CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• ][19]. This way, they could access a variety of α-tertiary pyrrolidines carrying a β-trifluoromethyl group, in high yields and enantioselectivities (Scheme 13). The reaction conditions were compatible with various substituents on both aryl rings, as well as with unbranched substrates. Interestingly

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• small amounts in most cases. A radical mechanism was proposed as described in Scheme 41. Imidazopyridines have demonstrated many interesting features toward biological activities and the incorporation of a trifluoromethyl group into such architectures was expected to alter their properties. Therefore

• used CF3SO2Na as source of the trifluoromethyl group and a catalytic amount of anthraquinone-2-carboxylic acid (AQN-2-CO2H). The scope was achieved on arenes and heteroarenes (10 examples). Once more, electron-rich aromatic compounds were converted into the corresponding trifluoromethylated products in

• ; Introduction In organofluorine chemistry, the CF3 group occupies a place of choice as privileged structural motif in the development of multifaceted catalysts and ligands for organic synthesis as well as in the design of pharmaceuticals, agrochemicals and specialty materials [1][2][3][4]. The trifluoromethyl

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• synthesis of novel isomeric 4(6)-trifluoromethylated 1,2,3,4-tetrahydro- and perhydro-(2-oxopyrimidin-4-yl)acetic acid derivatives. Keywords: ketimines; malonic acid; Michael- and Mannich-type decarboxylative addition; pyrimidin-2(1H)-ones; regioselectivity; trifluoromethyl group; Introduction

• -containing heterocyclic compounds [24][25][26][27][28][29]. It should be noted that the presence of a strong electron-withdrawing trifluoromethyl group is responsible for the sufficient reactivity of the electrophilic ketimine function with various carbon nucleophiles in these reactions. Recently, the

• and a trifluoromethyl group. Thus, the acids 4a,g,i quantitatively yielded reduced products 9a–c under mild catalytic conditions (when reacted with hydrogen at atmospheric pressure and room temperature for 3 hours in the presence of 10% Pd/C catalyst) as shown in Scheme 1. The simplest acetic acid

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

• delivers trifluoromethylated allylic products 3 and 4. Conclusion In conclusion, we have developed an efficient method for preparation of aliphatic alkenes branched with a trifluoromethyl group by palladium catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides. The reaction proceeds

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• novel dithiocarbamates. Nevertheless, new synthetic methods towards dithiocarbamates are sought after and research in this area is still intense. The introduction of a trifluoromethyl group into organic compounds is a very productive strategy of modification of molecules for various applications in the

• been reported to introduce the trifluoromethyl group in organic structures including nucleophilic, electrophilic, radical and transition metal-mediated trifluoromethylations. Among the electrophilic trifluoromethylation methods, reagents based on hypervalent iodine (Togni's reagents I and II, Scheme 1b

• moiety of piperidine, pyrrolidine and diethylamine adducts, respectively. The results revealed that the rotational barrier in fluorinated dithiocarbamates is slightly higher than in the nonfluorinated analogue [35][38][39]. This may be attributed to a higher electron affinity of the trifluoromethyl group

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

•  1). The observed checkmark shape differs from that previously reported for an isolated partially fluorinated methyl group at the end of a saturated aliphatic chain. In the latter case, the methyl group is the most lipophilic, more than a trifluoromethyl group; and the same has been reported for the

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• containing a trifluoromethyl group at C-2 and a p-halogen-substituted and non-substituted phenyl-1,2,3-triazole moieties. The synthesis of 2-(trifluoromethyl)-6-phenylquinolone was achieved by Conrad–Limpach reaction of a primary aromatic amine with a β-ketoester [37][38]. Namely, thermal condensation of 4

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• bear the trifluoromethyl group have great importance in the life sciences and materials fields as well as discovery chemistry in general [1][2][3]. Consequently, transition-metal-catalyzed methods for preparing aromatic trifluoromethyl compounds from readily available aryl halides are an area that has

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• the position of the methyl substituent from the para to the ortho or meta positions decreases the yield in toluene. Dimethylamino and thioether groups display a lower yield with method B (34b,g) contrary to the trifluoromethyl group (34i). With p-fluorobenzonitrile the decyanation is observed with

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• , thus the complete cyclization needed longer time and the yield was relatively lower. Moreover, a chlorine atom at the aromatic ring was tolerated under these conditions. The meta-substituted starting materials 2i and 2j gave good regioselectivity. When a trifluoromethyl group was located at the meta

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• carbonylation, a number of additional substrates were assessed to determine the generality of the flow process. No significant impact was seen on the overall yield by altering the ortho-substituent to a bromo, fluoro or trifluoromethyl group. However, a slight decrease associated with the larger sizes of bromo

• trifluoromethyl group substrate 13 gave a 71% yield). For comparisons of the sizes of the ortho-substituents used, A-values can be used as a guide (Cl: 0.43 kcal/mol, Br: 0.38 kcal/mol, F: 0.15 kcal/mol, OMe: 0.60 kcal/mol, CF3: 2.10 kcal/mol and Me: 1.70 kcal/mol) [41]. This indicates interplay between

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• nitriles 4b–k including aromatic and aliphatic ones, were reacted with tetraphenylene (1) to give the corresponding carbonyl products 5b–k (Scheme 1). Both substrates containing either an electron-donating methyl group or electron-withdrawing trifluoromethyl group were suitable for the reaction. In

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• . The same year Zhao, Zhu and co-workers developed a new class of thiourea organocatalyst 145 bearing a trifluoromethyl group. The combination of this group and phenylalanine provided an efficient catalyst for the domino reaction between ethyl 4,4,4-trifluoro-3-oxobutanoate 146 and β-unsaturated α

Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

• Javier Ajenjo,
• Martin Greenhall,
• Camillo Zarantonello and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 192–197, doi:10.3762/bjoc.12.21

• than the trifluoromethyl group. Currently, the limiting factor for a more widespread use of SF5 compounds is the low accessibility of basic building blocks and the lack of understanding their chemical behavior. For aromatic SF5 compounds, two main synthetic approaches exist. The first one is a direct

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• -withdrawing character [8] – similar to but more extreme than the trifluoromethyl group – makes SF5 compounds promising candidates for agrochemicals and pharmaceuticals [9]. Recent studies showed several cases where SF5 analogues of established compounds showed improved potency [10][11][12]. Limiting factors

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

• ][2][3][4][5][6][7]. The characteristic size, strong electron-withdrawing ability, and the high lipophilicity of the trifluoromethyl group are key properties of biologically active CF3-containing molecules [8]. Perfluoroalkylcopper compounds (CnF2n+1Cu), which are soft and relatively stable

• reaction conditions of copper-catalyzed nucleophilic trifluoromethylation. Electron-rich iodoarenes underwent the nucleophilic trifluoromethylation to afford the corresponding trifluoromethylated benzenes. Furthermore, the trifluoromethyl group was introduced into naphthalenes and thiophene with hemiaminal

• . Then the trifluoromethyl group in 3 migrates to generate the trifluoromethylcopper(I) complex 5 with the elimination of N-formylmorpholine (4) [54]. Finally, Ar–CF3 is formed by the coupling of CF3Cu complex 5 with Ar–I, and CuI-diamine complex 2 is regenerated. Conclusion Fluorine has greatly

A new approach to ferrocene derived alkenes via copper-catalyzed olefination

• Vasily M. Muzalevskiy,
• Aleksei V. Shastin,
• Alexandra D. Demidovich,
• Namiq G. Shikhaliev,
• Abel M. Magerramov,
• Victor N. Khrustalev,
• Rustem D. Rakhimov,
• Sergey Z. Vatsadze and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2015, 11, 2072–2078, doi:10.3762/bjoc.11.223

• similar alkenes [38][39][40]. The trifluoromethyl group of the Z-isomers of compounds 3–5 resonates in higher field in 19F NMR (3: −72.8 ppm, 4: −67.1 ppm, 5: −69.0 ppm) than that of the E-isomers (3: −67.9 ppm, 4: −60.2 ppm, 5: −62.4 ppm). In the case of compound 3 an additional conformation can be seen

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• -workers in 1999 [19]. By employing TMEDA-activated butyllithium in THF at −75 °C, the authors mainly noted proton abstraction next to the trifluoromethyl group. A competitive minor reaction at the 2 position of the pyrrole group can be rationalized by similar pKa values at C2 and C3’ [19]. Indeed, when

• compared with a bromo substituent, the trifluoromethyl group similarly (and maybe more strongly) exhibits a long range acidifying effect, but less acidifies the ortho positions [53][54]. The lack of regioselectivity observed in the course of the reaction between the lithium–zinc base and the N-(4

Trifluoromethyl-substituted tetrathiafulvalenes

• Olivier Jeannin,
• Frédéric Barrière and
• Marc Fourmigué

Beilstein J. Org. Chem. 2015, 11, 647–658, doi:10.3762/bjoc.11.73

• the deformation of the unsymmetrically substituted dithiole rings, when bearing one, or two different EWG, and attributed to the mesomeric effect of ester or nitrile groups, is not notably modified or counter-balanced by the introduction of a neighboring trifluoromethyl group. DFT calculations confirm

• functionalized at various positions with the electron-withdrawing –CF3 (trifluoromethyl) group such as EDT-TTF(CF3) (1c) or EDT-TTF(CF3)2 (2cc) (Scheme 2) [31]. Single-crystal X-ray diffraction measurements revealed the recurrent formation of layered structures with a strong segregation of the fluorinated

• derivatives described here is shown in Figure 1 and demonstrates that the trifluoromethyl group anodic shift observed in the order CO2Me < CF3 < CN correlate well with the σmeta Hammet constant. Optical properties The evolution of the lowest energy absorption bands is also reported for the different TTF

Visible light photoredox-catalyzed deoxygenation of alcohols

• Daniel Rackl,
• Viktor Kais,
• Peter Kreitmeier and
• Oliver Reiser

Beilstein J. Org. Chem. 2014, 10, 2157–2165, doi:10.3762/bjoc.10.223

• example under typical conditions 3,5-bis(trifluoromethyl)benzoates such as 10 gave 12 where one trifluoromethyl group was completely reduced to a methyl group in 52% yield (Scheme 7). Apparently, electron transfer to the benzoate group is still possible however, the subsequent C–O bond cleavage does not

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• , HMQC, gs-HSQC, gs-HMBC, COSY, TOCSY, NOESY and NOE-difference spectroscopy. In compounds 4–7 the trifluoromethyl group exhibits very consistent chemical shifts, ranging from δ(F) −60.8 to −61.9 ppm. The fluorine resonance is split into a doublet by a small coupling (0.5–0.9 Hz) due to a through-space

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• ). Good regioselectivity (b/l: 81/19) was obtained with 2-buten-3-yl carbonate as a substrate (entry 14, Table 2). We conducted some control experiments to probe the effect of the bis(trifluoromethyl) group in the ligands (Scheme 3). With ferrocence-based biphenyl phosphine-oxazoline L2 as the ligand, the

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