A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• thiophene to reduce the diene's reactivity or altering the electrophilicity of the dienophile. Based on the computational analysis of the transition states, reaction mechanisms for the IMDA and the dehydration re-aromatization process are proposed in Scheme 5. In the IMDA reaction for the preparation of

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

• these derivatives, this study aims to offer direct synthetic guidance and important insights into the rational design of novel cinnamate molecules with promising potential as future drug candidates. The reaction mechanisms will be discussed briefly. 2 Carboxyl group functionalization 2.1 O/N-acylations

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• substrates, both dicarbonylation and monocarbonylation processes occurred simultaneously with Cu(OAc)2, favoring the dicarbonylation process. In contrast, using CuBr(Me2S) the monocarbonylation process was favored. Possible reaction mechanisms: First, CO coordinates with copper salts to form (carbonyl)copper

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

• medium or lead to the formation of the same final product as that achieved with formaldehyde, but through different reaction mechanisms. Due to the importance of this research, this review aims to summarize and analyze the significant efforts made in this regard in recent years. Major emphasis will be

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

• , and benzamide, however, no relevant competitive oxidation peak was observed with only Cu(OAc)2. These results indicate that Cu(II) intermediate 5 was generated. Based on the mechanistic studies, the authors suggested plausible reaction mechanisms (Figure 4). First, the Cu(II) catalyst coordinates with

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• -mediated and SN2 reaction mechanisms. Ultimately, the nudged elastic band climbing image (NEB-CI) method predicted the SN2 pathway to be favoured, and transition state optimization showed this to possess a Gibbs free energy of activation of 24.3 kcal/mol. This report shows the ease with which sulfoxonium

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

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• , Suzuki–Miyaura and Sonogashira cross-coupling with 1 has a broad substrate scope and can be used to synthesize various fluoroalkenes 2 and fluoroenyne 3. We speculate that these reaction mechanisms were similar to general cross-coupling mechanisms [45][46]. Conclusion We used Suzuki–Miyaura and

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

• extensive effort. This involves complex parameter optimization, meticulous validation against experimental data, and careful consideration of diverse reaction conditions and possible reaction mechanisms [28][29]. Although some studies employ transition-state (TS) theory to simulate activation energies and

• reaction mechanisms. These models are particularly valuable in areas where experimental data are sparse or challenging to obtain, thereby extending the range of ML applications in chemistry. Educating the next generation of chemists, engineers, and data scientists in both ML and chemical synthesis is

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• the N1-pathway by a product ratio of 4.5:1, which supports a pathway producing the observed experimental N2-product ratios with greater than 80% yield. The N1-product was again found to be lower in energy by 4.4 kcal/mol than the N2-product. To further explore whether the reaction mechanisms followed

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

• reagents offer a viable alternative to traditional aryl-λ5-iodane-based oxidants, although further studies are necessary to fully understand their reaction mechanisms. Experimental General procedure for oxidation of benzylic alcohols 1a (700 µmol, 201 mg, 1.40 equiv), benzylic alcohol (3, 500 µmol, 1.00

• ) in MeCN (2.5 mL), respectively, were stirred at 60 °C for 2.5 h and quenched with Me2S (1.40 mmol). Possible reaction mechanisms via the formation of a) a Cl(I) species and b) the formation of an alkoxyiodane IIb. Both are initialized by the activated iodane I-OH, which was observed as c) I-OMe

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• energy than our proposed species. The reaction mechanisms are described in detail in this work and were found to be in excellent agreement with the experimental yield. These initial results confirmed that our proposed mechanism was energetically favored and therefore more plausible compared to

• reactions, we explored different pathways of the reaction mechanisms for the ortho-halogenation using 2-naphthol as a model substrate (Scheme 2). In such a way, we found a reaction pathway that was energetically favored. Based on our successful procedure for chlorination, we also developed an efficient

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• of novel synthetic strategies. It has expanded the scope of available synthetic methods and contributed to the synthesis of complex molecules with high efficiency and selectivity. Ongoing research in this field continues to explore new catalysts, photosensitizers, and reaction mechanisms to further

