Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• )-furanones from activated alkenes and 4-chloroacetoacetates (Scheme 1) [40]. The reaction was found to be general for a wide range of alkenes derived from aromatic and aliphatic aldehydes. The reaction proceeded via Michael addition of the acetoacetate to the alkene with a subsequent palladium-catalyzed ring

• closure of the primary adduct to form the furanone. In this paper, we report our investigations that extend the reaction to heteroatom-containing electrophiles such as imines and diazo esters. Results and Discussion Following the work on nitrostyrenes, Yan et al. also reported a two-step asymmetric route

• uncatalyzed pathway. The second step of the catalyzed route involves the oxidative addition of Pd(0)Ln to the C–Cl bond of Mannich adduct 16 to form 17. The oxy-π-allylpalladium intermediate 18 can then be formed from intermediate 17 [4][5][6][7][8]. The final step of the catalyzed mechanism, i.e., the ring

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• pathway (route I) proceeds without ring opening and after re-protonation it leads to the major cis-isomer 12. The minor route (route II), accompanied by a ring opening of the benzopyranone, proceeds via intermediate IIc, which after ring closure and protonation yielded a mixture of 2a and 13. This

• BF3 complexation as confirmed by the complexation energies (Table 3). Following complexation, the D-ring opening proceeds (Scheme 6), allowing molecular rearrangements and isomerization after ring closure. The observation of the isomerization of 1 (or 2) at C-11 that occurs in EtOAc but not in DMF can

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• phenyl group. The next step of the sequence, a ring closure to indenocircumtrindene (25), was accomplished by FVP. The bromine in the ortho-position of the phenyl group is presumably lost by homolytic bond cleavage, and the resulting aryl radical then cyclizes [6]. Unfortunately, the reaction also

• generates a significant amount of circumtrindene by loss of the phenyl group during the FVP process [58]. In an effort to improve on the yield over the FVP process, solution-phase ring-closure methods were also examined. All attempts to close 29 to indenocircumtrindene (25) by intramolecular arylations

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

• and strongly basic conditions [19]. Kang et al. achieved a highly enantioselective synthesis of an isoindolo[2,1-a]quinoline derivative by affecting an intramolecular ring closure on (E)-3-(2-(isoindolin-2-yl)phenyl)acrylaldehyde using camphorsulfonic acid and a chiral pyrrolidine organocatalyst [20

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• -ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single

• crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis). Results of DFT calculations are presented

• -ylidene with acetylenes. Indazol-3-ylidenes which possess an aryl ring at N1 rearrange to give substituted acridines by a ring-cleavage/pericyclic ring-closure reaction sequence (2→A→B→11) (Scheme 3). It proved to be advantageous to start these rearrangements from indazolium salts which are readily

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• stereoinduction was observed for the newly formed stereocenter (dr 1:1). As an extension, the authors performed the Ugi reaction with allyl amine 79 and olefinic amino acids 78 (derived from pyroglutamic acid), that, after a following ring-closure-metathesis (RCM) with Grubb’s catalyst, resulted in bicyclic

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

• Murat Kucukdisli,
• Dorota Ferenc,
• Marcel Heinz,
• Christine Wiebe and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 466–470, doi:10.3762/bjoc.10.44

• )nitriles can be used as versatile and readily accessible pronucleophiles, e.g. for the construction of γ-amino acids [32], pyrrolidines [33], as well as pyrroles [34][35]. If an additional conjugated double bond is present, the anions of α-(alkylideneamino)nitriles 3 can undergo an electrocyclic ring

• closure to furnish 3,4-dihydro-2H-pyrrole-2-carbonitriles 6 after reprotonation [36]. If the products are devoid of an additional substituent in 2-position, the cyclocondensation can be simply effected by refluxing a mixture of the enone 1 and aminoacetonitrile hydrochloride (2) in pyridine. The base

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

• products containing a dihydrooxepine moiety. In the case of occidenol (25, see Scheme 5), which has been isolated from the wood of Thuja koraiensis, farnesyl pyrophosphate (22) is supposed to undergo ring closure and the intermediate carbocation is trapped by hydroxide to give hedycaryol (23) [33

• kinetic resolution [156], albeit with unsatisfactory enantiomeric excess. The undesired enantiomer was then selectively cleaved using another enzyme with reversed selectivity to give enantiopure pyranone 181. Cyclopropanation was achieved using a Michael addition initiated ring closure yielding diester

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• substituent, are inert under the reported conditions. Haloperoxidation reaction that is accompanied by intramolecular ring closure represents another version of the cyclization reaction. For example, the reaction of bromine with unsaturated hydroperoxide 146 (produced by reaction of 1,4,5,8

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• isocyanides to Lewis acid-activated imines (Scheme 3). The first nitrilium intermediate can evolve through a second addition and ring-closure to yield the azetidine adduct 3 (Scheme 4, route i), or can also be trapped by water or amine/imine nucleophiles leading to α-aminoamides 7 and α-aminoamidines 4

