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

• superelectrophilic activation of the N-formyl group by TfOH in the reaction with benzene resulted in the formation of N-(diphenylmethyl)-substituted dihydroquinolinones. Keywords: alkynes; quinolinones; Friedel–Crafts reactions; superacids; superelectrophilic activation; Introduction Quinoline derivatives are a

• very important class of heterocycles, which are used in chemistry, biology, medicine, and materials science. For instance, see a series of recent reviews on anti-malaria drugs containing a quinoline motif in the structure [1][2][3]. The synthesis of quinolines is an important task of organic chemistry

• ][12][13][14], we continued to develop some methods for the syntheses of quinoline derivatives. Previously we showed, just in a few examples, that some 3-aryl-N-(aryl)propiolamides reacted with benzene under the action of Brønsted or Lewis superacids affording 4-aryl-4-phenyl-3,4-dihydroquinolin-2(1H

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• with the phenyl and 2-naphthylthiazolones, respectively (Scheme 12, compound 70 versus 71 and 72 versus 73). On this basis, the authors propose a bifunctional way of action of the catalyst, wherein the pyridine/quinoline nitrogen could coordinate to one of the free N–H hydrogen atoms of the catalyst. α

A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin

• Matthias Bender,
• Henrik Mouritsen and
• Jens Christoffers

Beilstein J. Org. Chem. 2016, 12, 912–917, doi:10.3762/bjoc.12.89

• [M + H+]. 1-Deoxy-1-(8-hydroxy-2,4-dioxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinoline-10-yl)-D-ribitol (1) A mixture of aldehyde 13 (90 mg, 0.57 mmol), aminouracil 12 (150 mg, 0.57 mmol), NEt3 (0.10 mL, 0.68 mmol) and EtOH (3 mL) was heated in a closed reaction vial at 150 °C for 3 h. After cooling to

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• state TS3 was proposed. Herein, the NH from the thioamide and the protonated quinoline moiety would activate and fix the nitroalkene framework through hydrogen-bonding interactions. Simultaneously, the oxygen atom of the hydroxy group would orientate the attack of the indole by the Si face through the

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• 9, 19 and 22). Considering the low basicity of compound 3i, 3 equivalents of the stronger acid TFA were used (Table 2, entry 25). Next, the effect of benzoannulation (quinoline) and C–H for N substitution (diazines) in the pyridine ring was studied. Scheme 1 provides an overview of the results for

• the World Health Organization essential medicines list and despite numerous side effects it remains one of the most effective antimalarial drugs on the market [37][38]. Its classical synthesis (Scheme 2, top) is based on the lithiation of 4-bromo-2,8-bis(trifluoromethyl)quinoline (7a) and quenching

• with CO2 resulting in the formation of 2,8-bis(trifluoromethyl)quinoline-4-carboxylic acid (8). Reaction of 8 with in situ generated 2-pyridyllithium (9) finally yields ketone 10 [39]. We considered a new approach based on 4-(pyridin-2-ylmethyl)-2,8-bis(trifluoromethyl)quinoline (12) as the substrate

Solving the puzzling competition of the thermal C²–C⁶ vs Myers–Saito cyclization of enyne-carbodiimides

• Anup Rana,
• Mehmet Emin Cinar,
• Debabrata Samanta and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 43–49, doi:10.3762/bjoc.12.6

• , M+ − CH3), 246 (47), 245 (100, M+ − N(CH3)2), 244 (20), 243 (26), 231 (14), 218 (15), 203 (18), 183 (62); ESIMS: calcd. for (C19H20N3)+, 290.2; found, 290.2. 3,7-Dimethyl-1-phenyl-1,2,3,4-tetrahydropyrimido[4,5-b]quinoline (12). To 10 mL of dry degassed toluene was added 2-(3-(dimethylamino)prop-1