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• )/TMSCl in the presence of CO. The reaction, again, ends with an N-cyclization giving the N-aroylindoles with fair to good isolated yields. The reaction mechanisms are reported in Scheme 23. Synthesis of indoles by Rh-catalyzed carbonylation reactions In the past, Tang and co-workers, demonstrated that

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• +) reference couple. Working electrode: Pt, counter electrode: Pt, reference electrode: Ag/Ag+ in acetonitrile, solvent: o-dichlorobenzene, supporting electrolyte: 50 mM TBAPF6. Reaction mechanisms of thermal and photoinduced [2 + 2] cycloaddition on C60 [19][22][23]. Thermal [2 + 2] reaction of Li+@C60 TFSI

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• singlet state [10]. Although only a few analyses of the reaction mechanisms have been studied due to the complexity of the system, several intermediates inside the CNT have been proposed [3][11][12], which may be different from those proposed to take place in the gas phase or in the solid state at high

• pressures and high temperatures [13][14][15]. We aim to shed light in these reaction mechanisms and energy profiles by using complementary methodologies as standard density functional theory (DFT) calculations and first-principles Car–Parrinello molecular dynamics (CPMD) simulations. Firstly, we have

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• -iodobenzyl chloride. Reaction mechanisms for the reactions of dimeric reductants (D2) such as (Y-DMBI)2 derivatives with acceptors (A) such as organic semiconductors or, in this work, organic halides that react further (the relative rates of steps are indicated for cases where the A reduction potential falls

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• advancements in the iodide/phosphine catalytic photoredox system. The primary focus of the paper is to delve into the unique catalytic reactivity exhibited by the iodide/phosphine photoredox system, while also exploring potential reaction mechanisms. It is mainly organized around different types of reactions

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• . Several terpene cyclizations with an exomethylene group are known, such as with caryolene and crotinsulidane diterpenoids, and the reaction mechanisms have been analyzed [27][28][29][30]. It would be interesting to see how the exomethylene group reacts in the cyclization of variexenol B. In this study, we

• follow similar reaction mechanisms, however, when comparing path a and path b, the most striking energy difference is in the step from IM2a/b to IM3a/b (Figure 2B). The energy barrier of this step is 6.3 kcal/mol for path a, whereas 13.6 kcal/mol for path b, with a difference of 7.3 kcal/mol. Although

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• is no need to use a metal catalyst, base, or additive. N-(Sulfenyl)succinimide/phthalimide acted as an active electrophilic sulfur source, acted in the reaction mechanisms. However, mechanistic studies need further exploration to define a valid reaction pathway. Therefore, we believe that the use of

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• , electrophilic properties of atom C3 should be mainly explained by orbital factors, rather than charge ones. Summarizing the data obtained during the synthesis of indanones 3 (Scheme 5, Scheme 6 and Table 1), NMR, and DFT studies on intermediate cations (Table 2 and Table 3), one may propose plausible reaction

• mechanisms for the cyclization of compounds 1 and 2 into indanones 3 in TfOH (Scheme 7). Protonation of the carbonyl oxygen of enone 2 gives rise to cation B which is followed by cyclization into indanone 3 through mesomeric form B'. The hydroxy ketone 1 is protonated at the oxygen atoms leading to cation A

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• potent and significant drugs containing imidazole moieties. The formation of imidazole derivatives can be achieved using imidazole N-oxide as starting material. In this review, the scope of substrates and reaction mechanisms of various synthetic approaches using imidazole N-oxides as substrates are

• is a new emerging research area and which offers a lot of room for further development. In this review, several research procedures were discussed with their substrate scope and proposed reaction mechanisms. We hope that this review can be helpful to the researchers and the chemists for the future

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• macromolecular electrochemistry. The scope of this interdisciplinary issue ranges from synthetic aspects (such as electrosynthesis and reaction mechanisms) to materials science (including redox properties and devices). Shinsuke Inagi and Mahito Atobe Yokohama, October 2022