Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• with pyridines. In 2011, Maruoka and co-workers investigated the use of isoquinolinium ions protected as azomethine imines [30]. The use of a CuOAc/Ph-Pybox catalyst enables the addition of a wide variety of alkynes to form isoquinolines with tertiary stereocenters in high yields and ee’s (Scheme 8A

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• preventing the catalyst deactivation. In 2013, Moss generalized the method to the formation of azepines fused with a variety of heteroaromatics including pyrimidines, pyridines, thiazoles and pyrrazoles [59]. Interestingly, most of the heteroaryls possess a chlorine substituent but no explanation was given

• ). Various substituents on the pyridyl ring such as halides, trifluoromethyl or triflate groups were found to be suitable basicity modulators and the alkenes containing the corresponding disubstituted pyridines were efficiently coupled to methyl acrylate by utilizing a CM reaction. In addition, steric

• moieties such as pyridines, pyrimidines, imidazoles and pyrazoles (Scheme 37). From the selected examples discussed above, we tried to delineate some trends regarding to the use of alkenes possessing N-heteroaromatics in RCM and CM. In RCM, GI and GII are usually preferred and diluted conditions are

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• , which allowed the synthesis of various 2-(o-haloaryl)pyridines with improved selectivity towards mono-halogenation in the presence of a copper catalyst [35]. As outlined in Scheme 4, the presence of molecular oxygen as the alternative oxidant enabled most entries providing monohalogenated products with

• (Scheme 18). Rather recently, Liu and co-workers [62] reported an alternative approach to the synthesis of 3-brominated indolizines via copper-catalyzed three-component cascade reactions of pyridines 56, α-bromoketones 57 and maleic anhydride (58). The construction of the products involved in the three

• strategy, Wang and co-workers [63] developed an efficient method for the halogenation of azacalix[1]arene[3]pyridines 62 for the synthesis of halogenated products 63. The synthesis of the products was mediated by the formation of Cu(III) complex 64, as observed in the previous study [64], via the assembly

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• -unsaturated nitrones, which undergo a subsequent thermal rearrangement to the corresponding tri- and tetrasubstituted pyridines. The optimization and scope of these transformations is discussed. Initial mechanistic experiments suggest a reaction pathway involving oxygen transfer followed by cyclization

• tetrahydroquinolines such as 5 (Scheme 1A). These studies encouraged us to consider if similar N-alkenylnitrones 8 could be accessed by a Chan–Lam coupling and transformed into the corresponding substituted pyridines 9 (Scheme 1B). Pyridines are important heterocycles that are often found in biologically active

• molecules [14][15][16][17][18][19][20][21]. Due to the high demand for these compounds, there are many methods for preparing substituted pyridines through condensation reactions [22][23][24][25][26], cycloadditions [27][28][29][30], functionalization of parent pyridine structures [31][32][33][34][35][36][37

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

• 3b was very fast and a vigorous evolution of nitrogen was observed affording the borylated product in a moderate yield together with a mixture of SF5-pyridines in ca. 10% GC–MS yield (Table 2, entry 7). Finally, the use of a 4-fold excess of pyridine in acetonitrile was found to be optimal

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• small collection of 22 imidazo[1,2-a]pyridines 136 was prepared within four working days. The synthetic route consisted of an aldol condensation between various acetophenones 137 and ethyl glyoxylate (138). This was followed by an HBF4-catalysed cyclocondensation of the resulting Michael acceptor 139

• compound library contained zolpidem (142) and alpidem (143) (Figure 5), two FDA approved drugs for which affinity data were already literature reported the authors were able to validate their method by matching their affinity data. Using this setup, solutions of the remaining imidazo[1,4-a]pyridines (600

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• partially due to the fact that the π–π-stacking of pyridines [50] was a competing interaction. The most probable rupture force, used in the KBE model, was due to the coordination complexes. Methods using the whole data set are strongly influenced by the stacking interaction and would have needed heavily

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• -(polyfluoroalkyl)propionates with 3-amino-5-hydroxypyrazole allowed to obtain not only dihydropyrazolo[1,5-a]pyrimidines but also pyrazolo[3,4-b]pyridines due to the peculiarities of the binucleophile used [12]. To the best of our knowledge, there is no published data about the interaction of 2-ethoxymethylidene-3

