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

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• quick and economically accessible for developing styelsamine B (4) and cystodytin J (1) bioactive derivatives. Synthesis of sebastianine A (38) and its regioisomer (39) The first step of the sebastianine A synthesis was based on a Diels–Alder reaction between a pyrroloquinone used as the dienophile and

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• , which never exceeded 15%, and unreacted 2a were detected in the crude mixture. On the other hand, it is worth noting that although compound 4a can be considered as a good dienophile, its intermolecular Diels–Alder reaction with the triene intermediate formed after the initial CEYM was not observed. This

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• ]. Based on this proposal Shair and co-workers attempted the synthesis of the natural product (−)-longithorone A. Diene 343 and the dienophile 342 were synthesized by several steps and subsequently subjected to the DA sequence to afford the rigid (−)-longithorone A (346, 90%, Scheme 60). Nicolaou and co

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• symmetrical adduct 37 in good yield. Comparable results were observed on adding NPTD (equivalent amount) to pentaene 20 and hexaene 21. Using 36 in excess provided the 2:1-adduct 40 from 21 and led to a complex mixture of adducts from heptaene 22. With tetracyanoethylene (TCNE) as the dienophile, tetraolefin

• is elongated by one double bond: tetraene 19 and dienophile 36 provide cycloadduct 37 in good yield (75%) under mild reaction conditions. Note that only this symmetrical regioisomer is produced – the alternative involving a terminal diene unit is not observed. The spectroscopic data (see Supporting

• compound 41 shown in Scheme 11 is among them; as in all other experiments the terminal double bonds remained untouched. Tetracyanoethylene (TCNE) is usually less reactive as a dienophile than PTAD; this is also the case when the above mentioned oligoenes are employed as the diene components (Scheme 12). As

Glycoluril–tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests

• Yoann Cotelle,
• Marie Hardouin-Lerouge,
• Stéphanie Legoupy,
• Olivier Alévêque,
• Eric Levillain and
• Piétrick Hudhomme

Beilstein J. Org. Chem. 2015, 11, 1023–1036, doi:10.3762/bjoc.11.115

• onto compound 11 [34]. The hydroquinone moieties were subjected to a dehydrogenation reaction using DDQ in THF to reach desired glycolurildiquinone 13 [35] in 91% yield. The Diels–Alder cycloaddition was carried out by treatment of bis-dienophile 13 with TTF derivative 14 [36], able to give rise in

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• . The mixture was heated at 50 °C for 24 h. The solvent was evaporated in vacuo. Subsequent separation on preparative plates coated with silica gel (eluent: CH2Cl2) gave pure products. Method B: The corresponding thioketone (1 mmol) and acetylenic dienophile (2 mmol) were placed in a 4 mL teflon vial

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• first example of [4 + 2] cycloaddition between two diphosphole molecules where 1,2-diphosphole acts as a diene and a dienophile in one reaction. Therefore, these isomeric cycloadducts, 2a–с, can be a source of reactive 1,2-diphospholes containing EWGs 1a–с in the retro-Diels–Alder reaction [19]. Indeed

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• are difficult to synthesize by conventional means, can be conveniently generated in situ at low temperatures. The electrogenerated intermediate is subjected to cycloaddition either by in situ trapping with the dienophile or by using the cation pool approach. Chiba et al. reported an interesting

• dienophile is facilitated. Yoshida, Suga and co-workers reported on the use of electrogenerated N-acyliminium ions as heterodienes in [4 + 2] cycloadditions [66]. It was found that these highly reactive species, generated from silylated carbamate 57 at −78 °C (cation pool method), undergo cycloaddition at 0

• °C with a variety of electron-rich alkenes and alkynes (Scheme 21) to afford 1,3-oxazinan-2-ones 59 and 3,4-dihydro-1,3-oxazin-2-ones 60, respectively. The product yields strongly depend on the electronic character of the substituents on the dienophile. While monoalkyl- and monophenyl-substituted

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• of which are enantioselective [54][55][56]. In Danishefsky’s approach to racemic dysidiolide, the cyclohexene ring of 30 was installed via diastereoselective Diels–Alder reaction of a transient dioxolenium dienophile and chiral vinylcyclohexene 31 [48]. Triene 31 was prepared from α-quaternary ketone

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• (series 1 and 2) from 1-oxo-2-aryl-1H-isoindolium ions (A) and appropriate tert-enamides (Scheme 1). Although this is the first report of the use of tert-enamides as a dienophile for the hetero-Diels–Alder reaction with N-acyliminium cations, formation of isoindoloquinolines (series 1 and 2) was rather

