Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• electron-demand Diels–Alder reaction from 1,2,4-triazines bearing an acylamino group with a terminal alkyne side chain. Alkynes were first subjected to the Sonogashira cross-coupling reaction with aryl halides, the product of which then underwent an intramolecular inverse electron-demand Diels–Alder

• reaction to yield 5-aryl-3,4-dihydro-1,8-naphthyridin-2(1H)-ones by an efficient synthetic route. Keywords: inverse-electron-demand Diels–Alder reaction; microwave irradiation; naphthyridin-2(1H)-ones; Sonogashira cross-coupling; 1,2,4-triazine; Introduction 1,8-Naphthyridine derivatives are an important

• -demand Diels–Alder reaction under microwave irradiation [22][23][24]. The use of 1,2,4-triazines in inverse electron-demand Diels–Alder reactions proved to be an efficient strategy for the construction of various heterocyclic compounds [25][26][27], such as azacarbazoles [28][29][30][31][32][33

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

• heterodienes have also been successfully used as key elements in such strategies. In this review, we focus on the most significant results and recent contributions obtained in this area [27][28]. Review 1-Boron-substituted 1,3-dienes The first Diels–Alder reaction involving a 1-boron-substituted 1,3-diene was

• boronated dienes 6, which were not isolated, but directly used in a one-pot Diels–Alder reaction/allylboration sequence. This efficiently generated, in high yields, tricyclic structures 7 with control of four stereogenic centers created (Scheme 8). In the presence of Grubbs II catalyst, a skeletal isomer 8

• was produced from 5. If the [4 + 2]-cycloadduct 9 was obtained with N-phenylmaleimide, it failed to give homoallylic alcohols, probably due to steric hindrance [42]. An elegant three-component process was developed by Hilt and co-workers using a cobalt-catalyzed Diels–Alder reaction as the key step in

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• was achieved using TBAF, followed by formation of a vinyl triflate and Stille coupling with tributyltin hydride. The oxidation state of the remaining ester was adjusted to the corresponding aldehyde, followed by a Lewis acid-catalyzed intramolecular inverse-electron-demand hetero-Diels–Alder reaction

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• reacts with thioketone 1a in a Diels–Alder reaction, and 1,3-oxathiinone 4b is formed as a [4 + 2]-cycloadduct (Scheme 3). The major product of the reaction of diazomalonate 2е with thioketone 1а is temperature dependent. Thus, mainly 1,3-oxathiole 3е is formed at room temperature, while alkene 5е was

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

• very fruitful for the preparation of 1,3-dienes, this protocol has remained almost unexplored for propargyl fluorides [26]. In this context, we have recently established a tandem multicomponent protocol CEYM–Diels–Alder reaction of several difluoropropargylic derivatives [27][28] mediated by 1,7

• -octadiene as an internal source of ethylene [29]. Following our ongoing interest in the use of these fluorinated building blocks, we decided to evaluate the CEYM reaction of several difluoropropargylamides and ketones in combination with a Diels–Alder reaction under Mori´s conditions, in order to compare

• probably due to the fact that under those thermal conditions, it is not possible to use these types of dienophiles since they decompose while being heated. The sequential generation of the dienic intermediate 2 and the Diels–Alder reaction allow performing the second step at rt, avoiding these problems

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• R-(+) form, the S-(−) form or the racemate leading to the conclusion that an enantioselective synthesis leading to solely S-(−)-amlodipine would be beneficial only if economically feasible [67]. An alternative strategy to this molecule begins with an interesting aza-Diels–Alder reaction between the

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• lack of efficient synthetic approaches to anthracyclines many industrial approaches still rely on the use of recombinant microorganisms with a mutated gene of the anthracycline metabolism [9]. Different convenient synthetic transformations involve the application of a Diels–Alder reaction as key step

• -Diels–Alder reaction of an aryldiacetylene system (Scheme 2) [15]. Compound 7 reacts at high temperature in a mixture consisting of toluene and triethylamine to an inseparable mixture of cyclized diol (52%) and quinone 8 (36%). Quantitative oxidation of the diol by MnO2 provided the desired tetracycle 8

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• substitution patterns. We were also interested in determining the double bond specificity of the Denmark Diels–Alder reaction for unsymmetrical dienes. Previous work on cyclopentadiene and cyclohexadiene has shown that the reaction can be quite specific to give one of two possible regioisomers [11][12]. In the

• –Alder reaction) [1][11][12]. Other methods of nitronic ester preparation are known and ongoing studies in our laboratory directed at an application to O-allyl nitronic ester synthesis will be reported elsewhere. In continuing our investigations, we desired additional O-allyl nitronic esters with varied

