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

• synthetic strategy, a solution-phase parallel synthesis of 1,2-dihydroisoquinolines has been developed by Larock, providing a 105-membered library for biological assays [58]. Moreover, an extension to γ-ketoalkyne encompassed in diverse heterocyclic frameworks (quinoline, pyridine or benzo[b]thiophene) has

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• allows their application in the synthesis of important heterocycles such as indole [28], dihydropyridine [29], quinoline [30], pyrrole [31] and pyridinone [32]. Furthermore, they can take part in one-pot multicomponent reactions with both nucleophilic and electrophilic reactants, leading to a fast access

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• and quinoline derivatives, and nitro alcohols. Thus, part of the human life and life style is dependent of nitration as a unit reaction. In general, several types of nitrating agents are used for nitration. A literature search covering the last 50 years is presented in Figure 1. One third reports on

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• been reported by numerous authors. Among them, Zhao et al. [18] studied the coupling of non-activated aryl iodides with different alkenes using Pd-MCM-41-NH2. Other examples include Pd-FSM 16 (functionalised with pyridine-carboimine or quinoline-carboimine) [19], oxime carbapalladacycle anchored on

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• coupling constants (J) are given in Hz. Elemental analyses were determined using a Thermo Finnigan Flash EA 1112 instrument. 6-Chloro-[1,2,5]selenadiazolo[3,4-h]quinoline (2). A mixture of selenadiazolo[3,4-h]quinolone 1 (5.0 g, 20.0 mmol) and POCl3 (10 mL, 16.4 g, 0.1 mol) was stirred at 90 °C for 15 min

• alkalisation of hydrochloride 5. [1,2,5]Selenadiazolo[3,4-h]quinoline (6). SeO2 (58.6 mg, 0.53 mmol) dissolved in water (1 mL) was added to a stirred solution of hydrochloride 5 (100 mg, 0.51 mmol) in water (1 mL) and stirring was continued for an additional 15 min at room temperature. Next, the reaction

• , 23.17. 9-Chloro-[1,2,5]selenadiazolo[3,4-f]quinoline (10). A mixture of selenadiazolo[3,4-f]quinolone 9 (2.0 g, 8.0 mmol) and POCl3 (4 mL, 6.56 g, 42.8 mmol) was stirred at 90 °C for 3 h. After the reaction was complete, the mixture was cooled to 0 °C in an ice bath followed by the addition of crushed

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

• ] and neatly introduces the required chloride substituent at the 5-position. While isolated pyridines are a vital component in numerous drugs the related quinoline/quinolone scaffolds are becoming increasingly common. One such example is nalidixic acid (1.101, in fact a naphthyridone, Figure 2

Gold-catalyzed regioselective oxidation of propargylic carboxylates: a reliable access to α-carboxy-α,β-unsaturated ketones/aldehydes

• Kegong Ji,
• Jonathan Nelson and
• Liming Zhang

Beilstein J. Org. Chem. 2013, 9, 1925–1930, doi:10.3762/bjoc.9.227

• carboxylate; Introduction We reported in 2010 [1] that α-oxo gold carbenes could be conveniently generated as reactive intermediates in gold-catalyzed intermolecular oxidation of alkynes. By using pyridine N-oxides [1] and later 8-substituted quinoline N-oxides [2] as the external oxidants, this approach

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• class of compounds is characterized by a quinolone or quinoline nucleus substituted in position 3 or 4 by a farnesyl chain. In addition, aurachins can further be functionalized by biosynthetic oxidative processes [2][3][4][5]. Since then, additional members of this natural product family were discovered

• nonselectively oxidized products. The crude product 21a was then submitted to benzyl group hydrogenolysis. As expected upon completion of the reaction, the 4,5-dihydrofuro[3,2-c]quinoline N-oxide ring system 22 was obtained as a racemic pair of diastereoisomers in a 1:1 ratio, supposedly formed through the

