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

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• hindered naphthoquinone monoketal dienophile 3 with diene 4. The use of thiourea catalysis allowed for the first time the highly selective synthesis of the exo-product 2a in up to 63% yield. In this reaction a new quaternary center was built. The so formed cycloaddition product 2a represents the ABC

• ][8]. In our recent studies towards a synthetic access to the natural product beticolin 0 (1) [9] (Scheme 1), we have found that naphthoquinone monoketals are suitable building blocks for our designed synthesis [9]. In our retrosynthetic approach, the naphthoquinone monoketal dienophile 3 was found to

• undergo cycloaddition with diene 4 to tricycle 2, which represents the ABC-ring system of beticolin 0 (1) and other beticolins [10]. We found that dienophile 3 and diene 4 can undergo a cycloaddition by applying either thermal conditions or microwave irradiation to these both compounds (Table 1) [9

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• nitroalkenes 5a–c as heterodienes, ethyl vinyl ether (EVE) as a dienophile, and selected electron-deficient alkenes as 1,3-dipolarophiles. The employment of different organic solutions of LiClO4 or LiCl as promoter systems provided the respective nitroso acetals with yields from 34–72% and good levels of

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• dimerization through a DA reaction [13]. The first DA reaction involving the –C=C–C=P– moiety of phosphinine as a diene was reported by Märkl and Lieb [14], while Mathey and Alcaraz showed that phosphinine could react as a dienophile as well, with the reaction taking place at the >C=P– functionality of

• catalyst In the DA reactions catalysed by excess dialkylaluminium chloride, formation of the chelate complex cation 11 of the dienophile (Scheme 3) has been established experimentally [36][37][38], and the high reactivity of the dienophile in the presence of the organoaluminium catalyst was attributed to

• -phosphaindolizine-η1-P-aluminium(O-menthoxy) dichloride with 2,3-dimethylbutadiene. Formation of the cationic 1:1 complex of the dienophile and dialkylaluminium. Disproportionation of the 1:1 complex of 2-phosphaindolizine and Al(O-menthoxy)Cl2. Attack of 1,3-butadiene on Si and Re faces of >C=P– functionality of 2

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• there are two α-hydrogen atoms in the adduct aromatization can be accomplished by base treatment (e.g. formation of 153 and 156). Incorporation of substituents into the double bond of the dienophile slows down the addition process or prevents it completely. Unusual dienophiles such as cyclobutadiene or

• ] cycloaddition mode compete [123]. Occasionally highly alkylated bisallenes such as 24 also provide ene-addition products. If the double-bond dienophile is replaced by an activated triple-bond dienophile 173, another course of events is observed (Scheme 42) [21][124][125][126]. In this case the Diels–Alder step

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• ]. However, a survey of literature reveals that a Povarov reaction with in situ generated β-enamino ester as dienophile has not been reported until now. Recently, Zhu and Masson successfully developed three-component Povarov reactions using enamides as dienophiles leading to a highly efficient synthesis of

• of N-aryl aldimine B as the N-hetero diene with β-enamino ester A as the dienophile may give directly the tetrahydroquinoline 1. At present it is very difficult to distinguish these two reaction paths. It may be due to the fact that the four sequential reactions are all retro equilibrium reactions

• propiolates, and successfully established the imino Diels–Alder reaction with β-enamino ester as dienophile. This reaction provides a convenient and stereoselective procedure for the preparation of 2-aryl-4-arylamino-1,2,3,4-tetrahydroquinoline-3-carboxylates in satisfactory yields. Furthermore, we

Imidazolinium and amidinium salts as Lewis acid organocatalysts

• Oksana Sereda,
• Nicole Clemens,
• Tatjana Heckel and
• René Wilhelm

Beilstein J. Org. Chem. 2012, 8, 1798–1803, doi:10.3762/bjoc.8.205

• [10][16][17]. Taking the soft Lewis acidic character of imidazolinium salts into consideration, we were interested to apply these salts in a Diels–Alder reaction with ethyl crotonthioate as dienophile. Due to the low electronegativity of sulfur it would be difficult to catalyze this reaction with

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• MacMillan on various model systems (Figure 3) [37]. The effect of these catalysts is based on the formation of iminium ions by condensation of the dienophile bearing a carbonyl group, with the sterically hindered imidazole catalyst. In this way, one side is shielded and only the other side can be attacked

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• because it mimics a furanose but without an optically active center, making the synthesis of defined molecules much easier than on a furanose core. Synthetically it is easily accessible and is a dienophile, which allows attachment of marker molecules in a Diels–Alder reaction, leaving the hydroxy groups

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• glycine in toluene gave the desired tricyclic product 19 as a single stereoisomer. NOESY studies verified the stereochemistry as shown. Only one of the two alkene groups acts as the dienophile, as expected for conformational reasons. This synthesis (six steps from nitrile 3) represents an efficient entry