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• , followed by two kinds of library diversification involving 1) Michael addition of a set of primary amines and the subsequent nucleophilic ring closure to give the difluoroquinolone system, 2) intermolecular nucleophilic aromatic substitution with various amines and hydrolysis of ester moieties to afford a

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

• spontaneous desulfurization and convert into tetrasubstituted alkenes [20]. 2) Pathway B assumes a stepwise cycloaddition of the diazo-1,3-dipole with the C=S bond leading to the initial formation of the diazonium zwitterion 11. This step is followed either by the ring closure to give thiadiazoline 10 or by

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• -containing ketimine, with benzyloxyketene in a conrotatory ring closure process. Imine formation and cyclization were possible in spite of the acidification of protons on the carbon bound to SF5. The reactions of the aldimines demonstrated very good 1,2-lk diastereoselectivity, however lack of stereochemical

• ]. Structural characterization of SF5-containing β-lactams Isolated as a single diastereomer, the relative stereochemistry of 7a, the product of the Staudinger reaction of 5a, is shown in Figure 1. The cis relative stereochemistry of β-lactam is consistent with 1,2-lk conrotatory ring closure of the E-imine 5a

• increases the acidity of the α-proton of the imine 5 and of the iminium ion intermediate B formed on the initial nucleophilic attack of the imine on the ketene as illustrated in Scheme 4. The ring closure step requires bond formation between the iminium ion carbon and the enolate carbon B to be particularly

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• , ring closure (IV) and deprotonation to isomeric 1,2,4-triazolo[1,5-c] pyrimidine 6 (Scheme 2). Indeed, small quantities of the triazole 6 can be observed by 1H NMR and thin-layer chromatography in our original attempts to isolate pure 5. Although very slow, the rearrangement of the triazole 5 to 6 was

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• malononitrile) and bypass the pyridone intermediate used in the original CAPIC synthesis (Scheme 2a) by effecting the ring closure under Pinner reaction conditions (Scheme 2b) [14]. We set out to investigate the possibility of performing a continuous synthesis of 2-bromo-4-methylnicotinonitrile starting from

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation. Keywords: dienes; enzyme catalysis; lactones; metathesis

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• moiety, independently of the mechanism (concerted fashion or via Michael-like transition state followed by a Mannich-like ring closure in a stepwise mechanism yields the same cycloadduct) [38]. This fact is assumed to be a consequence of the unsymmetrical electron density in the 1,3-dipole moiety, being

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess–Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure

• ; ring closure; trans-methylation; Introduction Pumiliotoxins (PTXs, 1, Figure 1) such as pumiliotoxin 251D (2) are a subclass of indolizidine alkaloids isolated from the skin secretion of neotropical frogs. A total of 19 members have been isolated and partially characterized [1]. Pumiliotoxins are

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

• in xylenes undergoes ring-closure yielding the desired pyrimidine 3.22 but unfortunately only in modest yield. However, this key intermediate could be readily N-methylated, and in a simple extension to the sequence subjected to direct amide formation, debenzylation and finally coupled with the

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• [49]. The proposed mechanism is based on the generation of a gold(I)-activated allene, which undergoes a cyclization to give a new carbocationic species of type VI (Scheme 7) [50][51]. A subsequent ring closure provides the observed bicyclo[3.2.0] systems of type 12, featuring a four-membered

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

• approach and subsequent ring closure. During this process two of the four rings of the anthracycline scaffold are formed. Differently substituted carbohydrates and dialkyne chains serve as versatile and simple starting materials for the reaction sequence. Diverse building blocks lead to a variety of

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• , showed a notable antinociceptive and anti-inflammatory activity without toxic side-effects. Keywords: antinociceptive/anti-inflammatory agents; imidazophosphor esters; phosphonyl carbanions; ring closure; tetrazolo[1,5-b]pyridazine; Introduction Inflammation is a characteristic feature of disease

• carbanion 2a or 2b on the azido-function in 1b yielding the phosphonate intermediate 3 along with the evolution of a nitrogen molecule. Subsequent intramolecular ring closure, the fused imidazolo-phosphonate 4 would be obtained under elimination of an appropriate alcohol moiety. In the same fashion, the

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3. Keywords: dehydration of oximes; flow chemistry; gallium; microreactors; Lewis acid catalysis

• -hydroxy group and the oxime to give ring closure to the corresponding oxazoles 11 and 12, respectively, in very good conversions. The dehydration of 1 (25 µM in acetonitrile), under similar conditions as mentioned above, was used to test the stability of the catalytic layer in the microreactor. When the

• nitriles and the ring closure of ortho-hydroxy oximes to the corresponding oxazoles. In general, our catalytic system showed faster conversions for most substrates than using lab scale conditions. XPS data, obtained on a flat silicon oxide surface, showed that on average one gallium per 2–3 styrene

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• diradical 9 [27]. The latter can then either undergo ring closure to form indan-2-one (IN), or decarbonylate to give o-xylylene (XY). The equilibrium of XY and benzocyclobutene (BC) is established in the literature [28], as well as the formation of styrene ST from BC [29]. An alternative mechanism, the