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 and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• two different research groups [30][31][32][33] and additionally a number of different synthetic routes [34][35][36][37][38] to the spiroketal core structure have been published, including a hetero Diels–Alder reaction [39], a palladium(0)-catalyzed coupling [40][41][42][43][44][45] and a condensation

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• product ilicicolin H (9) (Figure 3) [20][21] along with fischerin, apiosporamide and YM-215343, displays a 3-decalinoyl-4-hydroxypyridin-2-one skeleton wherein the decalin unit may arise biosynthetically from a Diels–Alder reaction within the polyketide-derived side chain [1][22]. As a further

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

• Boubacar Sow,
• Gabriel Bellavance,
• Francis Barabé and
• Louis Barriault

Beilstein J. Org. Chem. 2011, 7, 1007–1013, doi:10.3762/bjoc.7.114

• represents a significant synthetic challenge. This type of architectural feature is embedded in various complex biologically active compounds such as hyperforin and garsubellin A. Herein, we report a highly diastereoselective one-pot Diels–Alder reaction/Au(I)-catalyzed carbocyclization to generate bicyclo

• Diels–Alder reaction/Au(I)-catalyzed 6-endo-dig carbocyclization (Scheme 3). Cycloaddition between diene 12 and dienophile 13 should provide the endo cycloadduct 14, which, in the presence of a gold(I) catalyst, would form the gold complex A. This undergoes a carbocyclization of enol ether [24][25][26

• ) are underway and will be reported in due course. Structures of naturally occurring PPAPs. Gold(I)-catalyzed 6-endo-dig cyclization. Synthesis of papuaforin A core 4. Proposed domino Diels–Alder reaction/gold(I)-catalyzed cyclization. One-pot Diels–Alder cycloaddition/gold(I) catalyzed carbocyclization

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• multi-component tandem reaction that involved novel direct alkyne 279–amine 280–glyoxylic acid (278) coupling, intramolecular cyclization of α-N-substituted β-alkynoic acid, and subsequent reaction (Scheme 49) [147]. An intermolecular hetero-dehydro-Diels–Alder reaction between captodative 1,3-dien-5

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• + 2] cycloaddition (Diels–Alder reaction) is only very rarely observed photochemically (vide infra). Photocycloadditions are not limited to simple alkenes, and even the thermally very stable benzene core has been shown to become quite reactive upon excitation with photons. It can be converted into

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• is multiplicity-dependent: The direct irradiation of 1a leads to the dibenzocyclooctatetraene 3a in a singlet reaction that occurs via an initial [2 + 2] cycloaddition followed by a [4 + 2] retro-Diels–Alder reaction [27][28][29][30]. In the presence of a triplet sensitizer, e.g., acetone or

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• homopentaprismane, somewhat analogous to the original cubane synthesis. As shown in Scheme 7, Diels–Alder reaction of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene with p-benzoquinone gave 37 which underwent photolytic [2 + 2] closure to the pentacyclic dione 38. Subsequent dechlorination and functional group

Ene–yne cross-metathesis with ruthenium carbene catalysts

• Cédric Fischmeister and
• Christian Bruneau

Beilstein J. Org. Chem. 2011, 7, 156–166, doi:10.3762/bjoc.7.22

• synthesis of Anolignans [48] and another closely related example is shown in the preparation of Amphidinolide E [50][51] where the diene system is extended by further cross-metathesis with 2-methylpenta-1,4-diene (Figure 2). The Diels–Alder reaction is one of the most popular transformations of 1,3-dienes

Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes

• Yannick Borguet,
• Xavier Sauvage,
• Guillermo Zaragoza,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133

• cyclopentadiene and trichloroacetic acid was already observed by Quayle et al. under similar conditions [13][14]. These authors successfully trapped the diene via a Diels–Alder reaction with maleic anhydride. They also reported that a heterobimetallic catalytic system derived from the Grubbs second-generation

Synthesis of oxa-bridged derivatives from Diels–Alder bis-adducts of butadiene and 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene

• Faiz Ahmed Khan and
• Karuppasamy Parasuraman

Beilstein J. Org. Chem. 2010, 6, No. 64, doi:10.3762/bjoc.6.64

• . We were interested in exploring the previously overlooked stereochemical outcome of the Diels–Alder reaction between 1a and 1,3-butadiene [15][16]. The bis-adduct obtained from 1a and gaseous 1,3-butadiene was previously assigned as “endo, exo-bis(7,7-dimethoxy-1,2,3,4-tetrachloronorborn-2-en-5-yl

• see if any bromo derivative, corresponding to the diastereomer 6 in the chloro series, would furnish crystals suitable for X-ray analysis. The Diels–Alder reaction between 1,2,3,4-tetrabromo-5,5-dimethoxycyclopentadiene 1b and 3-sulfolene under the same experimental conditions as described for the