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

• observed lower ee’s with Pybox and Box ligands, and only 49% ee with Quinap. However, investigation of novel Pinap ligands led to notably higher ee’s (Scheme 7) [29]. These reaction conditions enable alkynylation of quinoline (20), isoquinoline (21), and pyridine (22) substrates, albeit in lower yields

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

• it may be suspected that the presence of the two chlorine atoms significantly decreased the basicity of the pyridine (Scheme 21). Tricyclic compound 59 was prepared by a RCM of diene 58 that incorporates a quinoline moiety [61]. In this case, a phenyl group was present at C2 and may be responsible

• catalyst caused by the quinoline (Table 4, entry 4). In their retrosynthesis of haminol A, O’Neil et al. initially envisionned to access the trienic compound using a cross-metathesis/benzoyloxysulfone elimination sequence. The CM would involve 3-vinylpyridine 70 as one of the two partners (Scheme 27) [75

• , biologically relevant conditions were selected (rt, t-BuOH/H2O) and CM involving allyl sulfides that contain functional groups commonly found in DNA-intercalators and N-heteroaromatics were investigated. When a quinoline was present on the allylic sulfide, allylic alcohol was found to be the unique suitable

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• undertake the amidation to provide indolinone product 28''. An important factor enabling the C–H bond transformation was the presence of the quinoline auxiliary which acted as a bidentate fragment to incorporate the copper catalyst and facilitate the bond cleavage and formation via intermediates A and B

• products 49 or 50 by incorporating phthalimide/saccharin 46. Under the standard conditions, however, the reaction of benzamide with 2-phenylpyridine provided product 51 with low yield (Scheme 14). As a special aromatic system, quinoline N-oxides were well investigated in their reactivity for metal

• -catalyzed C–H activation. Based on the known results of quinoline N-oxide C–H alkenylation [61], arylation [62] and alkylation [63] etc, Li and co-workers [64] investigated and established the C–H amidation of quinoline N-oxides 52 via copper catalysis. According their results, quinoline N-oxides 51

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

• copper-catalyzed arene C–H methoxylation using the generally applicable quinolin-8-yl [40] as DG, Stahl et al. [41] discovered that using a CuCl/LiCl/O2/AcOH catalytic system resulted in the formation of C-5 chlorinated quinoline, demonstrating the pivotal role of the DG in inducing the reaction pathway

• ). Control experiments in the presence of TEMPO suggested that the reaction might proceed via a C-centered free radical provided by SET between the quinoline substrate and the cupric salt. In recent years, the formation of C–F chemical bonds received global research interest owing to the particular functions

• using LiCl. Copper-catalyzed C–H halogenation of 2-arylpyridines using LiX. Copper-mediated selective C–H halogenations of 2-arylpyridine. Copper-catalyzed C–H o-halogenation using removable DG. Copper-catalyzed C–H halogenations using PIP as DG. Copper-catalyzed quinoline C–H chlorination. Copper

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• predicted, most densely packed lattice for a C5-symmetric macrocycle [49]. Jiang and co-workers also prepared fluorine-containing quinoline oligoamides, which they found self-assembled into unique double and quadruple helices [52][53]. The fluorine atoms in the oligomers induced the backbone to fold by

• confine the rotation of one single bond, while for the latter, it would confine two single bonds. Jiang and Huc and co-workers successfully utilized the five-membered N–H···Cl hydrogen bond to construct quinoline amide-derived double helices [53]. C–H····X (X = OR, F) hydrogen bonding-driven 1,2,3

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• Magnus Morten Martin Hennum Tore Bonge-Hansen Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, NO-0315 Oslo, Norway 10.3762/bjoc.11.210 Abstract In this letter, we report a novel synthesis of ethyl quinoline-3-carboxylates from reactions between a series of indoles and

• halodiazoacetates. The formation of the quinoline structure is probably the result of a cyclopropanation at the 2- and 3-positions of the indole followed by ring-opening of the cyclopropane and elimination of H–X. Keywords: catalysis; cyclopropanation; indole; quinoline; Rh(II); ring expansion; Introduction The

