Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• 3-(indol-3-yl)-1,3-diphenylpropan-1-one gave the expected indole-substituted chalcone A, which comprises the desired 3-vinylindole scaffold as the reactive diene. In the meantime, the carbonyl group of the chalcone is protonated to give the activated dienophile in the presence of p-toluenesulfonic

• acid. Secondly, the Diels–Alder reaction of indole-chalcone A with the dienophile results in the tetrahydrocarbazole B having an exocyclic C=C bond. Thirdly, a new tetrahydrocarbazole intermediate C is formed by a 1,3-H shifting process. The resulting tetrahydrocarbazole intermediate (C) might be a

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• the tetrazine ring is an electron-poor diene, the dibenzosuberenone (1) dienophile is not electron-rich enough. Therefore, for such cycloaddition reactions, the tetrazine must be substituted by EWGs to decrease the electron density of the diene. Consequently, our results confirm that EDGs and EWGs

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• powerful tool for assembling a variety of fluorinated carbo- and heterocycles using either the diene [24][25][26][27][28][29][30] or the dienophile component [31][32][33][34][35][36][37][38][39] as fluorine-containing building blocks. The application of [4 + 2] cycloadditions for the preparation of

• majority of the substituents on the aryl group of the nitrostyrenes 1. However, a higher diastereoselectivity towards the endo-isomer was observed when strong electron-withdrawing groups (EWGs) were present in the dienophile. For example, in the case of the 4-cyano and the 3-nitro-substituted derivative

• , the ratio of endo/exo was 2:1. The stereochemistry of the products 2a–l can be unambiguously assigned using 1H NMR spectroscopy. According to the literature data [59] the dienophile-derived proton at C6 resonates at lower field in the exo-form than the corresponding proton of the endo-isomer. For

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based

• solvent dependence of the stereochemical induction of the Diels–Alder reaction by the phenylethyl-derived ligand 2 was studied using N-benzylmaleimide (8e) as dienophile (Table 1). The solvents dioxane (17% ee) and acetone (14% ee) showed a slight decrease of the enantioselectivity compared to THF (21% ee

• compared to Li[Li3(5)6Ti2] [35][36]. Thus, the higher amount of undesired monomer in solution of Li[Li3(1)3(6)3Ti2] resulted in a partial switch-off of the stereoselectivity. Screening of the dienophile The variation of the dienophile was studied in chloroform using the helicate Li4[(1)3(4)3Ti2]. N

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• method toward the preparation of 3-arylated-4-nitrophenols. On the other hand, nitroalkenes possess an electron-deficient double bond, and hence, they serve as an excellent Michael acceptor and dienophile [12][13][14][15][16][17][18][19]. When β-nitrostyrene (1, Ar = Ph) is subjected to the Diels–Alder

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• intermediates 13, results in hydroxyisoindolines 11, which can finally tautomerize to aldehydes 2a,b. In the previous report, we have demonstrated the existence of an equilibrium in the course of the transformation of 1a to 2a by trapping isoindole intermediate 4a with N-phenylmaleimide as a dienophile in the

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• reactivity of 2-vinylpyrroles substituted by electron-withdrawing groups [34][35]. Interestingly, all the 2-vinylpyrroles, including the N-unsubstituted 16a,b or the N-substituted ones 8a and 8c–j, furnished a high endo stereoselectivity with dienophile 7c, except the N-substituted 2-acrylonitrile pyrrole 8b

• nitrogen atom of the heterocycle. Since it is not clear what factors favor this relevant selectivity, the geometry and energy of the TSs were calculated for some of the diene–dienophile pairs depicted in Table 2 (vide infra). Cyclization via an intramolecular Heck arylation reaction Before attempting the

• (Supporting Information File 1, Table S1). Hence, the latter dienes should be more reactive than diene 8b, and consequently more stereoselective [54][55][56]. In contrast, the Gibbs energy for the diene/dienophile 8c/7b (88.8:11.2) did not completely match the experimental endo/exo (99:1) ratio, but the ZPE

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• reaction proved efficient when adding the dienophile and heating in the same pot just after the RCEYM (Scheme 3). From mestranol derivative 5a, endo cycloadducts 16a–e were obtained in good to excellent yields. However, the reaction with maleic anhydride (12) gave a poor yield attributed to the reactivity

