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

• rotation are in reasonable agreement with the experiments. Keywords: dithiocarbamates; electrophilic trifluoromethylation; Togni reagents; Introduction Dithiocarbamates are well known for their manifold applications as pesticides, fungicides and crop protection agents in agriculture [1][2][3], as

• 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

• ) have been used extensively in trifluoromethylations of S-, P-, O-, and C-nucleophilic functionalities [25][26][27][28][29][30][31][32]. Although reports exist on the synthesis of fluorinated dithiocarbamates [33][34][35], the direct trifluoromethylation of dithiocarbamates has not been described. In

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

• employed directly or generated in situ from precursors by published reports. Relative reactivities were also found to highly dependent on the nature of the iodoarenes. Keywords: benchmarking; copper; fluorine; fluoroalkylation; trifluoromethylation; Introduction Selectively fluorinated molecules that

• seen rapid growth in the past ten years. Copper is one of the most successfully used metals for mediating the trifluoromethylation of aryl halides, and the active form of the reagents is typically a copper(I) complex bearing a trifluoromethyl ligand, i.e., [LnCu–CF3]. Sporadic examples of

• trifluoromethylation ‘catalysis’ using copper have been observed [4][5][6][7][8][9], but these reactions typically only work for aryl iodides and have a low substrate scope, low turn-over values, and/or involve decarboxylation reactions at high temperatures. Stoichiometric trifluoromethylating agents are therefore

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• residence time. Noël optimized, for the first time, a trifluoromethylation of aromatic heterocycles by continuous-flow photoredox catalysis. The process benefited from the use of microreactor technology and readily available photocatalysts. The process was also employable for perfluoroalkylation. The

• . Trifluoromethylation by continuous-flow photoredox catalysis. Flow photochemical synthesis of 6(5H)-phenanthridiones from 2-chlorobenzamides. Synthesis of biaryls 14a–g under photochemical flow conditions. Flow oxidation of hydrazones to diazo compounds. Synthetic use of flow-generated diazo compounds. Ley’s flow

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

• fluoroalkylated aromatics. Keywords: β-carbon elimination; carbon–carbon bond cleavage; decarboxylation; tetrahedral intermediate; trifluoroacetate; fluoral; trifluoromethylation; Introduction Organofluorine compounds attract attention because of their applicability in various fields, such as medicine

• − source and [CF3Cu] species with CuI are generated in situ. In the presence of CuI, CF3CO2Na undergoes trifluoromethylation with aryl halides via decarboxylation [33][34] (Scheme 1). A pentafluoroethyl group (C2F5) was fixed at the arene with sodium pentafluoropropionate [35] (Scheme 2). The reaction

• synthesis of 2,2-difluorostyrenes through Mg(0)-promoted defluorinative silylation followed by fluorine-ion-catalyzed 1,2-desilylative defluorination. Buchwald et al. demonstrated aromatic trifluoromethylation using potassium trifluoroacetate (CF3CO2K), CuI and pyridine under flow conditions. Increasing the

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• trifluoromethylation reagents, which found many practical applications [3]. I respect him for his persistent passion for science. Even at the age of 86 in 2015, he still goes to his office and advises his students and remains active in the field of fluorine chemistry. I received my Ph.D. degree in December of 1992. My

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• ), in which the transition metal is omitted, relied on the trifluoromethylation of isonitriles to yield trifluoromethylphenanthridines (Scheme 7) [21]. This approach employed the Togni reagent, and Bu4NI was applied as radical initiator; whereby phenanthridines were prepared in good to excellent yields

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

• used without further purification. Subsequently, trifluoromethylation provided the ligands L1a–d in moderate yields, upon treatment with Ruppert’s reagent (TMSCF3) and CsF [42][43][44][45]. Notably, ligands L1a–d are moisture and air-stable, and their NMR spectra show no change even after being stored

Direct C–H trifluoromethylation of di- and trisubstituted alkenes by photoredox catalysis

• Ren Tomita,
• Yusuke Yasu,
• Takashi Koike and
• Munetaka Akita

Beilstein J. Org. Chem. 2014, 10, 1099–1106, doi:10.3762/bjoc.10.108

• CF3-substituted alkenes via direct Calkenyl–H trifluoromethylation. 1,1-Di- and trisubstituted alkenes were applicable to this photocatalytic system, providing the corresponding multisubstituted CF3-alkenes. In addition, use of an excess amount of the CF3 source induced double C–H trifluoromethylation

