Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• equivalents to react with various nucleophilic reagents [90]. In 2014, Heimgartner et al. first developed the condensation reaction of a commercially available fluoral hemiacetal with acylhydrazides to yield trifluoromethylated acylhydrazones, and these fluorinated compounds underwent heterocyclization

• acylhydrazones in recent years have been summarized and discussed. The resultant fluorinated building blocks provided a facile and rapid approach to directly construct valuable nitrogen-containing fluorinated compounds. Apart from the regular involvement of addition and annulation reactions, the exploitation of

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

• -fluorinated molecules [1][2], their incorporation in various scaffolds afforded high value-added compounds as demonstrated by their numerous applications in the industrial sector such as drugs, agrochemicals, and materials. To further illustrate the ubiquity of fluorinated compounds, almost 20% of

• source in the presence of PIDA. Hence, an efficient access to the corresponding monoether derivatives 54 and 56 in 71% and 65%, respectively, were obtained. Conclusion In summary, this review provides an overview of the major developments made over the last years for the synthesis of fluorinated

• compounds by transition-metal-catalyzed C–H bond activation. This review focused on the construction of C(sp2)–XRF bonds and C(sp3)–XRF bonds with an emphasis on the trifluoromethylation reaction and transformations using emergent fluorinated residues (SCF3, SeCF3, SCF2H, SCF2CO2Et or OCH2CF3 groups). Well

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• ][16][21], the ether-linked compounds 4–6 exhibited strong activity with IC50 values of 0.2–1.2 µM, whereas compounds 7–9 with the removal of the phenyl ring from the ether methylene group resulted in a loss of potency at the tested concentrations. For fluorinated compounds, previous studies [14

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• highly halogenated carbon centers, which enable halothane to participate in various reactions such as homolysis of carbon–halogen bonds and deprotonation. Multi-fluorinated compounds such as HCFC-133a (CF3CH2Cl) and HFC-134a (CF3CH2F) have been widely used in reactions with a variety of nucleophiles to

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. Mono- or multi-fluorinated compounds were obtained in good yields (30–47%) with average DPs ranging from 9 to 15. The multifluorinated compound crystallized in a new cellulose allomorph. AFM and TEM images confirmed the formation of long platelets for monofluorinated compounds, similar to those

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• naphthoquinone-derived products and low-intensity bands in the visible region (≈400 nm) for the anthraquinone series. Keywords: [3 + 2]-cycloadditions; fluorinated compounds; fused pyrazoles; N-heterocycles; nitrile imines; 1,4-quinones; Introduction The 1,4-quinone scaffold belongs to the most important

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• purposes. Recently, a proliferation of methods has allowed easy access to a particularly desired class of these compounds: singly fluorinated compounds such as fluoromethyl ethers [1]. Still missing from the chemist’s toolkit, however, are means to construct their more highly oxidized analogues

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• important element in the broader space of chemical biology [2]. Many commercial and industrial compounds are fluorinated, including refrigerants, degreasers, drugs, pesticides and anti-stick materials, and consequently there is a high degree of interaction between fluorinated compounds and nature [3

• ]. Furthermore, owing to the lack of naturally-occurring fluorinated compounds, fluorine is a useful probe to investigate structure and mechanism of biological molecules. Central to these studies is fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), which allows the user to readily visualize changes

• -B24674, which revealed the presence of a fluorinase gene, suggesting that the microorganism could produce fluorinated compounds from fluoride ion. This was confirmed by 19F NMR of culture supernatant after the bacterium was grown in medium containing 2 mM fluoride ion. Furthermore, because of the large

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• subsequent decarboxylative trifluoromethylthiolation were performed in a one-pot fashion. Keywords: decarboxylation; fluorinated compounds; pyridine compounds; trifluoromethylthiolation; Introduction The pyridine ring is found in numerous biologically active compounds. Therefore, efficient methods for

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• eV in zeonex [20]). The corresponding ΔEST values are generally smaller than those of the Type I fluorinated compounds with values of 0.08 eV for 2CzTRZ, 0.09 eV for 2CzBP and 0.18 eV for 2CzBN; however, the similar orbital symmetries between S1 and T1 would render rISC between these two states less

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• of the peculiar properties of the fluorine atom, fluorinated compounds gained a growing interest over the last decades and found applications in a large panel of fields from materials to life sciences [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Fluorinated motifs bring to molecules specific

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• lipophilicity, metabolism, binding, and bioavailability are often beneficial [1][2][3][4][5][6][7][8][9]. Fluorinated organic compounds are common amongst drugs [8][9], and the synthesis of fluorinated compounds has become a rapidly developing area [9][10][11][12][13][14][15][16][17][18]. In addition to

• transformation, and COOH→CF3 transformation), is also an important nucleophilic fluorination method [2][3][4][5][10][11][18]. The synthesis of fluorinated compounds via deoxyfluorination [21][22][23][24][25][26][27][28][29][30] or utilizing sulfur fluoride deoxyfluorinating reagents [31][32] is a highlighted

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• lipophilicity with the molecular conformation. Keywords: dipole moment; fluorinated compounds; gauche effect; herbicides; log P; Introduction Whilst in the last years the agrochemical industry has encountered a period of downturn affected by new regulations, low crop prices, biochemical resistance, among