• ][8]. Hence, the anticipated initial product from the reaction would be the bottom structure in Scheme 2. However, the only isolated product from both reactions was ethyl quinoline-3-carboxylate (top structure in Scheme 2). Even though we obtained the ethyl quinoline-3-carboxylate from the thermal

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• engineering [23]. In light of this emerging propensity of cholesterol-based architectures to assimilate a plenty of pharmacological activities, cholesterol was propargylated, then reacted with azido-modified quinoline and glucopyranosyl derivatives as part of a previous study [24] to discover new

• constant due to a weak equatorial–diaxial coupling. Compounds 36 and 38 were subjected to reductive debenzylation. While, compound 38 could be debenzylated in excellent yield, quinoline derivative 36 could not be debenzylated even in the presence of Pd(OH)2. Consequently, it might be concluded that bulky

• substituents such as cholesterol and quinoline hindered the complete reductive debenzylation, at least under the described conditions. Biology The antibacterial activity of selected newly synthesized cholesterol conjugates was evaluated in vitro against E.coli (ATCC 11775) and S. aureus (ATTC 12600) according

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• -nitrobenzoyl)acetate to give a β-keto amide. The resulting amide was subjected to a Knorr cyclization in the presence of polyphosphoric acid to afford a quinolinone, which was further reduced to a quinoline in two steps. The Sandmeyer reaction permitted the replacement of the amide function with a carboxylic

• was subsequently transformed into a quinolone benzyl ether under reflux conditions. A quinoline triflate ester was prepared from the quinolone and coupled to trimethyl(2-nitrophenyl)stannane by Stille coupling catalyzed by palladium acetate. The afforded nitrophenylquinoline was hydrolyzed and

• phosporus pentachloride to prepare 4-chloro-8-methoxy-5-nitroquinoline and secondly with triflate anhydride, dimethylaminopyridine, and 2,6-lutidine to prepare 8-methoxy-5-nitro-4-triflylquinoline. The Suzuki cross-coupling was carried out on both quinoline derivatives in the presence of a palladium

Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity

• Karolina Żukowska,
• Eva Pump,
• Aleksandra E. Pazio,
• Krzysztof Woźniak,
• Luigi Cavallo and
• Christian Slugovc

Beilstein J. Org. Chem. 2015, 11, 1458–1468, doi:10.3762/bjoc.11.158

• Arabia 10.3762/bjoc.11.158 Abstract Two ruthenium olefin metathesis initiators featuring electronically modified quinoline-based chelating carbene ligands are introduced. Their reactivity in RCM and ROMP reactions was tested and the results were compared to those obtained with the parent unsubstituted

• ), releasing the desired complexes 14 and 15 as trans-dichloro isomers in good yields. Based on the previously reported trans–cis isomerization of the parent quinoline-based complex 5a, a potential isomerization of 14 and 15 was investigated. Reaction conditions for the isomerization of 5a (complete

• towards the cis-dichloro configured form (TS1cis). The energetic preference of the concerted over the dissociative pathway is decreasing when substituents in 2 position of the quinoline ligand are present. For 14 and 15 the transition state for the generation of the catalytically active 14-electron

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• and SrCO3 or AgNO3 as an activator in pyridine or quinoline [15][31], but it was unsuccessful. TLC monitoring revealed that most of icartin was still unreacted even prolonging the reaction time to 48 h. To our delight, switching the solvent to DMF/CHCl3 and the activator to Ag2CO3 made the reaction to

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• ][17][18]. Moreover, various species of` PAEs with quinoline [19][20], quinoxaline [21][22], thiadiazole [17][23], carbazole [18][24], 1,2,4-triazoles [25], thiazole [26] and azametallocyclic [27] units incorporated into a polymer chain have been described. Since ligands based on pyridazine rings can