• . Conclusion In conclusion, we have demonstrated that the Diels–Alder reaction between 1 (diene component) and 1,3-butadiene (bis-dienophile component) proceeds via endo-endo addition mode to give a 1:1 mixture of diastereomeric bis-adducts. The diastereomeric bis-adducts were separated and transformed into

One-pot three-component synthesis of quinoxaline and phenazine ring systems using Fischer carbene complexes

• Priyabrata Roy and
• Binay Krishna Ghorai

Beilstein J. Org. Chem. 2010, 6, No. 52, doi:10.3762/bjoc.6.52

• carbonyl derivatives 1A/1B with simple γ,δ-unsaturated Fischer carbene complex 10 was investigated. This reaction proceeds via a tandem process involving the formation of azaisobenzofuran 11, followed by intramolecular Diels–Alder reaction, and ring opening of 12 to afford azahydrophenanthrone derivatives

• trapped through Diels–Alder reaction with dienophiles leading to the synthesis of nitrogen containing heterocyclic analogues of quinoxaline and phenazine, respectively, in one-pot. This is the first report of in situ generation of furo[3,4-b]pyrazine intermediates. Synthetic plan towards quinoxaline

Synthesis of fluorinated δ-lactams via cycloisomerization of gem-difluoropropargyl amides

• Satoru Arimitsu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2010, 6, No. 48, doi:10.3762/bjoc.6.48

• difluorodihydropyridinones via a ring-closing metathesis reaction, and of 4,4-difluoro-3-oxoisoquinolines through a ring-closing metathesis–enyne metathesis tandem reaction. These products, in turn, undergo a Diels–Alder reaction to yield heterotricyclic systems in moderate to good yields. Keywords: bicyclic lactams

• diverse suite of δ-lactams because enynes are suitable partners in ring-closing metathesis reactions or cycloisomerizations. An additional benefit of using enynes in metathesis reactions is that the resulting diene product could be further elaborated using a Diels–Alder reaction to construct bi- or

• by a tandem metathesis reaction, this would permit the synthesis of multi-substituted gem-difluoroisoquinolinones through a subsequent Diels–Alder reaction (eq 2, Scheme 2) [28]. In this regard, we screened various ruthenium carbene complexes using 1,7-enyne amide 1a and styrene 8a as a model

Preparation, structures and preliminary host–guest studies of fluorinated syn-bis-quinoxaline molecular tweezers

• Markus Etzkorn,
• Jacob C. Timmerman,
• Matthew D. Brooker,
• Xin Yu and
• Michael Gerken

Beilstein J. Org. Chem. 2010, 6, No. 39, doi:10.3762/bjoc.6.39

• association with electron-rich guest compounds. Results and Discussion Synthesis of fluorinated bis-quinoxalines The general route [19] to bis-quinoxaline targets (Scheme 2) utilizes a twofold Diels–Alder reaction of a cycloalkadiene (5,6) with cyclopentadienone derivatives (7), subsequent oxidation of the

• modifications in the pincer sidewalls (degree of fluorination). Although only the larger cyclooctadiene-derived scaffolds 16a–d could function as molecular tweezers, we also synthesized the fluorinated cyclohexadiene-derived compounds 15b–d with their smaller π-π–distances. A Diels–Alder reaction of

• twofold Diels–Alder reaction of diene 6 and led to a mixture of the syn- and anti-bis-adducts in a 1:4 ratio [26][27]. Since the separation of the crucial syn-isomer 9a from anti-compound 9a′ by repeated recrystallization did not furnish the pure endo,endo,syn-isomer 9a in our hands, we focused on the new

Novel loop-like aromatic compounds: a further step on the road to nanobelts and nanotubes

• Venkataramana Rajuri,
• Dariush Ajami,
• Gaston R. Schaller,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2010, 6, No. 30, doi:10.3762/bjoc.6.30

• characterization of new compounds 2–6 were accomplished. As a common synthetic methodology, the Diels–Alder reaction was applied to 9,9′,10,10′-tetradehydrodianthracene (TDDA) (7) to furnish the [12]annulenes 2 and 3 [16]annulene 6 and adduct 5. Keywords: [n]annulenes; Diels–Alder reaction; nanobelts

• analysis. The pure hydrocarbons 2 and 3 were prepared by Diels–Alder reaction of either 7 or 1 [20] with 1,2-bis(dibromomethyl)benzene (8) and sodium iodide to furnish the desired compounds, 2 and 3, in 60 and 40% yield, respectively (Scheme 1 and Scheme 2). During this simple one pot reaction, the sodium