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• (compare E1 with F1). A much lower lipophilicity decrease is seen when converting the acyclic β-fluorinated compounds D2 and G2 to the cyclopropyl analogue E2, but an appreciable logP decrease is still seen going from E2 to the oxetanyl derivative F2. With γ-fluorination, the logP decreases are similarly

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• discussed in detail. The focus of this review is to highlight the efforts made in the field of the Pauson–Khand reaction with fluorinated compounds for the preparation of bicyclic derivatives. Review The Pauson–Khand reaction The Pauson–Khand reaction (PKR) formally consists of a [2 + 2 + 1]-cycloaddition

• in natural products, pharmaceuticals and other added-value compounds accounts for the great applicability that this reaction has found [26][27][28][29][30][31][32]. Despite the increasing demand of fluorinated compounds and the impressive development of the PKR, the combination of these two fields

• 1,7-enynes 34 were prepared in three steps from sulfinylimines derived of o-iodobenzaldehydes. A variety of fluorinated compounds bearing fluorine or fluoroalkyl groups attached to the aryl moieties were efficiently prepared (Scheme 15). In this report, the suitability of enynes bearing CF3

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• materials. Keywords: alkyne oxidation; benzils; bistolanes; fluorinated compounds; phosphorescence; Introduction The development of organic light-emitting molecules is recognized as one of the most important studies because of the broad application of these compounds as fluorescence probes, bio-imaging

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• were used to investigate this behaviour. DSC measurements Phase transition temperature (Tt), melting temperatures (Ti) and enthalpy changes (∆Ht) of compounds 2 and 4 are summarized in Table 2. Based on the data given in Table 2, we found that fluorinated compounds present supplementary transition

• temperatures compared with the hydrocarbonated analogues. DSC thermograms of fluorinated compounds 2b, 4a and 4b are shown in Figure 1. The thermogram of derivative 2b presents only one peak between the crystalline and the isotropic phase in cooling. However, it exhibits two peaks in heating which indicates

• lead on a deep study in order to investigate other parameters such as response time, viscosity and dielectric anisotropy. DSC thermograms of fluorinated compounds 2b, 4a and 4b recorded at 5 °C/mn at heating (down traces) and cooling (top traces) cycles. Optical texture (×10) of liquid crystal phase

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• (bc-DNA) and tricyclo-DNA (tc-DNA) scaffold. All these modifications unveiled an either identical or slightly increased affinity versus complementary RNA compared to their non-fluorinated compounds [32][33][34][35]. Interestingly, the 2’F-tc-ANA (Figure 1) exhibited in a sequence- and composition

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• electron transfer generates the benzylic cationic intermediate A, which affords the benzylic fluorinated product. It is known that benzylic fluorinated compounds are known to be generally prone to lose a fluoride anion [26]. On the other hand, intermediate A may undergo also elimination of a β-proton due

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• iodide (PI): Cytotoxicity was detected with the MuseTM Annexin V and Dead Cell Assay Kit (Merck Millipore Corp., Darmstadt, Germany) and Muse Cell Analyzer (Merck Millipore Corp.) according to the manufacturer’s protocols. Cells incubated in the presence or absence of the fluorinated compounds for 24 h

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• drugs contain fluorine atoms or fluoroalkyl groups, representing 150 fluorinated molecules, and this trend is expected to increase to about 30% in the early future as a new generation of fluorinated compounds is currently in Phase II−III clinical trials [1]. In parallel, pharmaceutical peptides are

• a free amine is crucial to establish ionic interactions with acidic residues of Aβ1-42 [15][39][40][41]. No activity was observed at a 1:1 ratio for the fluorinated compounds 3b and 4b, while an increase of the fluorescence plateau was observed in the presence of the Ser and Thr containing compounds

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• , fluorinated compounds have been the subject of growing interest [1][2]. The specific properties introduced by fluorinated groups have contributed to the “success story” of fluorinated molecules. Nowadays, fluorinated compounds find applications in various fields, from life sciences to materials [3][4][5][6][7

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• applications of fluorinated compounds in life and materials science, developing efficient and straightforward methods for the synthesis of fluorinated compounds has become more and more important. Although great achievements have been made in the introduction of fluorine atom(s) into organic molecules over the

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• to metabolism and oxidation compared to non-fluorinated compounds. In addition to their stability, perfluorinated compounds exhibit non-tackiness, low friction, and the ability to repel water and oil [24]. Therefore, they are used as functional materials such as fluorocarbon polymer. Fluorine is also

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics

• Forrest S. Etheridge,
• Roshan J. Fernando,
• Sandra Pejić,
• Matthias Zeller and
• Geneviève Sauvé

Beilstein J. Org. Chem. 2016, 12, 1925–1938, doi:10.3762/bjoc.12.182

• routinely obtain because they are obtained under similar conditions as the new results with the fluorinated compounds. Zn(L2–L4)2 showed an increase in PCE compared to Zn(WS3)2, due to an increase in JSC. This points to a generally positive effect of fluorination on device performance. The current best