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

• the N-aryl group undergo intramolecular electrophilic addition to the alkene yielding isoindolo[2,1-a]quinolines under acidic conditions [18]. Isoindolo[2,1-a]quinolone cores have also been prepared via an aldol-type intramolecular cyclization reaction of N-(2-acetylaryl)phthalimide under anhydrous

• the same fate of condensation without further electrophilic aromatic substitution. Lu et al. [43] have recently reported the synthesis of 3-(1-alkenyl)isoindolin-1-ones from N-acyliminium cations; however, their intermediates did not have the opportunity for intramolecular cyclization. The nitrogen

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• -pyrazole-4-carboxylate (5c) [14][15][16][17][18]. The Reaction of enol ethers 3b and 3c with hydrazine hydrate at rt for 10 min gave products of an SNV reaction, 4b and 4c. These then underwent intramolecular cyclization to yield 5b and 5c. Due to oxo–enol tautomerism eight tautomers are theoretically

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• synthesized in two steps at room temperature, first, by a nucleophilic attack of methyl hypophosphite on oxazolidine 60 followed by an intramolecular cyclization, this time without base catalyzed transesterification. The authors explained this difference of reactivity by the Thorpe–Ingold effect [38]. Indeed

• , the presence of four methyl groups allows the hydroxy function to be spatially closer to the reactive phosphinate, facilitating the intramolecular cyclization of this product. Conclusion Phosphinate heterocycles are becoming routine products in the literature. Classical approaches such as the

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

• aldehydes and carboxylic acids [106]. Subsequent TFA-treatment provided the precursor 125 that via a follow-up reaction with Lawesson’s reagent and an intramolecular cyclization gave access to the thiazole derivative 126. A second TFA-cleavage of the N-(1,1,3,3-tetramethylbutyl) group resulted in the 5

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• -carboxaldehydes and its byproduct. Key steps of the process are the silver-catalyzed intramolecular cyclization of propargylamine followed by a competitive 1,3- or 1,5-isomerization and a subsequent hydrolysis, yielding the pyrroloimidazolone 5 or the pyrrole 4, respectively (Scheme 5). The 1,5-isomerization path

• (Scheme 33) [90][91]. The reaction occurs via a Mannich-type addition of the deprotonated isocyanide intermediate 64 to an in situ generated iminium salt, a subsequent intramolecular cyclization and proton shift results in dihydroimidazole 65 showing predominantly cis-arrangment around the C4–C5 bond

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• of iminium ion 8. Finally, an intramolecular cyclization of 8 leads to the formation of 9 which subsequently undergoes deaminative elimination to result product 5 by releasing the amine catalyst for further recycling (Scheme 3). Conclusion In conclusion, we have established an unprecedented amine

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• photocyclization [22], intramolecular cyclization of the aldehyde 27 was considered for the preparation of gigantamide A (7). The aldehyde 27 in turn could be prepared from dasyclamide (6). Conditions and results for the oxidation of dasyclamide (6) to give gigantamide A (7) are outlined in Table 1. The results

• ) was achieved with the aid of a Baylis–Hillman adduct. We have also demonstrated a one-step conversion of dasyclamide (6) to gigantamide A (7) by oxidative intramolecular cyclization by using PCC. Bisamides as building blocks for flavaglins. (+)-Grandiamide D, gigantamide A and dasyclamide

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

• main methods for the preparation of peroxides from alkenes. Compounds (oxidized by the Isayama–Mukaiyama reaction) containing a reaction center that can be subjected to the attack by a peroxide radical, are able to undergo intramolecular cyclization to form the 1,2-dioxolane ring. For example, the Co

• peroxide functional group. As in the above-considered studies, the intramolecular cyclization of ozonolysis products can be performed with the use of the hydroperoxide group provided that there is an appropriate electrophilic center. The reaction of oxetanes 60a,b with ozone in methanol produced 3-alkoxy