• iodide induces a 1,4-elimination reaction of 8 resulting in the formation of the highly reactive quinodimethane 5,6-bis(bromomethylene)cyclohexa-1,3-diene (9). Diene 9 and the central olefinic double bond of 1 react in a Diels–Alder reaction, followed by a double dehydrobromination, to afford the desired

Synthesis of some novel annulated pyrido[2,3-d]pyrimidines via stereoselective intramolecular hetero Diels–Alder reactions of 1-oxa-1,3-butadienes

• Mohit L. Deb and
• Pulak J. Bhuyan

Beilstein J. Org. Chem. 2010, 6, No. 11, doi:10.3762/bjoc.6.11

• Diels–Alder reactions involving 1-oxa-1,3-butadienes. Keywords: β-halo aldehydes; hetero Diels–Alder reaction; 1-oxa-1,3-butadiene; pyrido[2,3-d]pyrimidines; uracil; Introduction The importance of uracil and its annulated derivatives is well recognized by synthetic as well as biological chemists [1][2

• . This powerful reaction method does not only allow the efficient synthesis of complex compounds starting from simple substrates but also permits the preparation of highly diversified molecules. One such reaction type, the oxabutadiene Diels–Alder reaction is a very useful method for the synthesis of

• base catalyst (usually piperidine) to produce the 1-oxa-1,3-butadienes 5 which underwent intramolecular Diels–Alder reaction under reflux conditions in toluene (12 to 15 h) to give the cycloadducts. In most of cases the formation of two compounds was observed. The compounds were separated by column

Solvent-free phase-vanishing reactions with PTFE (Teflon^®) as a phase screen

• Kevin Pels and
• Veljko Dragojlovic

Beilstein J. Org. Chem. 2009, 5, No. 75, doi:10.3762/bjoc.5.75

• ]. One of the reasons for a low yield is that Diels-Alder reaction of cyclopentadiene and acrylic acid gives a large amount of the exo isomer, which cannot cyclize. The same reaction with dimethyl fumarate (27) in place of acrylic acid gave the corresponding iodolactone 28 in 87% yield. Cyclopentadiene

Preparation and Diels–Alder/cross coupling reactions of a 2-diethanolaminoboron- substituted 1,3-diene

• Liqiong Wang,
• Cynthia S. Day,
• Marcus W. Wright and
• Mark E. Welker

Beilstein J. Org. Chem. 2009, 5, No. 45, doi:10.3762/bjoc.5.45

• this Diels–Alder reaction via NMR spectroscopy but when we try to perform this reaction under pseudo first order conditions at −10 °C, we can only say that the t1/2 is less than 4 minutes. Attempts to get more accurate kinetic data by NMR at −40 °C resulted instead in diene 2 precipitation. This diene

• analysis indicates a build-up of electron density on carbons C1 and C4 of 0.15e and 0.14e respectively in 2-diethanolaminoboronyl-1,3-butadiene (2) compared to its BF3 diene counterpart, which is also consistent with our observations. In addition to enhanced Diels–Alder reaction rates, we also noted

• –Alder reactions that we have prepared to date. We have also demonstrated that this boron-substituted diene can serve as a synthon for a host of organic dienes via cross coupling reactions which we performed on Diels–Alder reaction cycloadducts. Experimental Preparation of 1,3-butadiene-2-diethanolamine

Synthesis and Diels–Alder cycloaddition reaction of norbornadiene and benzonorbornadiene dimers

• Bilal Nişancı,
• Erdin Dalkılıç,
• Murat Güney and
• Arif Daştan

Beilstein J. Org. Chem. 2009, 5, No. 39, doi:10.3762/bjoc.5.39

• cycloaddition reaction of dimers with TCNE and PTAD was investigated and new norbornenoid polycyclics were obtained. All compounds were characterized properly using NMR spectroscopy. Keywords: benzonorbornadiene; Diels–Alder reaction; norbornadiene; Stille coupling; Introduction Norbornadiene (1) and related

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• disconnection 3.1. Danishefsky. Mitomycin K (MMK) The retrosynthetic approach of Danishefsky is based on an intramolecular Diels–Alder reaction between a nitrosoaryl and a suitably functionalized diene (Scheme 7) [19]. Historically, this strategy was designed to synthesize the related natural product FR-900482

• introduction of the N-methyl aziridine in only three steps from an olefin by cycloaddition of methylthiophenyl azide onto the unsaturated amide 29. As mentioned before, the construction of FR-900482 was thought to occur by intramolecular hetero Diels–Alder reaction of a compound of type 32 (Scheme 8) [51

• ]. After careful analysis, it was envisioned that the reaction could occur either in the bridged mode to give the FR series (compounds 3 and 4) or in the fused mode to give access to mitomycins. Further investigations confirmed that the intramolecular hetero Diels–Alder reaction favoured the fused mode and