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• cyanoacetate) with triethylamine as base catalyst afforded functionalized 1-benzamidospiro[indoline-3,4'-pyridines] in good yields. 1H NMR spectra indicated that an equilibrium of cis/trans-conformations exist in the obtained products. Keywords: acetylenedicarboxylate; benzohydrazide; 1,4-dihydropyridine

• ], we herein wish to report the efficient synthesis of functionalized 1-benzamidospiro[indoline-3,4’-pyridines] via one-pot four-component reactions of benzohydrazide, acetylenedicarboxylate, isatin and malononitrile. Results and Discussion According to the reaction conditions of the previously reported

• triethylamine as the base catalyst were introduced into reaction system. The subsequent reaction proceeded very smoothly at room temperature to give the 1'-benzamidospiro[indoline-3,4’-pyridines] 1a–d in satisfactory yields (Table 1, entries 1–4). It is known that hydrazine reacts firstly with

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -aminoazoles, including thiazole [13][14] and 1,3,4-thiadiazole [15][16] derivatives, or 2-aminoazine-based heterocycles, such as pyridines [17][18][19], pyrimidines [20][21][22][23][24] and pyrazines [25][26][27], have recently been utilized as Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• Pharmacy, University of Siena, I-53100, Siena, Italy Institute of Synthetic Chemistry, Kaunas University of Technology, LT-50254 Kaunas, Lithuania 10.3762/bjoc.10.183 Abstract A straightforward synthesis of 6-substituted 1-phenyl-3-trifluoromethyl-1H-pyrazolo[4,3-c]pyridines and the corresponding 5-oxides

• the field of pyrazoles, pyridines and condensed systems thereof trifluoromethyl-substituted congeners can be found as partial structures in several pharmacologically active compounds. In the pyridine series the HIV protease inhibitor Tipranavir (Aptivus®) [6] may serve as an example, within the

• -substituted pyrazolo[4,3-c]pyridines. The latter heterocyclic system represents the core of several biologically active compounds, acting, for instance, as SSAO inhibitors [10], or inhibitors of different kinases (LRRK2 [11][12], TYK2 [13], JAK [14][15]). Results and Discussion Chemistry The construction of

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• aqueous phase. In our study the volatile bouquet of the actinomycete Streptomyces sp. FORM5 was investigated and several new 2-alkylated pyridines were identified using the closed-loop stripping analysis (CLSA) [7] headspace technique followed by GC–MS analysis and synthesis of the target compounds for

• to the natural compound, now called streptopyridine E. The mass spectra of 2-(pent-1-enyl)pyridine and 2-(pent-2-enyl)pyridine, compounds synthesized for comparison, are shown in Supporting Information File 1 and differ from that of 8. Finally, pyridines 6 and 7 were synthesized also by Fürstner

• propylpyridine (6). In the bouquet of the headspace extract of Streptomyces strain FORM5 several other compounds besides the pyridines 6–12 were identified (Figure 7, Table 1). The most abundant of these were dimethyl disulfide (35), accompanied by other sulfur components as dimethyl trisulfide (36), dimethyl

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• were prepared starting from commercially available 4-amino-2-chloropyridine (4) and 2-amino-6-bromopyridine (5), respectively. After protection of the amino functions as 2,5-dimethylpyrroles, pyridines 6 and 7 were transformed into the corresponding 2,2’-bipyridines 8 and 9 via a nickel-catalysed homo

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• , University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland 10.3762/bjoc.10.40 Abstract Two new 9,9’-spirobifluorene-based bis(4-pyridines) were synthesised in enantiopure and one also in racemic form. These ligands act as concave templates and form metallosupramolecular [(dppp)2M2L2] rhombi with cis

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• . Keywords: alkoxyallenes; condensations; DFT calculations; β-ketoenamides; multi-component reactions; olefin metathesis; pyridines; pyrimidines; Introduction Multicomponent reactions (MCRs) generally allow a diversity-oriented fast and efficient access to complex synthetic intermediates and are thus

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

• ][21]. However, these methods cannot give access to various polysubstituted 1,8-naphthyridin-2-ones. Recently, we reported an efficient method for the synthesis of polysubstituted 2,3-dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano[2,3-b]pyridines from 1,2,4-triazines via an inverse electron

