New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• yields. The studied tandem Ugi and intramolecular Diels–Alder reactions allow high substituent variation in the named isoindoles. Keywords: 1,3-butadienylfuran; furo[2,3-f]isoindole; intramolecular Diels–Alder reaction; isoindole; one-pot; Ugi reaction; vinylfuran; Introduction Energy-saving and

• construction [27][28]. For instance, the intramolecular Diels–Alder reactions of vinylarenes (IMDAV) strategy [29][30] has been used to synthesize annulated isoindoles, including thieno[2,3-f]isoindoles [31][32] and furo[2,3-f]isoindoles [33][34], from thienyl- or furylallylamines and unsaturated acid

• agree with our previous results on tandem acylation/Diels–Alder reactions [31][32][33] and lead us to conclude that the final Diels–Alder reaction products are formed as the exo-adducts. Moreover, since we do not observe other stereoisomers we speculate that the Ugi and Diels–Alder reactions occur under

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• ), 115.0, 85.6, 39.3, 37.8, 27.4; HRMS–ESI+ (m/z): [M + H]+ calcd for C21H19O2, 303.1380; found, 303.1383. Equipment for carrying out reactions by the diffusion mixing method. Knoevenagel and Diels–Alder reactions in the multicomponent synthesis of substituted cyclohexadienes under formaldehyde

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

• insights were outlined as well as cycloaddition and aza-Diels–Alder reactions were included. These strategies have gained attention due to their highly atom- and step-economy, one-step multi-bond forming, mild reaction conditions, low cost and easy handling. Keywords: cascade process; copper catalysis

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

• , respectively. Additionally, the most common cyclic α,β-unsaturated imines involve benzofuran or saccharin-derived azadienes (Figure 1). Cycloaddition reactions, especially Diels–Alder reactions, have attracted a lot of attention since their discovery as one of the most powerful methodologies for the

• dienophile, and therefore it proceeds through the reaction of electron-poor dienes and electron-rich dienophiles (Figure 2b). α,β-Unsaturated imines can undergo inverse electron demand aza-Diels–Alder reactions (IEDADA) to produce N-heterocyclic compounds. The search for an enantioselective pathway to carry

• -unsaturated imines and variety of structures. The hetero-Diels–Alder and inverse electron demand hetero-Diels–Alder reactions. Different strategies to promote the activation of dienes and dienophiles in IEDADA reactions. Examples of non-covalent interactions in organocatalysis. Structure of a cinchona

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

• intermolecular Diels–Alder reactions with 34 or other dienophiles, leading to a diverse array of bisorbicillinoids. Based on the crystal structure of TropB, a homologous enzyme of SorbC, Narayan and co-workers have intensively elucidated that the detailed mechanisms of the oxidative dearomatization catalyzed by

• synthesized 33 generated the highly reactive intermediate 34 in aqueous solvents under mild conditions [37][42]. In this process, the co-solvent (cs) allowed control of the dimerization modes via either Michael addition or Diels–Alder reactions, facilitating the systematic total synthesis of the

• tolerance through enzyme mutagenesis should allow more precise control over scaffold-constructing reactions. As with the related natural products, hybrid sorbicillinoids were also known to be biosynthesized through Diels–Alder reactions between diene 34 and non-sorbicillinoid-derived dienophiles [29

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• Ayhan Yildirim Department of Chemistry, Bursa Uludağ University, Bursa 16059, Turkey 10.3762/bjoc.20.114 Abstract Tandem Diels–Alder reactions are often used for the straightforward formation of complex natural compounds and the fused polycyclic systems contained in their precursors. In the

• Diels–Alder reactions and can be used repeatedly without significant degradation. These materials also allow the reaction to be completed in less time, with less energy consumption and higher yields. Keywords: biobased solvent; epoxyisoindoles; furanics; green chemistry; intramolecular Diels–Alder

• trying to make the conditions for Diels–Alder reactions more environmentally friendly [48][49][50][51][52][53][54][55][56][57][58]. However, the number and variety of substrates in these studies is often limited, deep eutectic solvents are required and it is difficult to achieve both satisfactory product

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• unreactive. Specifically, breaking their aromaticity, which is required for the Diels–Alder reaction to occur, is unfavorable and results in Diels–Alder reactions with furans often being easily reversible [18]. Fortunately, although difficult, it is not impossible to perform a Diels–Alder reaction with

• furans. While the frontier molecular orbital theory can be applied to this cycloaddition reaction, the thermodynamics must also be taken into consideration. Most Diels–Alder reactions with furans as the diene follow normal-electron-demand with the diene HOMO reacting with the dienophile LUMO due to the

• determined that a ratio of 1:1 MeOH/H2O should be used as this solubilized the chemical probe most efficiently. Additionally, others have previously noted that polar solvents tend to benefit Diels–Alder reactions between furoic acids and maleimides [19][23]. Next, we looked at how different additives would