• been the subject of several theoretical investigations [7][8][9][10]. The necessary nitronic ester precursors are readily preparable by Lewis acid-promoted [4 + 2]-cycloaddition reactions of nitroalkenes with appropriate dienes, a general reaction first reported by Denmark and coworkers (Denmark Diels

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

• reported, which were reviewed by Hertweck and Bräse [44][58]. In line with the focus on the construction of the isoindole component, one can identify the Diels–Alder reaction as the most popular strategy. A linear, biomimetic synthesis using a late stage intramolecular Diels–Alder reaction was implemented

• 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

• using an intramolecular Diels–Alder reaction. The synthetic endeavor began with the conversion of dihydropyran 79 to the acetal 80 (Scheme 9). Activation of the anomeric position with tin(IV) chloride presumably led to the formation of the oxonium ion 81. This intermediate was envisioned to undergo a

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• same intrinsic reactivity of molecules. It is fascinating to see that a particular chemical reaction, believed to be invented by man, is in fact already used for millions – sometimes even billions – of years by Mother Nature. An interesting example is the discovery of the Diels–Alder reaction in the

• 1920s and its later enhancement into an enantioselective reaction by the development of chiral catalysts. But a Diels–Alder reaction also occurs in the biosynthesis of lovastatin and is likely catalysed by a Diels–Alderase [5], a natural analogue of man-made chiral catalysts! Beyond such fascinating

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

• presented. The reaction and the analytical separation are combined in a single experiment to investigate the Diels–Alder reaction of benzenediazonium-2-carboxylate as a benzyne precursor with various anthracene derivatives, i.e. anthracene, 9-bromoanthracene, 9-anthracenecarboxaldehyde and 9

• ; cycloaddition; Diels–Alder reaction; flow chemistry; gas chromatography; on-column reaction gas chromatography; Introduction The combination of synthesis and analysis in a single experiment offers many advantages. Time-consuming steps, i.e. work-up and separation of the reaction products, can be minimized, and

• our novel ocRGC setup, we chose the cycloaddition of benzyne with anthracene derivatives in a typical Diels–Alder-reaction (Scheme 1) as a model reaction. This reaction seemed suitable because of the volatility of all reactants and products and the required reaction temperature, which is in an

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

• -Leopoldshafen, Germany 10.3762/bjoc.9.158 Abstract A variety of organocatalysts were screened for the catalysis of the naphthoquinone monoketal Diels–Alder reaction. In this study we found that Schreiner's thiourea catalyst 10 and Jacobson's thiourea catalyst 12 facilitate the cycloaddition of the sterically

• tricycle of beticolin 0 (1) and is also a valuable model substrate for the total synthesis of related natural products. Keywords: beticolin 0; Diels–Alder reaction; natural product; organocatalysis; thiourea catalysis; total synthesis; Introduction In the past few years, many different types of

• organocatalysts were found to accelerate a variety of reactions. Due to the value of the Diels–Alder reaction for the synthetic community, different organocatalysts have been developed to catalyze this atom-economical cycloaddition in a highly enantioselective fashion. Thereby, chiral amines, heterocyclic

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

• diffraction experiment. Keywords: chiral heterodiene; hetero-Diels–Alder reaction; pyrrolizidin-3-one; solvent effect; tandem reaction; Introduction Conjugated nitroalkenes play an important role in cycloaddition reactions providing useful nitrogenated cycloadducts with varied synthetic applications (Scheme

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• Toshiki Tabuchi Daisuke Urabe Masayuki Inoue Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 133-0033 Japan 10.3762/bjoc.9.74 Abstract The stereoselective Diels–Alder reaction between an optically active 1,4-dimethylcycloheptadiene and acrolein was

• synthesis; C2-symmetry; catalysis; Diels–Alder reaction; Lewis acid; natural product; quaternary carbon; Introduction Ryanodine (Scheme 1) [1][2][3] is a potent modulator of the intracellular calcium release channels, known as ryanodine receptors [4][5]. Its complex architecture, including eight contiguous

• steps. Bicyclo[3.3.2]decene 1 was prepared from C2-symmetric bicyclo[2.2.2]octene 2 through a ring-expansion reaction (Scheme 1) [11]. We reported the synthetic routes to racemic 2 and enantiomerically pure 2 from 3 and 5, respectively. Specifically, the dearomatizing Diels–Alder reaction between 2,5

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

• , Germany 10.3762/bjoc.9.40 Abstract The Diels–Alder reaction of the 2-phosphaindolizine-η1-P-aluminium(O-menthoxy) dichloride complex with dimethylbutadiene was investigated experimentally and computationally. The >C=P– functionality of the complex reacts with 2,3-dimethylbutadiene with complete

• barrier of the Diels–Alder reaction of 7a with 1,3-butadiene, involving its attack from the Si face, is lower. It is found that in this case, the exo approach of the diene is slightly preferred over the endo approach. Keywords: aluminium(O-menthoxy) dichloride; asymmetric synthesis; >C=P– functionality

