Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• Pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones 12 have been easily prepared via nucleophile-induced rearrangement of pyrrolooxadiazines 11 and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles 10. In this work, we demonstrated that the described synthetic approaches can be

• considered to be more facile and practical than previously reported procedures. Keywords: intramolecular cyclization; pyrrolooxadiazines; pyrrolotriazinone; rearrangement; Introduction Pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones have been considered to be biologically active compounds. For example, these

• °C in the presence of either NaOH or KOH [4][9], and heating with POCl3 [11] (Figure 2). It is reasonable to consider that these harsh conditions are required because it is difficult to form the N-imine structure and to subsequently perform intramolecular cyclization (Figure 2). In our efforts to

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• enolate 7 involved the 1,4-reduction of α,β-unsaturated ester 2 by 6 and the transmetalation with a zinc species to give the Reformatsky-type reagent Int A. This intermediate Int A reacts immediately with the imine to give the corresponding intermediate Int B. Subsequently, intramolecular cyclization of

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• converted to the heterocyclic bisphosphonate 137 through an intramolecular cyclization (Scheme 29) [55]. The sequenced reaction of the amine with triethyl orthoformate followed by the addition of sodium diethylphosphite dissolved in toluene considerably increased the yields of bisphosphonates. In this way

• phosphorylated heterocycles is the condensation of an activated methylene component with a carbonyl compound followed by subsequent transformations such as intramolecular cyclization, Michael-type addition and hetero-Diels–Alder cycloaddition. 3.1 Domino Knoevenagel/phospha-Michael process A convenient one-pot

• the phospha-Michael adducts were converted to new phosphorylated heterocycles through intramolecular cyclization reactions. The phospha-Michael adduct 149 resulting from the three-component reaction of 6-methyl-3-formylchromone with malononitrile 145 or 2-cyanoacetamide 148 and diethyl phosphite is

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• dications can either undergo an intramolecular cyclization to 4-arylquinolin-2(1H)-ones 3 or, alternatively, react with arenes as external π-nucleophiles. In this latter pathway, Friedel–Crafts alkenylation of arenes by species A leads to structures 4, which can then be diprotonated to the cations B and

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• anti-aldolate A1, possessing ΔGrel of −6.60 kcal mol−1. In the next step, A1 is attacked by a second enolate at higher temperature via the bicyclic transition state TS-A1-A2 (ΔGrel = 4.18 kcal mol−1) with a chair–chair conformation. In the last step, intramolecular cyclization with a relative TS energy

Syntheses of dibenzo[d,d']benzo[2,1-b:3,4-b']difuran derivatives and their application to organic field-effect transistors

• Minh Anh Truong and
• Koji Nakano

Beilstein J. Org. Chem. 2016, 12, 805–812, doi:10.3762/bjoc.12.79

• desired syn-DBBDF 5 was successfully synthesized via the double intramolecular cyclization under basic conditions at high temperature (92% yield) [37][43]. The same synthetic strategy was applied to the synthesis of syn-DNBDF (Scheme 2). 2-Decyl-7-methoxynaphthalene was prepared from 7-methoxynaphthalen-2

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• nascent chain, resulting in off-loading. 2.4 Biosynthesis by free-standing ketosynthases In contrast to the α-pyrone formation by intramolecular cyclization reactions, also the condensation of two polyketide chains can result in a pyrone ring. Such a mechanism was indicated by feeding experiments for the

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• -triflyloxyindole was preferred over a 5-bromoindole, because 2-iodo-5-methyl-4-nitrophenol (11, Scheme 3), to be used in the Batcho–Leimgruber protocol, appeared to be more readily accessible than 1-bromo-2-iodo-5-methyl-4-nitrobenzene. Moreover, aryl triflates have been used in intramolecular cyclization

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• /bjoc.12.32 Abstract An oxidative reaction for the synthesis of 4-alkyl-substituted dihydroisoquinolin-1(2H)-ones with N-allylbenzamide derivatives as starting materials has been developed. The radical alkylarylation reaction proceeds through a sequence of alkylation and intramolecular cyclization. The

• . Intermediate C proceeds through intramolecular cyclization to give intermediate D. Finally, H-atom abstraction occurs between D and TBPB directly, which gives the product 5aa and regenerates radical A for the next cycle. Conclusion In summary, a metal-free cascade functionalization of unactivated C(sp3)–H

• bonds and cyclization reactions of N-substituted allylbenzamides were developed. The reaction involved cleavage of the C(sp3)–H bond, alkylation and intramolecular cyclization, affording the 4-alkyl-substituted dihydroisoquinolin-1(2H)-one derivatives with moderate to good chemical yield. The

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• also been widely used as chiral ligands and auxiliaries in asymmetric synthesis [3]. Therefore, the development of a new aminooxygenation reaction is still highly attractive [4]. Most of the existing aminooxygenation reactions involve an intramolecular cyclization step [5][6][7][8][9][10][11][12][13

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• used extensively in polymer chemistry because of the ability of alkyl radicals to participate in chain reactions [2][3][4]. They have also been used extensively in small molecule synthesis, particularly in an intramolecular cyclization setting [5][6][7][8][9]. However, while the ability of alkyl