• the dienophile, at least two regioisomers can be visualized for these compounds. Based on our characterization results, only one regioisomer, where the substitution was at position 5 of the isoindoloquinoline ring, was exclusively formed in these reactions. Inverse-electron demand hetero-Diels–Alder

• position. The polarized form of the tert-enamide dienophile, on the other hand, will have a positive and negative charge on carbons α and β to N, respectively. Such polarization can only lead to the regioisomer with the substitution at position 5 of the isoindoloquinoline ring. Even with this

Thermodynamically stable [4 + 2] cycloadducts of lanthanum-encapsulated endohedral metallofullerenes

• Yuta Takano,
• Yuki Nagashima,
• M. Ángeles Herranz,
• Nazario Martín and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2014, 10, 714–721, doi:10.3762/bjoc.10.65

• Discussion Synthesis and characterization of La2@C80 cycloadducts o-Quinodimethanes 2a and 2b were generated in situ by thermolysis of the corresponding sultines 1a and 1b in toluene at 80 °C (Scheme 1). The highly reactive intermediates are trapped efficiently by La2@C80, which acts as a dienophile to form

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• maleimide derivatives. Our preference for this dienophile was dictated by a recent patent on the lifespan altering properties of cycloadducts involving maleimide dienophiles [20]. Moreover, very recently we have characterized some furo[3,2-h]quinoliniums as potent non-detergent spermicides [19], which

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• solvent [31]. The use of a stoichiometric amount of EtAlCl2 as Lewis acid catalyst allowed a lowering of the reaction temperature, a shortening of the reaction time and good stereocontrol (Scheme 2) [32]. Alternatively, the simple heating of a mixture of a 1-bora-1,3-diene, a dienophile and an aldehyde

• dienophile used (Scheme 5) [39]. Finally, interesting results were reported with methyl acrylate and dienes derived from tartrate esters (9/1 de, 70% ee for the major isomer) (Scheme 6) [40]. In 2003, Hall and co-workers reported the application of electron-rich dienylboronates in one-pot tandem Diels–Alder

• -coupled using palladium catalysis. A one-pot sequence was also developed, first heating the boron diene with the dienophile, then adding an aryl halide, Pd(OAc)2 (5 mol %), K2CO3 (3 equiv) and finally refluxing the mixture in EtOH or MeOH for 5 h (Scheme 13). Reactions with various aryl halides

One-pot cross-enyne metathesis (CEYM)–Diels–Alder reaction of gem-difluoropropargylic alkynes

• Santos Fustero,
• Paula Bello,
• Javier Miró,
• María Sánchez-Roselló,
• Günter Haufe and
• Carlos del Pozo

Beilstein J. Org. Chem. 2013, 9, 2688–2695, doi:10.3762/bjoc.9.305

• generation Hoveyda–Grubbs catalyst I was heated under ethylene atmosphere (1 atm) for 2 h, the clean formation of diene 2a was observed. This newly formed diene was isolated in 70% yield and it reacted smoothly with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione as dienophile at room temperature to afford, after

• chromatographic purification, the corresponding Diels–Alder adduct 3a in 60% yield (Scheme 2). It was interesting to find that this sequence can be performed as a one-pot procedure. Thus, when the formation of the diene intermediate 2a was completed (determined by TLC), the dienophile was added to the reaction

• diethyl acetylenedicarboxylate (DEAD) afforded adduct 3c in 51% yield, and no aromatization was observed during the process (Table 1, method A, entry 3). When maleic anhydride was used as dienophile, the corresponding diacid 3f, arising from the anhydride ring opening under the reaction conditions, was

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• selenide. Oxidation and elimination of the corresponding selenoxide at elevated temperature generated the necessary dienophile, which directly underwent an intramolecular endo-Diels–Alder reaction to give the isoindolinone 68. For the synthesis of 69 another ten steps were necessary to discriminate between

• muironolide A (204) shares this potential. A first attempt to access 204 in the laboratory was reported by Molinski shortly after the isolation (Scheme 26) [151]. Coupling of the dienophile precursor 198 with sorbic acid (199) gave a tertiary amide, which was converted to 200 via a reduction–oxidation

Integrating reaction and analysis: investigation of higher-order reactions by cryogenic trapping

• Skrollan Stockinger and
• Oliver Trapp

Beilstein J. Org. Chem. 2013, 9, 1837–1842, doi:10.3762/bjoc.9.214

• adequate range for GC measurements. Besides, the Diels–Alder reaction is a commonly used reaction and of broad interest. The used dienophile, benzyne, is highly reactive and must be generated in situ [21][22][23][24]. This can be achieved by chemical decomposition initiated by fluoride [25], lithium [22