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

• accelerated 1,3-dipolar and Diels–Alder reactions [12][13], it is noteworthy that the anticipated diverse properties resulting from the derivatization of Li+@C60 have not yet been fully realized. To further leverage the unique properties of the novel ion-endohedral fullerene, achieving diverse property tuning

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• pristine acene with a dienophile to transiently form a cycloadduct with increased solubility for processing purposes, and unmasking it afterwards via a retro-Diels–Alder reaction [16][17][18][19]. In parallel to retro-Diels–Alder reactions, another efficient strategy for the in situ aromatization of target

• π-CPCs relies on the extrusion of carbon monoxide (CO) from soluble precursors incorporating bridging ketone fragment(s). In contrast with the thermal activation required in retro-Diels–Alder reactions, photoirradiation of α-diketones triggers a Strating–Zwanenburg decarbonylation leading to the

• group-16 heteropines was successfully implemented as a key step in the fabrication of devices with highly promising properties. Elimination of chalcogen fragments coupled to ring contraction thus appears as a powerful synthetic tool to complement retro-Diels–Alder reactions and decarbonylations widely

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• –Alder reactions (Scheme 5). Furthermore, the researchers conducted a comprehensive investigation into the optical and electrochemical characteristics of these compounds. The key component employed in the production process, known as 3,4-bis(methylene)cyclobutene, was generated through the application of

• of POA 21. This POA featured an extended conjugation and was obtained in 30% yield. In a study released by Swager and Parkhurst in 2012 [36], the term POA has been used for the first time in the literature. In this study, they successfully synthesized POAs 25a and 25b by employing sequential Diels

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• introduced in 2017, followed by carbon nanotubes in 2019. Consistent with expectations from theory, anion–π catalysis on carbon allotropes generally increases with polarizability. Realized examples reach from enolate addition chemistry to asymmetric Diels–Alder reactions and autocatalytic ether cyclizations

• . Currently, anion–π catalysis on carbon allotropes gains momentum because the combination with electric-field-assisted catalysis promises transformative impact on organic synthesis. Keywords: anion–π interactions; autocatalysis; catalysis; carbon nanotubes; Diels–Alder reactions; electric-field-induced

• catalyst 21 was applied to other reactions. Diels–Alder reactions are of special interest for anion–π catalysis because of the promise to accelerate an intrinsically disfavored but relevant pathway, like in the benchmark enolate addition (Figure 2) [62]. Namely, in solution, the endo transition state VI is

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• materials and the conditions used [5]. Some common types of TCRs include Diels–Alder reactions [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], photocycloadditions [21][22][23][24][25][26][27][28], and other types of multistep cycloadditions [29]. Steric hindrance can have a significant effect on

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• –Alder reactions. DIA TFA: diisopropylammonium trifluoroacetate. Supporting Information Supporting Information File 8: Numbering scheme, experimental procedures, 1H, 13C and 2D NMR spectra, and mass spectra. Acknowledgements We thank Serdar Dilek for technical assistance and Miguel Vences for fruitful

• ), diisopropylamine (0.4 equiv), TFA (0.1 equiv), THF, reflux, 3 d, ii) maleic anhydride (1.2 equiv), reflux, 16 h; d) MeMgBr (3.0 equiv), THF, reflux, 4 h. Screening of different reaction conditions with the (S)-Jørgensen’s organocatalyst S-16 for the key Domino reaction, consecutive Mannich and intramolecular Diels

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• , including cross-coupling-type chemistries on a conformationally stable cis-vinyl zinc building block. 3 Diels–Alder reactivity of 1,4-dithiin-based dienophiles and dienes Vinyl sulfones and vinyl sulfoxides are classical synthetic equivalents of ethylene in Diels–Alder reactions, and have been widely used

• acetylenes in Diels–Alder reactions [49], since desulfonylation of the cyclohexene-disulfones with sodium amalgam or samarium(II) iodide affords 1,4-cyclohexadienes (Scheme 8). In a comparative study by Nakayama [50], the dithiin-type cyclic disulfone 7 emerged as a much stronger dienophile than any other

• helpful when dealing with sensitive dienes. A nice illustration of this is afforded by De Lucchi’s simple synthesis of barrelene (33) from oxepin (29, Scheme 8b) [52]. Oxepin’s equally unstable valence tautomer 30 (benzene oxide) is quite reactive as a diene in Diels–Alder reactions, and can react with 7

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• organocatalysis in general. Examples of typical reaction types for redox-neutral asymmetric organocatalysis are aldol reactions [13], Michael reactions [14][15][16], and Diels–Alder reactions [17][18]. The processes associated with changing oxidation states of atoms in substrates thus can be named “redox

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• reported extensive studies on the regio-and stereoselectivity of nitroso Diels–Alder reactions between various nitroso derivatives and functionalized dienes [23]. These studies led to the selection of enol phosphates as ketone precursors for the diene functionalization. Enol phosphates display several

