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

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• Diels–Alder reaction selectivity [28]. The DAR of cyclopentadiene with p-benzoquinone is a well-known example of cycloadditions, and some results can be found on the control of the selectivity to the different isomers. In homogeneous phase, equimolar amounts of diene and dienophile afford two isomers

• acid sites in the solids We have prepared Ti-Beta [31], Sn-Beta [32] and Al-Beta (Si/Al = 50) [33] considering that Lewis acid catalyzes the DAR [1]. This effect is known to occur by complexation of the carbonyl group of the dienophile with the Lewis acid that increases the electron deficiency of the

• dienophile, reducing the energy gap. The results presented in Figure 2a, b clearly show an important increase in activity due to the presence of Brønsted and, especially, of Lewis acid sites. Indeed, despite the fact that the crystallite size of Ti- and Sn-Beta zeolites is much larger than Al-Beta (Table 1

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• standard Ugi–Smiles adducts 3 (Table 3). The lack of oxatricyclic epoxyisoindoline formation is not surprising, given the more remote relative proximity of the diene and dienophile. Propargylamine and 3-butenylamine were also satisfying partners with 3-furaldehyde in this process. Ugi–Smiles reactions with

• observed for 2- and 3-furaldehyde with a variety of amine components. In the presence of a competent dienophile, the Ugi–Smiles coupling is followed by a facile intramolecular Diels–Alder cycloaddition to generate oxatricyclic N-arylepoxyisoindolines. Initial results with thiophene-2-carboxaldehyde show

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• , Czech Republic Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA 10.3762/bjoc.12.184 Abstract The hetero-Diels–Alder reaction between a nitroso dienophile and a conjugated diene to give the 3,6-dihydro-2H-1,2-oxazine scaffold is useful for the synthesis of

• biologically active compounds. It is a variant of the Diels–Alder reaction where either the diene or the dienophile contains a heteroatom. Hetero-Diels–Alder reactions between conjugated dienes and nitroso dienophiles affording 1,2-oxazines are utilized for the synthesis of many biologically active molecules

• –Alder reactions using alkyl- or arylnitroso dienophiles were reported by Wichterle [11] and Arbuzov [12][13] in 1947 and 1948, respectively. Among the early reported reactions using an acylnitroso compound as the dienophile, an interesting study by Kirby and Sweeny in 1973 [14] reported that the

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• dienophile [6][7][8]. Cage compounds with interesting applications have been assembled by a cyclization reaction starting with suitably functionalized norbornene derivatives [9][10][11]. Moreover, the norbornene unit induces a hairpin-like architecture when it is incorporated into a peptide chain. This

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• fixed the conformation of the dienophile (Figure 1) [16]. Given this precedent, we aimed to gain further insight into this type of interaction, by exploring the effect caused by the introduction of electronically different substituents at the aromatic ring of the chiral auxiliary. For this reason, we

• auxiliary. Results and Discussion The synthesis of acrylate derivatives 6a,b bearing CF3 and OMe substituents in the para position of the phenoxy group is depicted in Scheme 1. Levoglucosenone (1) was used as a dienophile to react with the corresponding 9-substituted anthracenes 2a,b, which are easily

• S/R ratios are considerable high in the absence of Lewis acids. The high inductive capacity is interpreted in terms of the fact that the conformation of the dienophile is fixed by a π-stacking interaction. The reactions promoted by Et2AlCl produced the reversed endo S/R diastereoselectivity with a

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• dienophile component in inverse-electron demand Diels–Alder reactions, a series of new dihydroindeno[1,2-c]pyran derivatives was synthesized. Thus, the addition of freshly distilled indene as a diene component to oxadiazinones 1 as the dienophiles [29] under acidic conditions (TFA, TFAA) led to the formation

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• , the asymmetric Diels–Alder (D–A) reaction between the N-sulfonamide-3-hydroxy-2-pyridone-based dienes 52 and different dienophile substrates was developed using the bifunctional cis-2-trialkylaminoindanol organocatalyst ent-41 [56]. We show herein the reactivity of this family of dienes with several

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• 8-oxabicyclo[3.2.1]octane 21 framework. In this reaction, the main factor of achieving high yields or enantioselectivities, is how electron-rich or electron-poor, the dienophile is. Electron-rich olefins, like the benzyl vinyl ether and ethyl vinyl ether, reacted with success providing high yields

• dienophile 32, using compound 34 as the catalyst (Scheme 12) [23]. This reaction provided products in 84–99% yield and with a diastereoselectivity of up to >20:1 and excellent enantioselectivity (88–99% ee). In 2015, Dixon, Paton and co-workers demonstrated an elegant route to morphan skeletons, utilizing

• tertiary amine-thiourea 56 was reported by Bernardi, Ricci and co-workers for the Diels–Alder reaction of 3-vinylindoles 51 (Scheme 18) [29]. The authors utilized either maleimides 52 or quinones 53 as the dienophile, affording the products 54 and 55 in excellent yields and enantioselectivities, after

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• -3-carboxylic acid derivatives 3, constrained analogues of tryptophan, could be synthesized by Diels–Alder reactions between 2-vinylindoles 1 [22] as dienes and methyl 2-acetamidoacrylate (dehydroalanine) 2 [23] as dienophile (Scheme 1). Reported [4 + 2] cycloaddition reactions of methyl 2

• -carbon terminus of the diene and the double bond of the dienophile occurs almost simultaneously allowing for the preservation of the stereochemistry around the outer-ring diene double bond. Besides, in the presence of a terminal p-tolyl group on the diene moiety (see Table 2, entries 1 and 2) the

• reactivity upon specific substitution patterns at the indole nucleus were observed by us in competitive Diels–Alder cycloaddition/Michael addition reactions of vinylindoles with classical dienophile and in competitive cycloaddition/hydroarylation reactions with allenes, see [20][21] for a more detailed