Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• diagnostic for the structures proposed. A nitro group ortho to a fluorine atom on the aryl ring is necessary under the present conditions to achieve full conversion of the starting fluoroarene. In related experiments, we found that a para-trifluoromethyl group is not sufficiently activating for reaction to

Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)-3H-1λ³,2-benziodaoxol-3-one

• Nico Santschi,
• Roman C. Sarott,
• Elisabeth Otth,
• Reinhard Kissner and
• Antonio Togni

Beilstein J. Org. Chem. 2014, 10, 1–6, doi:10.3762/bjoc.10.1

• % average yield of five experiments). This step was routinely carried out on a 3 gram scale in less than 5 minutes. Finally, introduction of the trifluoromethyl group was achieved by stirring 6 and anhydrous KF in hot MeCN, followed by treatment with Ruppert–Prakash reagent (TMSCF3) at 0 °C yielding 10–35

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• mentioned above, the preparation of N-ethyl 3,3,3-trifluoropropanaldimine, the Schiff base of 3,3,3-trifluoropropanal, was accompanied by enamine formation, likely as a consequence of the acidity of the proton α to the trifluoromethyl group [45][47]. Not surprisingly, 5 was relatively reactive. After

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

• Xiao-Ping Wang,
• Jin-Hong Lin,
• Cheng-Pan Zhang,
• Ji-Chang Xiao and
• Xing Zheng

Beilstein J. Org. Chem. 2013, 9, 2635–2640, doi:10.3762/bjoc.9.299

• yields. The results provided a versatile approach for the construction of Cvinyl–CF3 bonds without using prefunctionalized substrates. Keywords: alkenes; catalysis; copper; electrophilic trifluoromethylating reagent; trifluoromethylation; Introduction The incorporation of a trifluoromethyl group into

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

• -type and the nature of the transition metal. 1 Catalytic monofluoromethylation Monofluoromethylated aromatics find application in various pharmaceutical [29][30][31][32] and agrochemical products [18]. Although numerous methods for the catalytic introduction of a trifluoromethyl group onto aryl

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

• Yuzo Nakamura,
• Motohiro Fujiu,
• Tatsuya Murase,
• Yoshimitsu Itoh,
• Hiroki Serizawa,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2013, 9, 2404–2409, doi:10.3762/bjoc.9.277

• , biological, and physical properties [1][2][3][4][5][6]. Particularly, trifluoromethylated compounds can be widely employed as one of the most effective analogues of bioactive compounds, because the trifluoromethyl group enhances the metabolic stability, lipophilicity, and bioavailability of these compounds

Direct electrophilic N-trifluoromethylthiolation of amines with trifluoromethanesulfenamide

• Sébastien Alazet,
• Kevin Ollivier and
• Thierry Billard

Beilstein J. Org. Chem. 2013, 9, 2354–2357, doi:10.3762/bjoc.9.270

• compounds for medicinal chemistry or agrochemistry [1][2][3][4][5][6][7][8][9]. More recently, new substituents have emerged which associate the trifluoromethyl group with heteroatoms such as CF3O or CF3S. Because of its high hydrophobicity (Hansch parameter πR = 1.44), the CF3S moiety is of particular

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• –cyclisation leading to indoline 97 with an intramolecular Friedel–Crafts reaction to afford a tricyclic derivative 98 substituted by a trifluoromethyl group [44]. The second exploits the presence of both a protected primary amine and an easily substitutable chlorine on the pyrimidine ring in 99a,b to afford

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• (4) compounds 2{1,6} and 6{10} are predicted to be ligands for a total of 15 protein targets. This high number of potential protein targets may be due to the electronegative trifluoromethyl group on 2{1,6} and the effect it would have on the α,β-unsaturated amide and the purported bioactivity of the

Discovery of practical production processes for arylsulfur pentafluorides and their higher homologues, bis- and tris(sulfur pentafluorides): Beginning of a new era of “super-trifluoromethyl” arene chemistry and its industry

