Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• % yield, 19a, 84% yield), substituted pyrazole derivatives (6 examples, up to 55% yield, 19b, 55% yield), pyrimidine (19c, 31% yield) as well as quinoline and isoquinoline (19d and 19e, 65% and 66% yields, respectively). In addition, the trifluoromethylthiolated benzo[h]quinoline 20f was obtained in good

• bonds did not have a significant impact on the outcome of the reaction. It should be noted that this methodology afforded the products with a high regioselectivity, and no incorporation of the SCF3 moiety on the benzylic or at the C5 position of the quinoline part of the directing group was observed

• [h]quinoline under palladium catalysis in the presence of PhI(OAc)2 as oxidant (Scheme 19) [161]. Since this seminal work and in the course of their investigation towards the development of new methods for the alkoxylation of C(sp2) centers by transition-metal catalysis, few examples of transition

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reactions, as pseudo-heteroarylzinc reagents. Another example developed by Knochel uses the zincated 1,4-dithiin 22 as a nucleophile to add across the N–O bond in anthranil [44], which spontaneously cyclizes to a heterocycle-fused quinoline via a Friedel–Crafts-type pathway onto the released aldehyde moiety

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• propargylated, coupled with azido quinoline, and then functionalized with glucose as part of random designs to discover new antimicrobial and cytotoxic candidates. From these studies, conjugates I [9] and II [10] were identified to display an excellent preliminary antibacterial impact, and congener III [10

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• Abstract The acceptorless dehydrogenative coupling (ADC) reaction is an efficient method for synthesizing quinoline and its derivatives. In this paper, various substituted quinolines were synthesized from 2-aminobenzyl alcohols and aryl/heteroaryl/alkyl secondary alcohols in one pot via a cyclometalated

• , quinoline and its derivatives widely exist in natural products. They have a wide range of biological activities, such as antibacterial [1], anti-inflammatory [2], antitumor [3], antihepatitis C (HCV) [4], antituberculosis (TB) [5], antimalarial [6], and anti-Alzheimer's disease (AD) [7]. Among these

• . Therefore, it is still of great significance to develop new and broad-spectrum quinoline antibacterial agents, and the research on antibacterial quinolines is one of the most promising and dynamic research fields in contemporary anti-infective therapy. For example, Eswaran's group [9] synthesized some 1,2,4

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• pentacyclic, antiproliferative quinoline alkaloid camptothecin (65), Peters et al. used an α-ketoester moiety in an auxiliary controlled approach towards the only stereogenic center present in the natural product (Scheme 10) [25]. First, the ketoacid 60 was esterified with 8-phenylmenthol (61) to yield the α

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• formaldehyde or ketone groups could also be transformed into the desired diphosphination products 3bm and 3bn in moderate to good yield. The generality of the system was further showcased by tolerating quinoline and isoquinoline groups, and the desired products 3bp and 3bq were afforded in a high yield

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• aqueous lithium hydroxide, THF, 4 h, 94% [15]; e) copper powder, quinoline, 230 °C, 1 h, 81% [15]; f) N-bromosuccinimide, CHCl3/glacial acetic acid, 0 °C, 1 h, rt, 1.5 h, 94% [15] ; g) n-BuLi, −90 °C, 20 min, triisopropyl borate, −80 °C, anhydrous THF, rt, overnight, 97% [34]; h) pinacol, toluene, 115 °C

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• co-workers prepared quinoline-fused 1,2-azaphospholine 2-oxides 217 in approximate 80% yield from 2-azidoquinoline-3-carbaldehydes 216 and tris(dimethylamino)phosphine in THF with water as solvent. It was mentioned that 2-azidoquinoline-3-carbaldehyde 216 and tris(dimethylamino)phosphine first

• phosphorus electrophiles with (R)-1-tert-butyl-1,1-diphenyl-N-(1-phenylethyl)silanamine (204). Synthesis of 2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) from 3-(phenylaminomethylene)-2-phenylamino-6-methyl-2,3-dihydro-4H-chromen-4-one (213) and diethyl phosphite. Synthesis of quinoline