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• dienophiles and undergo Diels–Alder reactions with 1,3-dienes. However, the dienophilic reactivity is affected by the nature of the substituent groups on the two sides of the σ2,λ3-P atom and also by the presence of more nitrogen atom(s) in the five-membered ring. The conceptual density functional theory (DFT

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• 183-8509, Japan 10.3762/bjoc.18.112 Abstract TiO2 photoelectrochemical and electrochemical radical cation Diels–Alder reactions of arylidene cycloalkanes are described, leading to the construction of spiro ring systems. Although the mechanism remains an open question, arylidene cyclobutanes are found

• previous report by Knowles and Romanov-Michailidis. Conclusion In conclusion, we have demonstrated that radical cation Diels–Alder reactions of arylidene cycloalkanes are enabled under TiO2 photoelectrochemical and electrochemical conditions to construct various spiro ring systems. Although further

• . Formal expression of radical cations. Radical cation Diels–Alder reaction of β-methylstyrene. Radical cation Diels–Alder reaction of β-methylanethole (1). Recovered starting material is reported in parentheses. Radical cation Diels–Alder reactions of the arylidene cycloalkanes (4–7). Recovered starting

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• polycyclic molecules given in Figure 1 are interesting reactive intermediates which could be applied in the Diels−Alder reactions of less reactive or thermally susceptible dienes. Often, these are generated in situ and trapped with dienes in a single pot, such as 7-oxanorbornadiene imides 1–3. For instance

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• the residence times of the reactions outperformed those of the analogous experiments carried out under batch conditions by far [62][63][64]. The heating method was also successfully tested on various thermally conducted pericyclic reactions (Scheme 10, case A), such as in (hetero)-Diels–Alder

• reactions (anthracene (33) and maleic anhydride (34) to the cycloaddition adduct 35 and chromene carbaldehyde 36 and enol ether 37 to the diastereomeric pyrano-chromenes 38), Alder-En reactions (oxomalonate diethyl ester (39) and β-pinene (40) to give the α-pinene derivative 41), and the thermal

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• demethoxycarbonylating annulation of methyl methacrylate (33) with 3-cyanophthalide (32), in the presence of lithium tert-butoxide as catalyst (64% yield) (Scheme 7) [91]. Recently, Dissanayake and co-workers tested the stability of furans to be used as a diene in Diels–Alder reactions for the synthesis of p

• reaction, among pericyclic reactions, is a very important synthetic approach to obtain several molecular scaffolds, including naturally occurring molecules, drugs, polymers, and heterocycles with promising biological activity. Especially, Diels–Alder reactions involving quinones and dienes as starting

• of asymmetric compound 50 catalyzed by a chiral oxazaborolidinium cation (49) [107]. This type of catalyst has been used in several Diels–Alder reactions proving to be an excellent choice for highly enantioselective reactions [108]. For instance, the reaction of menadione (10) with 2

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• based on Diels–Alder reactions of cyclopentadiene with alkynes [13][14][15][16][17][18][19][20][21][22][23]. However, since this synthetic route requires strongly electrophilic alkynes, its scope is limited to products that contain at least one electron-acceptor group, such as an ester, a nitrile or

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• . Review Cycloaddition/addition Cycloaddition reactions have long been applied to molecular container-mediated enzyme-mimicking transformations [27][31][32][33], and the Fujita group has done pioneering research works in this direction [27][34]. In 2006, the authors reported unique Diels–Alder reactions of

• reports of supramolecular host-mediated Diels–Alder reactions of anthracenes, 9,10-adducts bridging the center rings of the anthracene frameworks were generally yielded [35][36][37], which resulted from the high localization of π-electron density at that sites [38]. Besides, these reactions required near

• reactions. Naphthalene is usually hard to undergo Diels–Alder reactions [44][45][46], even though the quantum-mechanical and thermochemical calculations suggest that the reaction is exothermic, which indicates the entropic cost is significant [47]. In 2010, the same group reported another interesting site

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• labeling proteins and visualizing cancer due to the ability of s-tetrazine to fast and biocompatible ligation with alkenes via the inverse electron demand Diels–Alder reactions [29][30][31]. At the same time, azolo-annulated 1,2,4,5-tetrazines remain to be a scarcely studied class of compounds, mainly due

High-speed C–H chlorination of ethylene carbonate using a new photoflow setup

• Takayoshi Kasakado,
• Takahide Fukuyama,
• Tomohiro Nakagawa,
• Shinji Taguchi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16

• [14][15][16][17][18][19][20]. Vinylene carbonate also serves as a useful synthetic building block for Diels–Alder reactions [21][22][23][24][25] and polymerization [26][27][28][29][30]. Results and Discussion Using a PTFE tube and PTFE connectors, we connected the photoflow setup with a chlorine gas