• epoxidation conditions, i.e., the 4,5-dihydrofuro[2,3-c]quinoline N-oxide, and thus to synthesize chain analogues of 6. Biological investigations demonstrated the superiority of the natural product 4 regarding its inhibitory effect on Gram-positive bacteria, human cancer cell lines, and above all on the

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• (9) and diphenyl-1,3,4-oxadiazole (10); and thioflavin-T analogues such as benzothiazole (11), benzoxazole (12), benzofuran (13), imidazopyridine (14), and benzimidazole (15); as well as quinoline (16) and naphthalene (17) derivatives (Figure 1B). In this review, we provide an overview of these AD

• /g at 60 min). In vitro labeling of Aβ plaques in AD brain sections showed a strong signal with low background, and in vivo plaque labeling in transgenic mice was also successful. However, this scaffold is lacking in detailed SAR analysis compared to the imidazopyridine scaffold. Quinoline and

• naphthalene analogues Quinolines Investigation of the quinoline scaffold for imaging in AD has yielded some interesting results, despite there only being a few examples in the literature. The [18F]-labeled 2-fluoroquinolin-8-ol [18F]CABS13 (149) has recently been reported (Figure 5) [98]. The straightforward

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• ketone 5d upon reduction with SnCl2 cyclized to pyrrolo[3,2-f]quinoline-9-carbonitrile 7 [17]. The removal of the benzyloxymethyl group from 1-(benzyloxymethyl)pyrrolo[3,2-e]indoles by catalytic hydrogenation has been described by Macor [6]. The hydroxy group from the N-hydroxypyrrole fragment can be

3-Pyridylnitrene, 2- and 4-pyrimidinylcarbenes, 3-quinolylnitrenes, and 4-quinazolinylcarbenes. Interconversion, ring expansion to diazacycloheptatetraenes, ring opening to nitrile ylides, and ring contraction to cyanopyrroles and cyanoindoles

• Curt Wentrup,
• Nguyen Mong Lan,
• Adelheid Lukosch,
• Pawel Bednarek and
• David Kvaskoff

Beilstein J. Org. Chem. 2013, 9, 743–753, doi:10.3762/bjoc.9.84

• -quinoline (44): The azide was sublimed at 80 °C and deposited with Ar at 22 K to form a matrix. Principal absorptions of the azide at 11 K: 2100, 1590, 1420, 1340, 1270, 1100 cm−1. Irradiation of the azide 44 at 308 nm or at 310–390 nm for 30 s afforded the nitrile ylide 47 together with a smaller amount of

• ascribed to 46 and reformation of the IR and UV–vis bands ascribed to the nitrile ylide 47. It was possible to cycle several times between these two species by using λ > 550 nm and λ = 310–390 nm, respectively (Figure 2 and Figure 3). FVT of 3-azido-2-phenyl-3-quinoline (44): (a) A sample of the azide (0.2

• g, 0.8 mmol) was sublimed at 60–80 °C and pyrolysed at 500 °C/10−4 mbar in the course of 3 h. The products were separated by flash chromatography on silica gel, eluting with chloroform. Indolo[3,2-b]quinoline (50) was obtained in 56–65% yield in different experiments: mp 250–251 °C (lit. [43] 248 °C

Synthesis of SF₅-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes

• Petr Beier and
• Tereza Pastýříková

Beilstein J. Org. Chem. 2013, 9, 411–416, doi:10.3762/bjoc.9.43

• observed compared to unsubstituted ortho-aminoacetophenone, but it could be overcome by using an excess of the condensation reagent and longer reaction times. Quinoline 12 was prepared in high yield by the Friedländer annulation reaction of 10a with excess ethyl acetoacetate in the presence of catalytic

• CAN using modified literature conditions (Scheme 3) [32]. Similarly, aminoketone 11a was condensed in good yield with cyclohexanone to provide quinoline 13 in good yield (Scheme 4). Finally, quinazoline 14 was synthesized by the reaction of aminoketone 11a with benzylamine in the presence of t-BuOOH