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• both quinoline and pyridine as N-containing heterocycles rich in electrons, which are the key structural factors leading to acid discoloration. At the same time, Kappaun et al. synthesized a series of conjugated alternating and statistical copolymers (poly[2,7-(9,9-dihexylfluorenyl)-alt-(2,6-pyridinyl

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• farnesylation of quinoline derivatives, such as 8-hydroxyquinoline-2-carboxylic acid (8-HQA) and quinaldic acid. The results of this study provide new insights into the abundance and diversity of Ptases in marine Flavobacteria and beyond. Keywords: Flavobacteria; prenylation; Saccharomonospora; UbiA-like

• obtained after washing and ultracentrifugation. Substrate specificity of UbiA-297 Based on our in silico analysis and previous mass-spectrometry-guided metabolomic analysis of marine Flavobacteria and members of the genus Saccharomonospora [29][30], we anticipated hydroxylated aromatic or even quinoline

• ). As depicted in Figure 5, farnesylated products were detectable for six out of 14 tested aromatic acceptor substrates by HRMS/MS (Figures S4–S8 in Supporting Information File 1). In particular, quinoline-type substrates, such as 8-HQA and quinaldic acid, were transformed, while only moderate

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• -(1H-1,2,4-triazol-1-yl)-1H-pyrazol-1-yl)quinoline (3b) and 7-chloro-4-(3-((4-chlorophenyl)thio)-5-(dichloromethyl)-4-nitro-1H-pyrazol-1-yl)quinoline (9e) inhibited the growth of the chloroquine-sensitive Plasmodium falciparum strain 3D7 with EC50 values of 0.2 ± 0.1 µM (85 ng/mL, 200 nM) and 0.2

• , such as 7-chloro-4-(4-trimethylsilylethynyl-1-pyrazolyl)quinoline at 100 ppm which gave a 100% curative effect in barley infected with barley powdery mildew [23]. A statistical model to predict the structural requirement of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)chloroquine derivatives to inhibit

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• give 1-amino-4-butylaminoanthraquinone. Similarly, quinoline-5,8-diones react with amines under catalysis with Ni(II) ions to selectively give substituted amino derivatives [101][102]. The same group demonstrated that the reactions between β-NQS 18 and N,N’-dialkylanilines or 1,1-bis[p(dimethylamino

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• aqueous photocleavage in the presence of triethylamine, and the resulting reaction mixture was purified by reversed-phase HPLC (Figure 2). We isolated a nitroso product 3, in addition to two other major identifiable components of the crude reaction: quinoline N-oxide (4) and quinolinone (5). The compounds

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• more polar solvents (DMSO; 65–150 nm and MeOH; 65–130 nm) than in CHCl3 (59–85 nm). Compounds 3 presented good stability under white-LED irradiation conditions and moderate ROS generation properties were observed. Keywords: photophysical properties; photostability; quinoline; ROS generation; Schiff

• literature by our research group [14]. With the quinolines 1a–f at hands we initially selected quinoline 1b and salicylaldehyde (2a) to optimize the reaction conditions leading to Schiff bases 3. Hence, the reaction solvent and molar ratio between the precursors were evaluated. The reactions were carried out

• ). Based on these results, we selected acetonitrile as the best solvent for further optimization. When changing the molar ratio of the reactants to a 1:2 molar ratio of quinoline 1b and salicylaldehyde (2a), the yield of the desired product 3ba increased to 90%. The best result was obtained when quinoline

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• (Brønsted acidity/basicity, hydrogen-bonding units, and counter-anions toward metals) [48][49]. In 2019, Shi, Lin, and co-workers achieved an enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers via Pd-catalyzed C–H olefination of 8-phenylquinoline (11) using a novel chiral

• spirophosphoric acid (CPA 4). A wide range of quinoline-derived biaryls 13 with various substituents was synthesized in good to excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee) (Scheme 5). A working model for the origin of enantioselectivity in C–H olefination was provided by

• -naphthol derivatives. Enantioselective synthesis of multisubstituted biaryls. Enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers mediated by chiral spirophosphoric acid catalyst CPA 4. Pd-Catalyzed atroposelective C–H olefination of biarylamines. Palladium-catalyzed directed