• total yield of 48% (Scheme 26) [256]. These syntheses of dioxolanes involve the formation of the peroxycarbenium ion as the key step. The reaction of the latter with allyltrimethylsilane followed by the intramolecular cyclization finally leads to the dioxolane ring. Dioxolanes 99–102 are produced from

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

• isatinimines led to the formation of the spiro-azetidines 3k (14%) and 3l (28%, Table 1, entries 11 and 12). Remarkably, in the former case an intramolecular cyclization of the nitrilium ion upon the electron rich p-methoxyphenyl group took place and led to the formation of the bis(imino)tetrahydroquinoline 8

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• (lithium (trimethylsilyl)acetylide, THF, −60 °C → −50 °C or lithium phenylacetylide, THF, −78 °C) afforded derivatives 6a–c and carbamates 7a–c as mixtures of diastereomers (Table 2). It should be mentioned that upon storage at room temperature derivatives 6a–c undergo slow intramolecular cyclization to

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• experiments were performed by employing 1a as the model substrate in order to optimize the intramolecular cyclization conditions for ligands, bases, solvents, temperature and time. As shown in Table 1, the reaction was initially carried out with CuI as the catalyst, L1 as the ligand, and K3PO4 as the base in

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• -catalyzed oxidative lactonization or an intramolecular cyclization reaction of δ-ketoaldehydes [12], a ruthenium-catalyzed aerobic oxidative cyclization of aromatic acids with alkynes [13], an FeCl3-promoted regioselective annulation of o-(1-alkynyl)benzoates with disulfides [14], a Heck–Matsuda cyclization

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

• using any of the chiral bisgold complexes derived from (R)-C1-Tunephos (Au19) or (R)-MeO-DTBM-Biphep (Au5) (Scheme 17) [85]. From a mechanistic point of view, the authors proposed the generation of a zwitterionic furanylgold complex of type XIII by a gold-promoted intramolecular cyclization process

• . This key intermediate is then trapped by the nitrone to afford XIV, which eventually evolves to the product by an intramolecular cyclization (Scheme 17). Finally, the same group recently reported a related reaction of 1-(1-alkynyl)cyclopropyl ketones such as 28, by means of a gold(I)-catalyzed

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• substituents at the benzene ring were prepared by acid-catalyzed photoinduced cyclization of phenylazopyridines [5]. Recently, we demonstrated an efficient alternative method for the formation of 1a and other parent tricyclic azinium cations of general structure I (A = B = H) by light-induced intramolecular

• cyclization of fluorides II (Figure 1) in the presence of Ca2+ ions [7]. A further progress in the investigation of cation 1a and its applications as a pharmacophore or a component of organic materials requires access to functionalized derivatives, in which substituents control the properties and allow the

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

• conjugated reaction between 3,6-diazidopyridazine and different types of phosphonyl carbanion reagents followed by intramolecular cyclization afforded the target products, by using sodium ethanolate solution as a reaction medium. Among the products, five compounds, at a dose of 50 mg per kilogram body weight

• intramolecular cyclization led to the product 7 (Scheme 2). Conversely, similar treatment of 1b with diethyl (methylthioalkyl)phosphonates 8a and 8b under the same reaction conditions yielded the fused diazaphospholo-substituted compounds 10a and 10b in 72 and 74% yield, respectively. The 31P NMR spectrum (CDCl3

• the intermediates 9a or 9b accompanied by the elimination of a N2 molecule. Further intramolecular cyclization of 9 afforded the diazaphospholes 10a and 10b, respectively, through the loss of an ethanol molecule [31] (Scheme 3). Next, the fused imidazophosphono-substituted compound 13 (68% yield) was

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• intramolecular cyclization. The significantly lower oxidation potential measured for 19c relative to that measured for its seven-membered ring counterpart 19d was again consistent with a fast initial cyclization. We believe that the primary advantage of the methoxy group is to facilitate the second electron

Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

• Brian M. Casey,
• Dhandapani V. Sadasivam and
• Robert A. Flowers II

Beilstein J. Org. Chem. 2013, 9, 1472–1479, doi:10.3762/bjoc.9.167

• 73% yield. To examine the breadth of this method, a series of δ-aryl-β-dicarbonyl substrates was prepared by a previously reported procedure [17]. As shown in Table 1, the intramolecular cyclization of δ-aryl-β-diketones with unsubstituted aryl rings (Table 1, entries 1 and 3) afforded 2-tetralone

• ring of the starting material [10][11]. To probe the impact of electron density of the δ-aryl ring on intramolecular cyclization, several substrates with either electron-donating or electron-withdrawing groups were synthesized and subjected to our reaction conditions. The results of these experiments

• a consequence, these radicals should favor coupling with more nucleophilic, electron-rich carbon centers. The observation that intramolecular cyclization did not occur in either of the electron-deficient substrates (compounds 1h and 1i) is consistent with electrophilic radical intermediates. To

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• a 6-endo intramolecular cyclization of the imine to produce the cyclized product. The second step is the rate-limiting step and the electrophilicity of the imine is the driving force of the cyclization. HCl generated in situ from TCT protonated the imine intermediate to an iminium ion, which

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• provided evidence that these byproducts were generated by the intramolecular cyclization of enone 10 with TMSCl in EtOH, suggesting that the FeCl2/TMSCl system also gave enone 10 in ca. 30% yield [37]. The present study on the aminohalogenation reaction of carbamate 8 has inspired mechanistic insights that

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• of salicylaldehyde (5) with dimedone (18) in the presence of a catalytic amount of KF/Al2O3 (Scheme 6) [21]. The reaction is thought to proceed through a Knoevenagel condensation, a Michael addition and an intramolecular cyclization. The reaction was repeated with chloro-, bromo-, dichloro-, dibromo

• synthetic procedures involve a Knoevenagel condensation followed by intramolecular cyclization. In a detailed study directed towards understanding the pathway of the reaction of salicylaldehyde (5) and malononitrile (20), Costa and co-workers reported the efficient synthesis of 2-iminochromene 21 in 90

• cascade reaction of salicylaldehyde (5) and malononitrile (20) involving an aldol reaction followed by intramolecular cyclization and finally a dehydration to give intermediate 21. A subsequent Michael addition of the indole (25) to intermediate 21 gives cation 26, which loses a proton to give the product

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• transformation will involve Sharpless asymmetric dihydroxylation to install stereoselectively the hydroxy groups at C3 and C4 positions of the olefinic substrate 6, and an intramolecular cyclization of aldehyde generated in situ from 5 to construct the piperidine ring system. The present publication describes

• followed by spontaneous intramolecular cyclization with a yield of 67%. The structural identity of this product was precisely confirmed by 1H NMR spectroscopic data, which proved to be in good agreement with those on record for 4 [19]. Hence, we can conclude that a formal total synthesis of

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• -indolyl allenamides. Amidation reaction of 1-allyl-2-indolecarboxamides. Intramolecular cyclization of N-benzoylindole. Intramolecular alkenylation/carboxylation of alkenylindoles. Intermolecular alkenylation/carboxylation of 2-substituted indoles. Mechanistic investigation of the cyclization

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• similarity to the process shown in Scheme 1. However, when the reaction of 3 with CO (1 atm) is performed in MeOH, a mixture of the compounds derived from intramolecular cyclization (4) and alkoxycarbonylation (5) is obtained (molar ratio 4/5 2.4:1). This mixture can be separated by column chromatography

• attempted several reaction conditions in order to prepare selectively compound 5, but it seems to be difficult to quench the intramolecular cyclization, and in all studied cases the 4/5 mixture is obtained. Due to this fact, we have not studied other alcohols. Conclusion The reactivity of the

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• substructures and subsequent intramolecular cyclization between these substructures to form the fused skeletons (Figure 1c). As a pioneering approach to shape the foundation of the “Build-Couple-Pair” (B/C/P) strategy [7][8][9][10][11][12][13][14][15] for diversity-oriented synthesis [16][17], a synthetic