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

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

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

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• : 3a (1 mmol), CDI (0.49 g, 3 mmol), DBU (0.17 g, 1.1 mmol), MeCN (7 mL). Proposed reaction mechanism for the formation of products 4. Synthesis of derivatization products 7 and 9. Optimization of the reaction conditionsa. Supporting Information Supporting Information File 141: General information

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

• , due to the protonation of triticonazole, the participation of the protonated form in the overall reaction mechanism is also considered in pathway B (Scheme 21). Benzo[c][1,2]oxazines are useful scaffolds for the synthesis of natural products. In 2021, the Han group developed the electrochemical [4 + 2

• leelamine, racemorphan, and analogs of sertraline and celecoxib was achieved with yields ranging from 40% to 92%. The reaction mechanism begins with the photoexcitation of the intermediate [TAC2+•]*, which oxidizes the arene substrate to form a cation radical. This radical is deprotonated and then further

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• mapping (AAM) is a process that establishes the correspondence between atoms before and after a reaction, reflecting the reaction mechanism. AAM-exempted methods [145][146][147][148][149][150] apply graph convolutions to each reactant and product molecule separately, and then use a pooling function or

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• translated to the formation of other macrocycles as long as they share a similar reaction mechanism. (a) Control experiment testing deiodination of 2-iodoresorcinol. (b) Molecular crystal structure of chlorinated resorcin[4]arenes 1h and 1i, and carboxylic acid-containing 1s at 100 K. Thermal ellipsoids are

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

• cyclization occurred by producing trans-15 in 35% yield as the single diastereoisomer. For the reaction mechanism, we propose a mechanistic hypothesis according to the study by Nicewicz and Nguyen (Figure 3) [23]. The incorporation of electron-donating groups into the acridinium core, as in catalyst IV

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• additionally confirmed by X-ray diffraction (see Supporting Information File 1 for details) (Figure 2). To confirm the reaction mechanism, we performed diazotization followed by azo coupling of amide 2a using labeled Na15NO2 as the nitrosating reagent (Scheme 4). As a result, 15N-labeled triazinone 8 was

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

• give rise to epoxidation products. Epoxides are not on-path to the observed aziridines. f) Proposed reaction mechanism. Optimization of HFIP-promoted aziridination of cyclohexene (1a). Conditions: 0.20 mmol 1a, 0.40 mmol PhINTs 2a, 1.0 mL HFIP, N2 atmosphere, 20 °C, 16 h. Yield was determined via 1H

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• the ML model by being considered as a nucleophile or electrophile, depending on the reaction mechanism. Descriptors allowed for the inclusion of a variety of co-catalysts, ranging from Fe-piano stool complexes to copper complexes. The consideration of co-catalysis into model development further

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• electricity was passed to the solution. A plausible reaction mechanism for the current reactions is described in Scheme 3. The reaction of carbon–carbon triple bonds and H+ species, which are derived from the Brønsted acid (in method A) or EGA (in method B), gives the vinylic carbocation intermediate A, which

• for 2a. Plausible reaction mechanism. Optimization of the gem-difluorination of hex-5-yn-1-ylbenzene (1a) to form difluorinated compound 2a (method A). Scope and limitations. Supporting Information Supporting Information File 84: Experimental procedure, characterization data of compounds and copies

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• substituents has a lower Ea than DBA with electron-donating substituents. DFT calculations The reaction mechanism was investigated by computational calculations. The reaction mechanism between 5 and benzyl azide was supported by the ωB97X-D/6-31G(d,p) calculations with the CH2Cl2 polarizable continuum model

• . (a) Strain-promoted azide–alkyne cycloaddition between DBA 5 and benzyl azide and (b) 1H NMR spectral change at 30 °C in CDCl3. Arrhenius plots of the rate constants for the reaction between 5 and benzyl azide in CDCl3. Proposed reaction mechanism for the formation of compound 6a. Free energy

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

• reported in due course. Biologically active derivatives of cyclohexanones. X-ray structure of 4a (CCDC 2351387). Origin of stereoselectivity in the double Michael addition. The Michael donor–acceptor reactivity of curcumin: previous vs present work. A plausible reaction mechanism. Scale-up reaction