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• and, as expected, the cyclohexane ring is not involved. In all cases, the electron densities of HOMO were localized in the π-bonding orbitals between the carbon backbone of the quinoline ring and its two external phenyls. The LUMO electron densities were mainly located in the π* antibonding orbitals

• surfaces around the phenyl groups leading to a significant decrease in their electronic densities. However, thanks to the π-donating effect of two methoxy groups for 4b and 4d, yellow-red regions are present in the phenyl groups and quinoline core. The electrochemical behavior of compound 4c was studied by

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• , the reactions were carried out under base-free conditions. It was found that urea-based catalysts outperformed squaramide derivatives, and that the installation of a chlorine atom adjacent to the catalyst’s quinoline moiety aided in avoiding selectivity-reducing complications related to the production

• to the ability of squaramides to bind anionic species more strongly than ureas. The moderate enantiocontrol observed thus far prompted us to posit that the nitrogen atom on the quinoline moiety of the catalyst could participate to the deprotonation of 5a, therefore, leading to less selective

• alkylation. In order to test this hypothesis, we designed novel dihydroquinine-derived catalysts of general type 9 bearing an electron-withdrawing substituent at the C-2' position with the intent of lowering the basicity of the quinoline ring. In addition, we prepared a C-2'-phenyl-substituted dihydroquinine

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• activation proposal was later on reported from the Takemoto group in 2007, where the less reactive quinoline derivatives 23 were employed in a thiourea-catalyzed Reissert reaction (Scheme 5b) [37]. In both cases, however, the binding mode of the catalyst can rather be described by the formation of a close

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• catalyst to perform a regioselective scandium-catalyzed alkylation of 2-phenylquinoline derivatives (Scheme 3B) [38]. It is important to highlight the biological importance of quinoline derivatives, since several quinolines are known to present valuable biological activities, such as anti-HIV (5) [48

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• thiazole and quinoline, TO fluorescence is almost completely quenched in ssPNA, but increases significantly upon hybridization to the complementary DNA [150]. The intercalation of TO in PNA–DNA duplex restricts rotation around the methine bond enforcing planarity of the two TO’s aromatic system, which

• base pairs in dsRNA [153][154]. Replacement of thiazole in TO with another quinoline gives bis-quinoline (BisQ, Figure 10), a red-shifted PNA nucleobase analogous to TO [155]. Although binding of BisQ with all four natural DNA nucleobases has not been explored in detail, BisQ-modified FIT PNAs showed

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• the quinoline core and its two arylethynyl groups. As shown in Figure 2, the unsubstituted derivative 4a exhibited wide bands with two maxima at 346 and 365 nm. A methyl group at the ortho position have a minor impact and derivative 4b showed similar optical transitions with a slight red shift. While

• attributed to intermolecular charge transfer between the oxygen lone pair electrons and the quinoline core. The unsubstituted derivative 4a presents an onset of absorption (λonset) at 389 nm and its optical band gap was deduced to be around 3.18 eV. Tetrahydroacridines 4e and 4f showed approximately the same

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• -amidinopyrazole under the same reaction conditions. Edmont et al. extended this method using hydrazides as nucleophiles to produce potential hypoglycemic quinoline carboxyguanidine derivatives (Scheme 33) [70]. In this case, the “biguanidylation” reagent could convert the hydrazide into the desired compound

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• ). Abonia and co-workers [85] established a catalyst-free construction of quinoline-based pyridopyridines 97 by employing a microwave-assisted three-component reaction of 3-formyl-2-oxoquinoline derivatives 95, 2,4,6-triaminopyrimidine (96) and a cyclic 1,3-diketone such as dimedone (6a) in DMF. The

• opening resulting in imine intermediate E. A consecutive intramolecular cyclization and tautomerization yields azepino[5,4,3-cd]indoles 143b. 9 Quinolines Quinolines are bicyclic aromatic heterocycles consisting of a fused pyridine and benzene ring. Quinoline and its derivatives are important both from

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• phenanthridine 38 (also including quinoline products, Scheme 12). In this way, a nitrogen-centered radical was given via the EDA complex that was initiated by single-electron transfer, accomplishing the synthesis of a variety of highly functionalized nitrogen-containing aromatics with excellent yield. In 2019