyst (R)-C22 activates both substrates in the stable intermediate Int-35. This stabilized state ensures the concerted control of

• ). The reaction mechanism proposed by the authors was analogous to that of the aforementioned atroposelective Friedländer reaction. Outstanding yields and enantioselectivities were accomplished during the substrate scope screening as well as in a model gram-scale reaction (83%, 91% ee). Annulation of

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• from the simultaneous formation of sulfinamide 6ea also isolated in this reaction for the first time (both in trace amounts). Reaction mechanism The inability to detect sulfinamide 6 and the isolation of sulfonamide 5, along with other byproducts (3, 4, and 7), stimulated us to propose a plausible

• reaction mechanism that would support both the obtained yields and the formation of unexpected species. As mentioned above, the presence of light influences the reaction outcome. When the reaction was carried out in the absence of light, only 4a, 3a, and 7a were isolated (under these conditions, there was

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• except for azadienes bearing a bulky t-Bu substituent, which led to the Michael product 27e’ albeit with low stereoselectivity. The authors proposed a plausible reaction mechanism to explain the observed stereoselectivity of the reaction. Firstly, the isocyanoacetate is deprotonated by the tertiary amine

• excellent enantioselectivities (97–99% ee) using also chiral phosphoric acid XIV (Scheme 17). The authors proposed a reaction mechanism in order to explain the observed stereoselectivity of the products in which through hydrogen bonding the chiral phosphoric acid provides a chiral environment where the

• SPINOL-derived phosphoric acid XVI provided the best enantioselectivities (Scheme 18). In both reactions, it was necessary to add acid-washed molecular sieves (AW-MS) in the reaction medium. The proposed reaction mechanism based on the mechanistic experiments and previous reports is depicted in Scheme 19

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

• good yields, demonstrating the scope of the reaction. The authors proposed an alternative reaction mechanism to those already described, in which trans-aminopalladation of the alkene, mediated by Pd(II), occurs with intramolecular attack of the nitrogen on the terminal carbon, generating a 6-membered

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

• one remaining –NH group is catalytically active while both tri- and tetraalkylated analogues 40 and 41, without an –NH unit, are not. Further, the authors performed 1H NMR experiments with a different substrate:macrocycle ratio and suggested a bifunctional reaction mechanism involving both inner amine

• concluded that both the presence of hydrogen-bond donor moieties (pyrrolic –NH groups) and a basic β-substituent are necessary to make the compound catalytically active. Further, authors have performed 1H NMR binding and kinetic studies and suggested that the reaction mechanism involves a simultaneous

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• chemistry and optical science. A plausible reaction mechanism for the formation of the target molecules 18a–n via a high-order multicomponent reaction is shown in Scheme 3 and consists of two processes: an Ugi-azide reaction and a Pd/Cu-catalyzed heteroannulation reaction. The Ugi-azide reaction mechanism

• the 1,5-disubstituted tetrazole-indole system and our synthetic approach. High-order multicomponent reaction for the synthesis of 1,5-disubstituted tetrazol-methanesulfonylindole hybrids. Plausible reaction mechanism for the synthesis of target molecules 18a–n. Supporting Information Supporting

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

• -scale syntheses demonstrated that the protocol is practical and useful for preparation of the γ-carbonyl peroxides. The authors propose the following reaction mechanism: initially Co(II) is oxidized by TBHP to form Co(III)OH and the tert-butoxy radical. In result of ligand exchange with TBHP or acetic

• reaction mechanism includes the formation of α-dicarbonyl compound A and elimination of CO which results in aldehyde B. tert-Butoxy E and tert-butylperoxy F radicals are formed during the redox Cu(I)/Cu(II) cycle. The acyl radical C generated via hydrogen atom abstraction with tert-butoxy radical E adds to