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• syntheses of otherwise non-readily obtainable pyrans [1][2][3], pyridines [3][4][5] and polysubstituted aromatics [6][7]. The synthesis of 2-amino-4H-pyrans by these reactions has recently been surveyed. Since the first report describing the preparation of 2-amino-4H-pyrans by the addition of active

• methylenenitriles to α,β-unsaturated ketones [8], 2-amino-4H-pyrans 1 (Scheme 1) have become the central focus of a number of chemical and biological investigations [9][10]. Perez et al. recently reported an interesting method for the synthesis of condensed pyridines 2 through a three-component reaction of

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

• chloro-substituted pyridines and related heterocycles, from which the triazolopyridines and other related fused heterocycles can be obtained after oxidative cyclization [14]. In accordance with the significance shown by triazolopyrimidines, the development of complementary and simple synthetic methods

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

• other value added structures that contain complex pyridines. The route terminates in a batch crystallization yielding high purity CAPIC. This outcome is expected to facilitate regulatory implementation of the overall process. Keywords: continuous; flow chemistry; HIV; Knoevenagel; nevirapine

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• [114] as well as of various arenes and heteroarenes (pyridines, pyrimidines, pyrazines, quinolines, pyrroles, thiophenes, furans, pyrazoles, imidazoles, thiazoles, oxazoles, thiadiazoles, triazoles) [115]. The yields were low to excellent, depending on the substrate (Scheme 12 and Figure 20). Iron(II

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

• -membered heterocyclic rings in pharmaceutical actives inevitably generates a substantial body of reference material. Consequently this review has been broadly partitioned into six consecutive sections categorised by analogous groupings of heterocyclic rings. The subsections are: Pyridines and quinolines

• . Review 1. Pyridines and quinolines The pyridine ring can be considered as one of the simplest yet most important heteroaromatic structures. Naturally occurring in many important compounds such as the vitamins niacin and pyridoxine, the ubiquitous redox system NADP/NADPH and a number of alkaloids

• including nicotine, pyridine, is thus important for a wide range of biological activities [8]. Consequently, the pyridine ring is utilised in many pharmaceutical actives and possibly even more commonly found in agrochemical products. This can be rationalised by the fact that simple pyridines readily undergo

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

• Adrián Gómez-Suárez,
• David J. Nelson,
• David G. Thompson,
• David B. Cordes,
• Duncan Graham,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2013, 9, 2216–2223, doi:10.3762/bjoc.9.260

• ) with each (hetero)aromatic amine in THF at room temperature for 20 h. A range of aromatic amines were employed, including aniline, diphenylamine, pyridines, a pyrimidine and one isoquinoline. The corresponding complexes were obtained in analytically pure form and in good yields as yellow or white

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• synthetic transformations (Scheme 1), including Bohlmann–Rahtz cyclodehydration of aminodienones 1 to the corresponding pyridines 2 [44][45], Fischer indole synthesis of tetrahydrocarbazole 5 from phenylhydrazine (3) and cyclohexanone (4) [44], and hydrolysis of 4-chloromethylthiazole (6) to give the

• that this cyclocondensation proceeds in a similar fashion and high efficiency under microwave irradiation [48], and that we have previously demonstrated that pyridines and pyrimidines can both be formed rapidly and efficiently from ethynyl ketones using microwave dielectric heating, the transfer of

• synthetic procedures to a continuous flow processing regime in a microwave flow reactor seemed highly feasible to access pyridine derivatives in a single step. Results and Discussion Synthesis of pyridines in a continuous flow reactor Many of our previous studies on the synthesis of pyridines in a

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• different substituents in positions 1, 2, 3 and 4 were prepared by alkylation of the parental commercially available pyridines (see Supporting Information File 1, Table S1). The results of this cyclization reaction (Scheme 2) are summarized in Figure 1. Generally the reaction was complete in 24 hours and

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• -dihydrofurans, polysubstituted pyridines, pyrido[1,2-a]benzimidazoles and charge-separated zwitterionic salts [26][27][28][29][30][31]. We envisaged that in situ generated pyridinium ylide might react with the reactive carbonyl group of isatins to afford spiro epoxyoxindoles (Scheme 1). To test this feasibility