Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• developed an electrophilic phenylseleno trifluoromethoxylation of alkenes, which leads to β-selenylated trifluoromethoxylated compounds or, upon subsequent reduction, to the trifluoromethoxylated ones. Keywords: DNTFB; electrophilic addition; fluorine; selenium; trifluoromethoxy; Introduction Due to the

• moieties is an active research field [12]. Among these emerging fluorinated groups, the association of the CF3 moiety with chalcogens is an interesting approach. In particular, the trifluoromethoxy group (CF3O) possesses valuable properties such as electronegativity [13][14], lipophilicity [15][16

• such as their volatility, their tedious and expensive synthesis and the use of toxic reagents [55][56][57][58][59][60][61][62][63][64][65]. Recently, we reported the preparation of a stable solution of the CF3O− anion (DDPyOCF3) from the cheap and commercially available 2,4-dinitro(trifluoromethoxy

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• a methoxy group were transformed into the products in good yields (3la–na). 4-(Trifluoromethoxy)iodobenzene also well participated in this reaction, affording 3oa in 65% yield. Aryl iodides having fluoro and chloro substituents underwent selective C–I bond cleavage to provide monoalkylated products

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

• trifluoromethoxy group (OCF3), a longer reaction time of 6 hours was required to obtain the product 4c in decreased yield (57%). Photophysical properties. We studied the steady-state absorption and emission of selected tetrahydroacridines 4a–d to gain insights into their photophysical properties. The UV–vis

• the trifluoromethoxy-substituted derivative 4c, a larger red shift of 23 nm was observed. The optical gap energies of tetrahydroacridines 4a–d were estimated from the onset point of the absorption spectra [65]. The parent derivative 4a shows an onset of absorption at 363 nm and its optical band gap

• broad bands ranging from 365 to 500 nm (Figure 3). The emission spectrum of 4a appeared as a blue emission at 393 nm. Trifluoromethoxy derivative 4c exhibited a red shift of 10 nm as compared to 4a. Methoxy derivatives 4b and 4d showed similar emission bands at around 410 nm and gave larger red shifts

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

• thermally activated delayed fluorescence (TADF) emitters. In the present study, we investigate computationally the potential of other fluorine-containing acceptors, trifluoromethoxy (OCF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5), within two families of donor–acceptor TADF emitters. Time

• states between S1 and T1, thus likely leading to a very efficient reverse intersystem crossing in these compounds. Keywords: DFT calculation; pentafluorosulfanyl; spin-orbit coupling; TADF; trifluoromethoxy; trifluoromethylthio; Introduction Organic thermally activated delayed fluorescence (TADF

• within TADF emitter design (Figure 1) [25][26][27]. In the present study, we report on the impact of incorporating other fluorine-containing electron-withdrawing groups beyond trifluoromethyl (CF3), including trifluoromethoxy (OCF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5) groups, and

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• substituents, such as -CF3, -SCF3, -CF2H/-CF2-, has a range of effects on the pharmacokinetics and pharmacodynamics of the molecule [3]. Among other fluorine-based substituents, the trifluoromethoxy group (-OCF3) has until recently remained less explored and understood [4]. Nonetheless, it possesses unique

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• benzazepinone hNav1.7 voltage-gated sodium channel blockers containing 2-trifluoromethoxy-ʟ-phenylalanine derivative 189 and 3-ʟ-FPhe 190 (Figure 12) [133]. Compounds 189 and 190 were investigated as potential drugs for the treatment of neuropathic pain because they inhibited action potential firing. It was

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• has emerged as a powerful method for the construction of these compounds. This review attempts to describe the major advances in the transition-metal-catalyzed incorporation of fluorine, trifluoromethyl, difluoromethyl, trifluoromethylthio, and trifluoromethoxy groups reported between 2011 and 2019

• trifluoromethylation reported between 2011 and 2019. Meanwhile, we also present the incorporation of difluoromethyl, trifluoromethylthiol and trifluoromethoxy groups. Some sections of this review are structured around the synthesis of alkyl-, aryl- and vinyl- as well as alkynyl organofluorides. Notably, the current

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• . Herein, we present the preliminary results of these studies. Results and Discussion Urea 4a (prepared by reacting propargylamine with 4-(trifluoromethoxy)benzyl isocyanate) was reacted with an equivalent amount of benzylamine in refluxing toluene in the presence of various Lewis acids. To our delight

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• groups (Table 2, entries 2 and 3). For those bearing electron-withdrawing groups, such as halogens (F, Cl, Br), cyano, nitro, trifluoromethyl, and trifluoromethoxy groups, the corresponding products 3ad–3aj were obtained in good to excellent yields of 67–96% (Table 2, entries 4–10). It was found that the

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• determined by 19F NMR analysis using benzotrifluoride (BTF) or (trifluoromethoxy)benzene as an internal standard. bIsolated yield. c4 equivalents of CF3CF2Cu reagent were used. Perfluoroalkylation reactions of arylboronic acids. aIsolated yield. bDMF was used instead of toluene as a solvent. c4 equivalents