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• intramolecular cyclization. Finally, 10 is oxidized to give pyrazolo[3,4-d]pyrimidine 5. Another route is that 7 undergoes an intramolecular Pinner reaction to form 11. Then 11 rearranges to dihydropyrazolo[3,4-d]pyrimidin-4-ones 13 via Dimroth rearrangement and 13 is oxidized to provide 14 [49]. Finally, 14

A new approach to ferrocene derived alkenes via copper-catalyzed olefination

• Vasily M. Muzalevskiy,
• Aleksei V. Shastin,
• Alexandra D. Demidovich,
• Namiq G. Shikhaliev,
• Abel M. Magerramov,
• Victor N. Khrustalev,
• Rustem D. Rakhimov,
• Sergey Z. Vatsadze and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2015, 11, 2072–2078, doi:10.3762/bjoc.11.223

• we assume that the radical-ions formed after the first electron transfer would enter the intramolecular cyclization reaction involving the second adjacent double bond with subsequent electropolymerization. The latter is confirmed by a pronounced decrease in current values (3–4 times) as compared to

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• of aldehyde to form a second aldimine. Finally, 6-endo-enol-endo intramolecular cyclization leads to piperidone formation (Scheme 2) [58][59]. Structural and conformational analysis of piperidones 1–8 by NMR and X-ray diffraction Solution characterization of 1–8 was performed by 1H and 13C NMR, and

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• by intramolecular trans-esterification from 6, 7 and 8, as well as cyclic amines by intramolecular cyclization involving primary amine resulting from hydrogenation of the nitrile functionality in 5. All these aspects will be further developed in our group. Cross metathesis of 1 with methyl acrylate

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• addition of the selenium reagent on a double bond of the starting 5-alkenylhydantoin prior the cyclization. These intermediates are readily converted into the more stable cyclic seleniranium cations. A key step of the mechanism is an intramolecular cyclization which is realized through an anti-attack of

• Figure 4). These intermediates are actually the reactant complexes for intramolecular cyclization. The fourth step of the proposed mechanism is a ring forming reaction which is achieved through an anti-attack of the internal nucleophile, amidic nitrogen N(1) at carbon C(5) or C(6) yielding the five

• is favored. These intermediates are readily converted into the more stable cyclic seleniranium cations. The key step is a selenium-induced intramolecular cyclization which is accomplished through an anti-attack of the internal nucleophile, amidic nitrogen, to the seleniranium cation yielding the

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• configuration) and 6i in 16:31:28:25 GC–MS ratio. The presence of these products can be explained only by the formation of the substituted SF5-phenyl radical which undergoes borylation to 2i, hydrogen atom transfer followed by borylation to 2i’, intramolecular cyclization to 5i or hydrogen abstraction to 6i

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

• bearing two different olefin units one being an α,β-unsaturated moiety, the tandem CM–IMDAR protocol would initiate on the electronically neutral olefin. Furthermore, those dienes could undergo an intramolecular cyclization (RCM) promoted by the ruthenium carbene that would compete with the desired

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

• alkenyl chain of sufficient length the [n]paracyclophane 172 was obtained by an intramolecular cyclization (Scheme 27). Alcaide and co-workers [153] have reported the synthesis of different bis(dihydrofuryl)cyclophane scaffolds 179 from carbonyl compounds. 1,4-Bis(3-bromoprop-1-ynyl)benzene (175) was

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• molybdenum(VI)-catalyzed etherification of allylic alcohol with a gold(I)-catalyzed intramolecular cyclization process [5][6]. During the optimization process of this synthesis, we examined several catalysts to transform allylic alcohol 1 into ether 2, including Re2O7, which is described to efficiently

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• . reported the base-catalyzed intramolecular cyclization of alkynyl alcohols at high temperatures to give 1,4-oxaza heterocycles [32]. In this manuscript we envisaged a synthetic strategy leading to the core skeleton of marine products 6 and 7 (Figure 2) or their analogues with short reaction times and an

• atom-economic process using a gold-catalyzed alkyne cyclization reaction as the key step. Pyrrole and indole, bearing one (substituted) propargyl and carboxy group was initially designed as model substrate for the construction of 6 and 7. Gold-catalyzed intramolecular cyclization of enyene carboxylic

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• intramolecular cyclization of a chiral alkenylated pyrrolidinone, followed by hydroxylation [32], or by the intramolecular ring closure of chiral pyrrolidine diesters followed by ester and oxo group reduction [33], while the syntheses of (+)-epitashiromine starts from a chiral morpholine derivative, with nitrone

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• reorient itself to place the remaining OH function close to the remaining NCO moiety. The subsequent intermolecular pathway is much more likely than the intramolecular cyclization to 29. Conclusion Having developed different, mostly high-yielding routes to various diamino[2.2]paracyclophanes and related

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• cyclization reaction, and the expected products 9A–L were obtained in good to excellent yields (80–93%, Table 3, entries 1–12). Based on the results of the present studies, we propose a plausible mechanism for the transformation. As depicted in Scheme 2, the intramolecular cyclization is initiated by the

• ]quinazolin-9(1H)-ones 9A–L could be generated by the treatment of substituted 2-(3-butynyl)-4(3H)-quinazolinones 8A–L with AgOTf under the optimized reaction conditions. As illustrated in Table 3, 2-(3-butynyl)-4(3H)-quinazolinones 8A–L with different substituents were well-tolerated in this intramolecular

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322