• imposed by the steroid skeleton on the dienyl tetrahydrofuran α-face, imposing orbital interactions with the dienophile from the β-face (Figure 3b). All these structures have an extended skeleton, with the steroid part being perpendicular to the cycloadduct moiety thanks to the spiro junction. Conclusion

• irradiation. The microwave tube was opened and the dienophile (1.2 mmol) was added in one portion. The mixture was stirred at 150 °C for 35 min. The solvent was removed and the crude material was purified by chromatography on silica gel (petroleum ether/EtOAc 8:3) to afford the product. Structure of four 17

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ) (Scheme 3) [17][18][19][20][21]. To produce Ambrelux (32), myrcene (1) is reacted with dienophile (31) in a Diels–Alder cycloaddition promoted under Lewis-acidic conditions. In order to obtain Iso E Super® (33), Brønstedt acid-mediated cyclisation, similar to the one utilised for the first synthesis of

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• reported as intermolecular cycloaddition reactions, there are some interesting reports regarding the intramolecular cycloaddition of fulvenes, summarised in Table 1. For the intramolecular cycloadditions of pentafulvenes, the fulvene has been reported to react as both diene and dienophile depending on the

• length of the extended pentafulvene chain, and the role of the fulvene in the reaction (diene or dienophile) [127]. In these examples, kigelinol and neoamphilectane are of great interest in biomimetic and natural product chemistry, as they exhibit antitrypanosomal [128][129] and antimalarial [130

• , when the fulvene has an EWG attached, it is more likely to function as a dienophile in an inverse electron-demand Diels–Alder (iEDDA) reaction [153][154][156]. This requires the other reactant to have strong EDGs in order to function as a diene, otherwise fulvene dimerization becomes the preferred

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• : asymmetric organocatalysis; axial chirality; biaryls; hydrogen bond; oxo-Diels–Alder reaction; Introduction The Diels–Alder (DA) reaction is a useful and easy-to-perform method for the synthesis of six-membered rings through the direct formation of C–C bonds between a diene and a dienophile (a substituted

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• -substituted tetrazines via a Diels–Alder reaction with inverse electron demand has been studied with NMR and with electrospray ionization mass spectrometry. A catalytic cycle with three intermediates has been proposed. An enamine derived from L-proline and acetone acts as an electron-rich dienophile in a [4

• formation of the enamine I seems plausible. It is an electron-rich dienophile which could undergo a [4 + 2] cycloaddition with the electron-poor aryl-substituted tetrazine 2 in a Diels–Alder reaction with inverse electron demand. The bicyclic Diels–Alder intermediate II then might undergo a retro-Diels

• from the enamine/dienophile I and the tetrazine. Thus, we decided to use NMR (nuclear magnetic resonance) spectroscopy and ESI mass spectrometry in combination with a charge-tagging strategy to get deeper insights in the presence or absence of the three intermediates by experimental means. Results and

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• functional group and the substrate structure and may follow a different reaction course than what is usually observed. In cases where ROM–RCEYM occurred, the resulting 1,3-diene reacts in situ with the dienophile to provide condensed tetracyclic systems. Keywords: Diels–Alder reaction; domino process; enyne

• derivative 2 would provide the tricyclic 1,3-diene 3 which on Diels–Alder reaction with a dienophile would enable access to condensed polycyclic structures 4 (Scheme 2). Thus an appropriately chosen norbornene derivative and a dienophile may provide the B/C/D/E ring system of retigeranic acids. Herein we

• compound 12b was established through analysis of its NMR spectra. Isolation of 12b dictated that metathesis of 7b proceeded through the formation of the triene 9b. Stereochemical assignment to the adduct follows from addition of the dienophile from the least hindered face (opposite to CH2OTBS group) of the

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• attacks the more electrophilic C-atom, we postulate that compounds 4i–l and not their isomers 5a–d are formed in these reactions. This assumption is supported by the intramolecular H-bonding, which enhances the electrophilicity of C(3) in the dienophile 2d. Finally, the structure of 4k was established by

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• complete electron delocalization, whereas the carbonium ion 200 (and 201) formed from 190 indicated considerably less electron delocalization (Scheme 34). 3.2.3. Cycloaddition reactions: 2,3-Benzotropone (12) possesses a high functional tolerance towards both the diene and dienophile and undergoes the