• Cu-catalyzed aromatic trifluoromethylation. The yield was determined by 19F NMR analysis using (trifluoromethoxy)benzene as an internal standard. Plausible mechanism of Cu-catalyzed aromatic trifluoromethylation [53]. Acknowledgements The financial support of the Ministry of Education, Culture

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

• trifluoromethoxy group meta to the directing group shuts down the reaction completely. Other directing groups were investigated. When hydrogen was replaced by methyl on nitrogen in the starting acetanilide, no reaction occurred; on the other hand, N-pivaloyl- and N-benzoylanilines were trifluoromethylated, albeit

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• spectra recorded by us. Additionally, in order to confirm the structure we used X-ray analysis for one of our products. The analyzed crystal of 3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-nitro-1H-pyrazole (3k) was a monocrystal recrystallized from diethyl ether (Figure 1). It forms a monoclinic unit cell

• functionalized with an aryl substituent on a ring nitrogen atom. X-ray structure of 3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-nitro-1H-pyrazole (3k) with 60% probability ellipsoids. Methods of synthesis of 3-nitro-1-phenyl-1H-pyrazole (3a) described in the literature. Cross coupling of 3-nitro-1H-pyrazole (1a

• and characterization of products. Supporting Information File 346: Crystallographic information file (structure of 3-nitro-1-[4-(trifluoromethoxy)phenyl]-3-nitro-1H-pyrazole). Acknowledgements This work was supported by the European Community from the European Social Fund within the RFSD 2 project.

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• have been developed [8]. Despite obvious parallels with human ALS, to date these transgenic mouse models have proven ineffective in producing potential drug therapies [6]. Many drugs that show efficacy in mouse models have been unproductive in patient trials. Furthermore, riluzole [6-(trifluoromethoxy

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• the relative basicities of aryllithiums bearing methoxy, chlorine, fluorine, trifluoromethyl and trifluoromethoxy substituents at the ortho, meta, and para positions. Equilibration studies of two aryllithiums of comparable basicity with the corresponding bromo- or iodoarenes allowed them to determine

Intramolecular hydroxycarbene C–H-insertion: The curious case of (o-methoxyphenyl)hydroxycarbene

• Dennis Gerbig,
• David Ley,
• Hans Peter Reisenauer and
• Peter R. Schreiner

Beilstein J. Org. Chem. 2010, 6, 1061–1069, doi:10.3762/bjoc.6.121

• -consistent double-ζ basis set (cc-pVDZ) by utilizing density functional theory (DFT) optimized geometries (M06-2X/cc-pVDZ) with zero-point vibrational energy (ZPVE) corrections. Exchange of the methoxy for a trifluoromethoxy group successfully prevents insertion and (o-trifluoromethoxy)benzaldehyde is

• ] (Scheme 5). Matrix isolation studies on [(o-trifluoromethoxy)phenyl]hydroxycarbene Exchanging the methoxy group for a trifluoromethoxy moiety should prohibit the insertion reaction due to the much stronger carbon–fluorine bond compared to the carbon–hydrogen bond. HVFP of [(o-trifluoromethoxy)phenyl

• ]glyoxylic acid (10) at 600 °C (500 °C, 800 °C) and subsequent matrix isolation gave (o-trifluoromethoxy)benzaldehyde (11); as expected, no insertion product (13) was detected (Scheme 6). Contrary to our findings on hydroxycarbenes, [(o-trifluoromethoxy)phenyl]hydroxycarbene (12) was not detected. Instead

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• -(trifluoromethoxy)biphenylyl-2′-diazonium salts such as 19a (R=H) through in situ generation of a trifluoromethyloxonium salt. The yield of trifluoromethylated products was highly dependent on the counteranion as observed in the trifluoromethylation of phenol (Scheme 17) [23]. The synthetic application of thermally

• phosphides (MPPh2) gave only trace amounts of the trifluoromethylated product [34][35]. The reaction of phenols with reagent 35 was investigated. From 2,4,6-trimethylphenol, the expected 1,3,5-trimethyl-2-(trifluoromethoxy)benzene was obtained only in poor yields in the range 4–15%. The trifluoromethylation

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• substituent, the trifluoromethoxy group, which is finding increased utility as a substituent in bioactives, but it is still perhaps the least well understood fluorine substituent in currency. The present review will give an overview of the synthesis, properties and reactivity of this important substituent

• group (−CF3) confers increased stability and lipophilicity in addition to its high electronegativity [5][6][7][8][9]. However, another fluorinated substituent, the trifluoromethoxy group, is becoming more and more important in both agrochemical research and pharmaceutical chemistry [10][11]. The

• trifluoromethoxy group is perhaps the least well understood fluorine substituent. When asked to draw up a list of textbook substituents, hardly anyone would consider associating such an "exotic entity" like trifluoromethoxy to the lasting popularity of the carboxyl, acetyl, formyl, nitro, amino, hydroxyl and sulfo