• reaction mechanism was proposed as an anchored ionic type pathway, rather than the free radical one. First, the Togni reagent forms complex A with the dinuclear paddle-wheel copper nodes of Cu3(BTC)2. Complex A then adds to styrene 175 to form iodonium cation B, which is converted to intermediate D by

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

• presence of fluorine and a newly installed electron-deficient aryl group on α-carbon which increases electrophilicity of the α-carbon center [55]. The proposed reaction mechanism (Scheme 2) begins with the formation of one of two potential iodine intermediates, labeled as I or II. These intermediates arise

• absence of a base. Additionally, the presence of 40 equivalents of water proved to be crucial for the reaction, as altering the amount of water significantly impacted the product yield, indicating the importance of water in the reaction mechanism. A diverse range of functionalized diaryliodonium salts

• mechanism by adding 2 equivalents of TEMPO to the reaction mixture. The absence of the desired product indicated the involvement of a radical pathway in the process. The proposed reaction mechanism begins with the activation of eosin Y by visible light from 5 W blue LEDs, transitioning it to its excited

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• ]-proton shift reaction in this study is expected to proceed via the reaction mechanism reported by Soloshonok [25][26][27][28][29][30][31][32], as shown in Scheme 6. First, DBU interacts with the benzylic hydrogen of the imine (R)-16, and this hydrogen is about to be abstracted as a proton. This hydrogen

• reaction mechanism. Investigation of the reaction conditions. Supporting Information Supporting Information File 3: Full experimental details, 1H, 13C, 19F NMR spectra of 16a–g and 23a–g, and HPLC charts of racemic as well as chiral compounds 23a–g. Supporting Information File 4: Crystallographic

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• ethynylethylene carbonates as the starting materials, thus completing their enantioselective formal [4 + 1] cycloadditions with cyclic 1,3-dicarbonyl compounds (Scheme 36, 34a–k). They speculated that in the reaction mechanism, the key step is the formation of the copper vinyl allenylidene intermediate from vinyl

• . Through control experiment, they have proposed a reaction mechanism where the formation of copper vinyl allenylidene and Conia-ene reaction are pivotal steps in the process (Scheme 48). Crafting atropisomers, particularly for those with 1,2-diaxes, poses a formidable task owing to the intricate interplay

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

• . Repeating the reaction on 500 mg for a longer reaction time a notable 68% isolated yield of 3d was obtained (Table 3, entry 2). These slightly different conditions were applied to the gram scale synthesis of 3a obtaining good results (Table 3, entry 3). To obtain some information of the reaction mechanism

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• -dioxane/water 5:1, 100 °C, 1 h. Scope and isolated yields of the synthesis of 5. Reaction conditions: 4 (1 equiv), p-TsOH·H2O (20 equiv), toluene, 100 °C, 4 h. Proposed reaction mechanism of the cyclisation with N,N-dimethylanilino functional groups. Optimization of the synthesis of 5a. Photophysical data

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• proceeded well only in solvents which can produce hydroperoxides in situ, we hypothesized that hydroperoxides have a pivotal role in the reaction mechanism. In order to confirm that the reaction proceeds through a radical mechanism, the decarbonylation–oxidation reaction of 3ba was performed in the presence

• insertion of the hydroperoxide into the substrate leading to the decrease in the –O–OH peak. An increase in the peak at δ 9.6 ppm indicated the formation of a phenolic moiety over time. Based on these observations, a plausible reaction mechanism is proposed (Figure 5). Proton abstraction followed by

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

• not increase the yield of pyridine 11 further (Table 2). Despite the numerous works in the field of peroxydisulfate oxidation, there is still no unified view of the reaction mechanism. Consequently, in [31], the assumption of an electrophilic substitution mechanism for the Elbs and Boyland–Sims

• the amino group is involved in the formation of an intermediate hydroxylamine derivative. Scheme 3 demonstrates a possible reaction mechanism using the example of the peroxydisulfate oxidation of MU and TMU catalyzed by PcM. It is proposed that PcM provides the necessary polarization of peroxydi(mono