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• one of the most powerful methods to construct six-membered ring systems. A “normal” Diels–Alder reaction must consider an electronic matching of the substrates, with an electron-rich diene and electron-deficient dienophile as the general combination. Although having both an electron-rich diene and

• dienophile is a less- or non-effective combination, oxidative SET has proven to be able to overcome this mismatch and such a strategy is well-known as a radical cation Diels–Alder reaction. The use of trans-anethole as a model electron-rich dienophile is the representative example in this class. It was first

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• the IEDDA reaction. However, the yields were significantly lower in reactions catalyzed with B when compared to catalyst A (Table 1, entries 1–4). Nonetheless, when a more active dienophile 6-ethoxy-1-methyl-1,2,3,4-tetrahydropyridine (4f) was subjected to the IEDDA reaction of phthalazine (3), the

• phthalazine: In a Schlenk tube charged with a stirring bar, the air-stable bidentate Lewis acid catalyst B (5.00 mol %) and the stated solvent were added under N2. Then, the phthalazine (1.00 equiv), dienophile (2.00 equiv; for enamines, generated in situ from aldehyde and amine) were added subsequently. The

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• Mannich reactions where the process involves an ortho-quinone methide (o-QM) intermediate. The reactions are classified on the basis of the o-QM source followed by the reactant, e.g., the dienophile partner in cycloaddition reactions (C=C or C=N dienophiles) or by the formation of multicomponent Mannich

• adducts. Due to the important pharmacological activities of these reactive o-QM intermediates, special attention is paid to the biological activity of these compounds. Keywords: aminophenols; [4 + 2] cycloaddition; dienophile; Mannich reaction; ortho-quinone methide; Review Introduction The Mannich

• intermediate reacts with the nucleophile (dienophile) species in different reactions to form a wide range of heterocyclic compounds. Reactions with C=C dienophiles Reactions of o-QMs with different C=C dienophiles are listed in Table 3. Osyanin et al. reported the efficient reaction of quaternary ammonium salt

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• reacted with both dienophiles in a stereospecific manner, and in both cases mixtures of two stereoisomeric cyclohexenes with preserved stereochemistry in the dienophile fragment were obtained [45]. On the other hand, reactions with 1,1-dimethoxybuta-1,3-diene (42) led, in both cases, to similar mixtures

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• -12); MS (EI+) m/z: 166 [M+.] (1), 110 [C7H10O]+ (93), 97 [C6H9O]+ (100), 79 [C6H7]+ (19), 69 [C5H9]+ (26), 67 (16), 55 (19). Diels–Alder reactions General procedure: Dimer 2-TT (1.5 equiv) and the corresponding dienophile (1 equiv) were dissolved in toluene (0.5 M) and stirred for 4 hours at 150 °C

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• the D-series thiopeptides have been explored, (i) the late-stage construction of the pyridine core through [4 + 2] cycloaddition reaction flanked with the main difficulties to prepare the dienophile and alkene bearing the adequate thiazolyl moieties or (ii) the direct connection and construction of

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• biscembranoids are believed to originate as products from Diels–Alder cycloaddition between two cembranoid units. Besides methyl sarcoate, only methyl tetrahydrosarcoate and isosarcophytonolide D are reported to act as dienophile (western part) in over 60 described biscembranoids [49]. The western parts in the

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• fragrances are based on myrcene, such as geraniol, nerol, linalool, menthol, citral, citronellol or citronellal [3]. The terminal diene moiety present in myrcene allows for a reaction with a suitable dienophile following the Diels–Alder reaction mechanism. Dahill et al. describe the synthesis of the Diels

• results for the continuous-flow reaction of myrcene (1) with acrylic acid (2b) in a tubular flow reactor (reactor volume: 20 mL) and a plate flow reactor (reactor volume: 105 mL); all entries were reacted with a myrcene to dienophile ratio, R, of 0.9, and cMYR,0 of 2.8 mol/L. Supporting Information

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• employing MLA as dienophile was described [3][4][5][6]. In a recent NMR study we demonstrated that, poly(MLA) prepared via free radical polymerization contains mainly isotactic units. Furthermore, we found that the polymer attached lactide rings react like activated esters and thus readily undergo