• Wipf and co-workers [29][30]. Synthesis of quinoline 12. Synthesis of quinoline 13. Synthesis of quinazoline 14. Synthesis of SF5-containing benzisoxazoles 7–9. Synthesis of ortho-aminobenzophenones 10 and 11. Supporting Information Supporting Information File 84: Experimental details

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• three-component reaction of arylamine, isatin and cyclopentane-1,3-dione. Results and Discussion Recently we found that the four-component reactions of arylamine, acetylenedicarboxylate, isatin and dimedone in acetic acid resulted in the novel functionalized tetrahydrospiro[indoline-3,2’-quinoline

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• Wentao Gao Guihai Lin Yang Li Xiyue Tao Rui Liu Lianjie Sun Institute of Superfine Chemicals, Bohai University, Jinzhou 121000, China 10.3762/bjoc.8.213 Abstract An efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives 4a–l

• three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields. Keywords: Eaton’s reagent; Friedel–Crafts acylation; Friedländer reaction; one-pot; PPA; quinoline; tetracyclic-fused; Introduction Polycyclic

• heterocycle-fused quinoline systems as important group compounds can be found in many biologically active natural products as well as in pharmacologically significant molecules, and have wide applications in medicinal chemistry [1][2][3][4]. It has been well-established that planar heterocycle-fused tri- or

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• Quinoline aldehydes are important synthetic intermediates in the synthesis of heterocyclic compounds that are used in the manufacturing of dyes [1] and pharmaceuticals [2][3]. 3-Substituted and 2,3-di-substituted quinoline-4-carbaldehyde derivatives are used in the synthesis of immunosuppressant KF20444 [4

• ] and 5-HT3 receptor antagonists [5]. Quinoline mevalonolactones, prepared from 3-methylquinoline-4-carbaldehyde, act as inhibitors of HMG-CoA reductase [6]. 3-Substituted quinoline-4-carbaldehyde derivatives are used in the development of molecular probes for the identification of extra interaction

• methods for the preparation of quinoline-4-carbaldehyde [12][13][14][15][16][17][18][19][20][21][22][23][24], only a few methods [6][9] are available for the preparation of 3-methylquinoline-4-carbaldehyde derivatives. In connection with the synthesis of camptothecin, we needed a general, high-yielding

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• reaction as the key step, reaction of aldehyde 56 with α,β-unsaturated aldehyde 57, catalyzed by chiral prolinol ethers Ie/HOAc in acetonitrile, provided quinoline derivative 58 with high yield and with high enantioselectivity (Scheme 29). In contrary to the work of Li, the presence of 4Å MS had a negative

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• the nucleophile to the tertiary amino group between the side chains of the catalysts. The re-face of the Michael acceptor is shielded by the flat quinoline unit and the si-attack of the malonate is preferred, affording R-selectivity (Figure 3). Determination of the absolute configuration The absolute

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

• ], isolated from roots of the West African plant Cryptolepis sanguinolenta [7]. Cryptotackieine, a member of the indolo[2,3-b]quinoline class of heterocycles [8], has been shown to be a strong inhibitor of Plasmodium falciparum growth [9]. 2-Amino-α-carbolines have also been identified as mutagens produced in

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• benzofuroyl-based compounds [39][40][41][42][43]. We have recently reported the synthesis of quinolyl-substituted carbazoles [44] and benzofuranyl-substituted quinoline [45]. Thus, in light of the above findings and in the context of our ongoing work on the synthesis of new heterocyclic compounds, we found it

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• -group are able to direct the zincation. Thus, the diiodoquinoline 22 is regioselectively zincated (25 °C, 12 h) to intermediate 23 leading to the polyfunctional quinoline 24 in 78% yield after copper(I)-mediated acylation (Scheme 4 and Supporting Information File 1, Procedure 1) [8]. This