• Teruo Umemoto,
• Lloyd M. Garrick and
• Norimichi Saito

Beilstein J. Org. Chem. 2012, 8, 461–471, doi:10.3762/bjoc.8.53

• attracted considerable interest in many areas such as medicines, agrochemicals, and other new materials, since the highly stable SF5 group is considered a “super-trifluoromethyl group” due to its significantly higher electronegativity and lipophilicity. This article describes the first practical method for

• pentafluoride; super-trifluoromethyl; Introduction Pentafluorosulfanyl (SF5) is considered a “super-trifluoromethyl group” as SF5 has the peculiarity of fluorine beyond a trifluoromethyl (CF3) group [1]. Arylsulfur pentafluorides (ArSF5) are very thermally and chemically stable [2]. Pioneering work by Sheppard

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• obtained in this reaction (Table 1, entries 1–6). Aniline 6g bearing an electron withdrawing trifluoromethyl group led to a low yield of 3g (Table 1, entry 7) whereas no cyclized product was observed with other electron-deficient anilines 6h–j and carbamate 7 (Figure 1). Other methods to react 7 with

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• a nearby phenylalanine residue, whilst the trifluoromethyl group interacts with serine and arginine residues in a lipophilic pocket (Figure 8) [83]. In the discovery chemistry route [84] the heterocycle core was prepared from a SNAr reaction between chloropyrazine (276) and excess hydrazine

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

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

• trifluoromethyl group from a reagent to a target molecule is key for the reaction, and the reagents are classified according to their radical, nucleophilic or electrophilic character. Radical trifluoromethylation can be achieved from various sources of trifluoromethyl radicals that include trifluoromethyl iodide

• act as a useful source of the highly electrophilic trifluoromethyl group but until the work of Umemoto and co-workers initiated in 1994 and published as a full paper in 2007 [23], their synthesis remained problematic. O-(Trifluoromethyl)dibenzofuranium salts 20a,b are thermally unstable compounds that

• , enamines, and thiolate anions with these reagents, albeit in low to moderate yields [28]. Neutral hypervalent iodine(III)–CF3 reagent Initial attempts by Yagupolskii and Umemoto to synthesize iodonium salts with a trifluoromethyl group were unsuccessful. Whilst iodonium salts including p

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• ]. The NOESY spectrum of peptide 64 reveals long-range through-space interactions, suggesting a folded conformation possibly reinforced by a Tyr-OH···Thr-OH hydrogen bond. In contrast, analogue 65 contains an electron-withdrawing trifluoromethyl group, which lowers the H-bond acceptor ability of the

• 65. The electron-withdrawing trifluoromethyl group of 65 disrupts a key hydrogen bond, leading to a different conformation as determined by NOESY experiments. The C–F bond influences the conformation of β-peptides. β-Heptapeptide 66 adopts a helical conformation, reinforced by the α-fluoroamide

Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me₃SiCF₂SO₂Ph and PhSO₂CF₂H reagents catalyzed by chiral quaternary ammonium salts

• Chuanfa Ni,
• Fang Wang and
• Jinbo Hu

Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21

• introduction of a trifluoromethyl group into aldehydes and ketones with Ruppert-Prakash reagent, (trifluoromethyl)trimethylsilane, Me3SiCF3 and other reagents [19][20][21][22][23][24][25][26][27][28][29]. Although one-step nucleophilic difluoromethylation with R3SiCF2H is challenging regarding generality and

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

• biggest group of fluorinated pesticides are the compounds containing a trifluoromethyl group (mainly at aromatic rings), followed by aromatic compounds containing an isolated fluorine atom (one and more). However, according to the 12th and 13th edition of the pesticide manual only five pesticides

• substituting a trifluoromethyl group for methyl on different heteroatoms. Electronegativities and Hydrophobic Parameters for various substituents. Reaction of 2-, 3- and 4-(trifluoromethoxy)phenyllithiums and electrophiles. Acknowledgements We thank the Ministère de la Recherche of France and are grateful to

• latter are unfavorable all alternative mechanisms avoiding attack at fluorine always apply in biological systems [4]. Moreover, the presence of fluorine atoms in biologically active molecules can enhance their lipophilicity and thus their in vivo uptake and transport. In particular, the trifluoromethyl