• ; DFT calculations Diels–Alder reaction; Introduction There is an increasing emphasis on the synthesis of optically pure compounds, as far as possible, for environmental, economic and social reasons. Using chiral auxiliaries for changing enantiotopic faces into diastereotopic faces is a common approach

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• distillation is difficult because they are unstable und possess similar physical constants. If pure 21 were needed, 2 can be removed from the reaction mixture by trapping it by a Diels–Alder reaction (see Section 1.4.1 below). The analytically pure hydrocarbons were obtained by preparative gas chromatography

• phosphinidenes generated in situ from various stable precursors. For example, the tungsten-complexed pentacarbonyl complex PhP=W(CO)5, generated by heating 191 (retro-Diels–Alder reaction), provided the unexpected 3,4-disubstituted phosphole 192 (Scheme 45) [133]. Analogously, the phospholene complex 194

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

• reaction; tetrahydroquinoline; Introduction The Diels–Alder reaction is recognized as a powerful reaction in synthetic strategies for the production of natural and unnatural polycarbocycles and polyheterocycles [1][2][3]. Therefore, the hetero-Diels–Alder reactions and domino reaction procedures have been

• developed as the most powerful synthetic routes to construct oxygen or nitrogen-containing six-membered heterocycles [4][5][6][7][8]. In recent years, the imine Diels–Alder reaction (also known as Povarov reaction) and the [4 + 2] cycloaddition reaction of imines (obtained from the corresponding aromatic

• addition of intermediate A with the acid-promoted N-aryl aldimine B gives the intermediate C. Lastly, the intramolecular electrophilic aromatic substitution at the ortho position of the activated N-aryl ring gives the final tetrahydroquinoline 1. On the other hand, the concerted imine-Diels–Alder reaction

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

• Magnus Rueping and
• Sadiya Raja

Beilstein J. Org. Chem. 2012, 8, 1819–1824, doi:10.3762/bjoc.8.208

• Magnus Rueping Sadiya Raja Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.8.208 Abstract A new chiral Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene has been developed. The reaction provides

• optically active aza-tetracycles in good yields with high diastereo- and enantioselectivities under mild reaction conditions. Keywords: BINOL phosphate; [4 + 2] cycloaddition; Diels–Alder reaction; organocatalysis; Introduction The enantioselective aza-Diels–Alder reaction is an important method for the

• chiral Lewis acids [5][6][7][8][9][10][11][12][13][14][15][16]. Recently, chiral Brønsted acids have attracted interest as effective catalysts for a variety of asymmetric transformations involving imine electrophiles [17][18][19][20][21][22][23]. Among others, the aza-Diels–Alder reaction of imino

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

• and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The products were isolated in good yields. The mild catalysts did not cause

• the C(2) position as catalysts for the aza-Diels–Alder reaction [11][12]. These catalysts do not activate the substrate through hydrogen bonding, but instead, like other carbon-cation based catalysts, through their positive center [8][9][10][13][14][15], and belong also to the field of organocatalysis

• [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

• synthesis. Keywords: cannabinoids; Diels–Alder reaction; natural product synthesis; organocatalysis; Introduction The Diels–Alder reaction is one of the most important processes for carbon–carbon-bond formation in organic chemistry [1][2]. Especially in the synthesis of natural products it is a widely

• ]. Given the importance of the Diels–Alder reaction, considerable efforts have been directed towards increasing the reaction rate and enantioselectivity. In the past century, catalysts that were employed for the enantioselective synthesis of organic compounds, such as pharmaceuticals, agrochemicals, or

• enantioselective organocatalytic Diels–Alder reaction was reported by MacMillan in his pioneering work in 2000 [17]. The activated iminium ion, formed through condensation of imidazolidinone and an α,β-unsaturated aldehyde, underwent reactions with various dienes to yield [4 + 2]-cycloadducts in excellent yields

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

• Chunhui Dai,
• Bo Liang and
• Corey R. J. Stephenson

Beilstein J. Org. Chem. 2012, 8, 986–993, doi:10.3762/bjoc.8.111

• ; 1,3-dicarbonyl compounds; Diels–Alder reaction; molecular diversity; pyridine dearomatization; spirooxindole; Introduction The spirooxindole is a common structural motif found in a variety of complex alkaloids [1]. Many compounds that possess a spirooxindole moiety exhibit significant biological

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• library of annulated α-carboline structures 6 could be prepared by the intramolecular inverse electron demand Diels–Alder reaction (IEDDA) of isatin-derived 1,2,4-triazines 7 with tethered electron-rich dienophiles (Scheme 1) [69]. Inverse electron demand Diels–Alder cycloadditions employing electron

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