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• acts to suppress the signaling pathways mediated by VEGFR2, inducing apoptosis in endothelial cells. Quinoline-substituted phenols To date, quinolone-substituted phenols (Qsps) have not been reported as natural secondary metabolites, although quinolone and alkylated phenols are common structural

• elements of secondary plant products. The quinoline skeleton is present in alkaloids derived from tryptophane-like quinine or camptothecine, whereas alkylated phenols with a varying alkyl side chain length are common metabolites from the shikimate pathway. Qsps were reported in a recent patent [50] to be

• developing in the eyes and in the trunk. Quinoline-substituted phenols were identified as being active based on a significant inhibition of the hyaloid vessel formation in the zebrafish model. The synthesis of two representative compounds, 20 and 23, of this class are shown in Scheme 4 and Scheme 5

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• specific delivery of drugs to the desired place of action lowers the adverse effects associated with conventional chemotherapy tremendously [3]. Therefore, much effort is continuously being made to develop novel drug-carrier systems. (S)-Camptothecin (CPT) is a natural cytotoxic quinoline alkaloid with a

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• formation of products 50–54 (Scheme 10). The ortho-acetoxylation of compounds containing picolinamide and quinoline-8-amine moieties (55 and 56, respectively) with the Pd(OAc)2/PhI(OAc)2 system in a AcOH/Ac2O mixture, resulting in the formation of products 57, 58, was performed at higher temperature (150 °C

• quinoline-8-amine directing moiety was used for copper-catalyzed aerobic ortho-aryloxylation and alkoxylation of arenes 59 with electron donating or electron withdrawing substituents to afford products 60 [66] (Scheme 12). The method is applicable to a wide range of OH-reagents; the molar ratio OH-reagent

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

• generation of Huisgen’s 1,4-dipoles are aromatic heterocycles such as N-alkylimidazole, pyridine, quinoline, isoquinoline and primary aromatic amines. In recent years, other nitrogen-containing nucleophiles such as hydrazine and arylhydrazines are also used to generate Huisgen’s 1,4-dipoles in domino

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• compounds in moderate to good yields under mild reaction conditions. Keywords: alkyne; azide; cycloaddition; cyclization; quinoline; Introduction The synthesis of N-sulfonylketenimines via CuAAC (copper-catalyzed azide–alkyne cycloaddition) between terminal alkynes and sulfonyl azides has staged for a

• found that these 3o-propargyl alcohols were more productive compared to the above 2o-propargyl alcohols. Thus 2c–f were subjected to the standard reaction conditions with various sulfonyl azides to get the corresponding 4-alkyl-substituted quinoline derivatives 9j-o in 48–77% yields. In further

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• : aromatic quinoline and chiral aliphatic quinuclidine, and a hydroxy function on the stereogenic carbon atom. Such an architecture combined with the presence of nucleophilic and electrophilic centers buried in a hydrophobic environment predestinates the molecule to asymmetric applications, such as: chiral

• ’ protons of the quinoline system. This proximity is achievable only in the case of location of vinyl and quinoline protons at the same side of the double bond. Theoretical prediction of the H12 NMR chemical shift provided an additional confirmation [39]. The δ calculated for the Z arrangement (geminal

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

• ; cyclization; Diels–Alder; inverse electron demand; N-acyliminium ion; tert-enamide; Introduction Fused indoline, isoindoline, quinoline and isoquinoline substructures are found in many natural products and bioactive synthetic compounds (Figure 1). For example, nuevamine is a naturally-occurring isoindolo[1,2

• ], and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment [10]. We are interested in the isoindolo[2,1-a]quinoline skeleton (Figure 1) due to its structural similarities with these alkaloids. The most common method of synthesizing

• 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

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• the above catalytic system. To the best of our knowledge, this is the first report of the application of this catalyst for the regioselective 1,3-dipolar cycloaddition reaction, involving azomethine ylides derived from structurally complex quinoline-based N-heterocycles. Results and Discussion Our