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• activity was investigated in benzyl ester cleavage, nitroarene reduction and a Diels–Alder reaction. The modified flavins photocatalyze the reactions, but the introduced substrate binding site does not enhance their performance. Keywords: flavin; guanidine; Kemp’s acid; photocatalysis; template

• )2, mono-Boc guanidine, CH2Cl2, rt, 20 h, 58–82%, (iii) HCl/Et2O, CH2Cl2/CHCl3, rt, 24 h, 83–90%. Oxidative photocleavage of dibenzyl phosphate. Photoreduction of 4-nitrophenyl phosphate. Photo Diels–Alder-reaction of anthracene with N-methyl-maleinimide. Oxidative photocleavage of dibenzyl phosphate

• . Results of nitrobenzene photoreduction. Results of photoinduced Diels–Alder-reaction. Supporting Information Photocatalytic experiments, UV/Vis and fluorescence spectra of 1–3, calculated gas phase conformations, 1H and 13C NMR spectra of 1, 2, 6, 7, 9, and 10. Supporting Information File 33

Reversible intramolecular photocycloaddition of a bis(9-anthrylbutadienyl)paracyclophane – an inverse photochromic system. (Photoactive cyclophanes 5)

• Henning Hopf,
• Christian Beck,
• Jean-Pierre Desvergne,
• Henri Bouas-Laurent,
• Peter G. Jones and
• Ludger Ernst

Beilstein J. Org. Chem. 2009, 5, No. 20, doi:10.3762/bjoc.5.20

• donor and an acceptor partner, such as a Diels-Alder reaction (see below). 3.3 Photodissociation Under the same experimental conditions, the photoproduct 4 was irradiated at 306 nm for 10 min until the starting material spectrum was recovered (Figure 8). Disappearance quantum yield of 4 at 306 nm was

• for MCH solution in Figure 9. One observes a drop of 50% absorbance after 8 cycles for MCH and 5 cycles for CH3CN (not shown). The photolysis at 306 nm must involve one or several photoreactions leading to products transparent at 392 nm. Thermal dissociation (a retro Diels-Alder reaction, see below

Synthesis of 2,3,6,7-tetrabromoanthracene

• Christian Schäfer,
• Friederike Herrmann and
• Jochen Mattay

Beilstein J. Org. Chem. 2008, 4, No. 41, doi:10.3762/bjoc.4.41

• and Chou presented the first synthesis of 2,3-dibromoanthracene [5], using a Diels-Alder reaction as the key step in synthesis. Twelve years later, Bowles and Anthony published an alternative synthesis for the same compound using a Bergman cyclization [6]. There are several other publications

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• Cope rearrangement and an intramolecular Diels-Alder reaction. The substrate for the Cope rearrangement was prepared by the merger of two cyclopentene units (Scheme 1). First, the addition of chloro compound 8 [18] to aldehyde 9 [19] occurred smoothly using the CrCl3/LAH system, developed by Hiyama et

• synthesis of compound 22 began with double alkylation of (+)-21 through a cuprate conjugate addition followed by treatment of the resulting enolate with methyl iodide (Scheme 5). Retro-Diels-Alder reaction of 22 in refluxing 1,2-dichlorobenzene gave α,β-unsaturated ketone 23. Trisubstituted cyclopentanone

• NaBH4) of the nitrile, MOM protection of the newly formed primary alcohol, and hydrolysis of the dioxolane gave ketone 30 and occurred as a prelude to retro-Diels-Alder reaction of the latter, leading to the α,β-unsaturated ketone 31. Compound 32 was obtained by treatment with LDA and Mander’s reagent

C₂-symmetric bisamidines: Chiral Brønsted bases catalysing the Diels- Alder reaction of anthrones

• Deniz Akalay,
• Gerd Dürner,
• Jan W. Bats and
• Michael W. Göbel

Beilstein J. Org. Chem. 2008, 4, No. 28, doi:10.3762/bjoc.4.28

• Brønsted bases in the Diels-Alder reaction of anthrones and N-substituted maleimides. High yields of cycloadducts and significant asymmetric inductions up to 76% ee are accessible. The proposed mechanism involves proton transfer between anthrone and bisamidine, association of the resulting ions and finally

• a cycloaddition step stereoselectively controlled by the chiral ion pair. Keywords: Asymmetric Catalysis; Bisamidines; Brønsted base; Diels-Alder reaction; Organocatalysis; Introduction The cycloadditions of anthrones 1 and N-substituted maleimides 2 are prominent examples of asymmetric catalysis

• °C (Table 3). Having identified suitable experimental conditions, we explored the scope of the bisamidine-catalyzed Diels-Alder reaction. The results are summarized in Table 4. Both electron-donating and electron-withdrawing substituents were tolerated and furnished products in good to excellent