• exchange reaction for the regioselective functionalization of quinolines. Thus, the 2,3-dibromoquinoline (65) is regioselectively converted to the 3-magnesiated quinoline derivative 66. Using the same exchange reagent, iPrMgCl·LiCl (64) and 2,4-dibromoquinoline (68), it is now possible to obtain the 4

• -magnesiated quinoline 69. All these magnesiations proceed at low temperature (−50 °C to −78 °C) and are complete within 2 h reaction time. After reaction with TsCN, the corresponding nitriles 67 and 70 were obtained in 84–85% yield (Scheme 12 and Supporting Information File 1, Procedure 5) [36]. The rate of

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• tetrahydroquinolines obtained through the Povarov multicomponent reaction have been oxidized to the corresponding quinoline, giving access to a single product through a two-step sequence. Several oxidizing agents were studied and manganese dioxide proved to be the reagent of choice, affording higher yields, cleaner

• reactions and practical protocols. Keywords: manganese dioxide; multicomponent reactions; oxidation; Povarov; quinolines; tetrahydroquinolines; Introduction Heterocycles are ubiquitous scaffolds in pharmaceuticals, natural products and biologically active compounds. Quinoline systems in particular

• , Thompson et al. described the oxidation of fused pyrrolohydroquinolines (type 6) using MnO2 obtained from batteries. A kinetic competition between two processes was observed, and the desired double oxidation to the corresponding fused quinoline 7 took place, along with the oxidation–elimination sequence

Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

• Yingdong Luo,
• Guozhu Zhang,
• Erik S. Hwang,
• Thomas A. Wilcoxon and
• Liming Zhang

Beilstein J. Org. Chem. 2011, 7, 596–600, doi:10.3762/bjoc.7.69

• ][13][14][15][16][17] or via allenes generated in situ [18][19][20][21]. We have recently shown that highly reactive gold carbenes can be generated from alkynes via gold-promoted intermolecular oxidation by pyridine/quinoline N-oxides [22][23][24][25], making benign alkynes effective surrogates of

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• Wentao Gao Jia Liu Yun Jiang Yang Li Institute of Superfine Chemicals, Bohai University, Jinzhou 121000, China 10.3762/bjoc.7.28 Abstract A facile and inexpensive synthesis of a series of novel methylenedioxy-bearing 2-(benzofuran-2-yl)-quinoline-3-carboxylic acid derivatives 3a–h via the one-pot

• ; methylenedioxy-bearing; one-pot; quinoline-3-carboxylic acid; salicylaldehyde; Introduction Heterocyclic systems containing a quinoline nucleus are an important group of compounds in medicinal chemistry, and are ubiquitous sub-structures associated with biologically active natural products [1][2][3][4]. Some

• quinoline compounds especially those containing heterocyclic systems at 2-position have been shown to display a wide spectrum of biological activities such as cytotoxic, anti-inflammatory and antifungal behavior [5][6]. For example, 2-(furan-2-yl)quinoline-4-carboxylic acid (and analogues) (1, Figure 1) was

Synthesis of 3-(quinolin-2-yl)- and 3,6-bis(quinolin-2-yl)-9H-carbazoles

• Yang Li and
• Wentao Gao

Beilstein J. Org. Chem. 2010, 6, 966–972, doi:10.3762/bjoc.6.108

• : acetylcarbazole; β-aminoaldehyde; β-aminoketone; Friedländer condensation; sodium ethoxide; Introduction Nitrogen-containing heterocycles are a very important group of organic compounds because of their wide application in medicine, agriculture, and technology. Among these, quinoline and carbazole derivatives

• are of significant synthetic interest due to their diverse range of biological activities. Compounds containing a quinoline framework have been found applications as pharmaceuticals and agrochemicals, as well as being general synthetic building blocks [1][2][3]. Industrial, biological, and synthetic

• significance places this scaffold in a prestigious position. Studies on new quinoline derivatives appear frequently in the chemical literature. Therefore, significant effort continues to be directed toward the development of new quinolines . In particular, there is much current interest in the quinoline ring