• to afford geminal bis(trifluoromethyl)alkenes. Conclusion: A range of multisubstituted CF3-alkenes are easily accessible by photoredox-catalyzed direct C–H trifluoromethylation of alkenes under mild reaction conditions. In particular, trifluoromethylation of triphenylethene derivatives, from which

• synthetically valuable tetrasubstituted CF3-alkenes are obtained, have never been reported so far. Remarkably, the present facile and straightforward protocol is extended to double trifluoromethylation of alkenes. Keywords: electrophilic trifluoromethylating reagent; multi-substituted alkene; photoredox

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

• trifluoromethylation; 19F NMR kinetics; nitration; organo-fluorine; Introduction Since the advent of the hypervalent-iodine-based electrophilic trifluoromethylation reagents 1 and 2 in 2006 they have found widespread application in organic synthesis (Figure 1) [1][2][3][4]. Recently, increasing interest has been

• directed towards the photocatalytic one-electron reduction of these compounds in order to generate the highly electrophilic trifluoromethyl radical [5][6][7]. For example, Gouverneur et al. have highlighted the regioselective allylic trifluoromethylation employing reagent 2, [Ru(bpy)3]Cl2 and allylsilanes

Cu-Mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF₃

• Xueliang Jiang and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2013, 9, 2862–2865, doi:10.3762/bjoc.9.322

• 201620, China 10.3762/bjoc.9.322 Abstract A Cu-mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF3 was developed for the first time. This method offers a convenient and economical approach to various trifluoroethyl-containing compounds. Keywords: copper

• ; methanesulfonates; organo-fluorine; trifluoromethylation; Introduction Fluorinated organic molecules are extremely important in agrochemicals, pharmaceuticals and materials [1][2][3][4][5][6]. In recent years, (trifluoroethyl)arenes have drawn increasing attention in medicinal chemistry and related fields [7][8][9

• -mediated trifluoroethylation of arylboronic acids [13][14] (Scheme 1a) and trifluoromethylation of benzyl halides [15][16][17][18][19][20][21] (Scheme 1b) are more convenient. Especially trifluoromethylations of benzyl bromides with a [CuCF3] species, which are generated from different precursors, are

The renaissance of organic radical chemistry – deja vu all over again

• Corey R. J. Stephenson,
• Armido Studer and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 2778–2780, doi:10.3762/bjoc.9.312

• ][14][15][16], e) radical trifluoromethylation [17] and radical fluorination [18][19][20], f) natural product synthesis [21], g) new main group radical chemistry involving elements like boron [22], phosphorous [23] and selenium [24], tellurium [25], among others, h) synthesis or functionalization of

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• possibilities in the future of drug development. To date, the introduction of fluorine into medicinal entities [1][2] has mostly taken the form of aryl fluorination [3][4] or trifluoromethylation [5][6], and fascinating developments in synthetic methodology of this type are continuing to occur [7][8][9

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

• , Hengyang, Hunan 421001, China 10.3762/bjoc.9.299 Abstract An efficient method for the copper-catalyzed trifluoromethylation of terminal alkenes with an electrophilic trifluoromethylating reagent has been developed. The reactions proceeded smoothly to give trifluoromethylated alkenes in good to excellent

• 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

• pharmaceutically and agrochemically relevant molecules usually enhances their chemical and metabolic stability, lipophilicity and binding selectivity [1][2][3][4][5][6][7]. As a result, considerable effort has been directed towards the development of efficient and versatile trifluoromethylation methods [8][9][10

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

• -fluorine; transition metal; trifluoromethylation; trifluoromethylthiolation; Review Introduction The incorporation of fluorine or fluorinated moieties into organic compounds plays a key role in Life-Science oriented research as often-profound changes of the physico-chemical and biological properties can

• trifluoromethylation reactions [22][23][24][25][26][27][28]. The present review focuses on fundamental achievements in the field of transition metal-catalyzed mono-, di- and trifluoromethylation as well as trifluoromethylthiolation of sp² carbon atoms. We present the different developments according to the reaction

• trifluoromethylation of aromatic compounds has been extensively reviewed in recent years by several authors [23][24][25][26][27][28][63][64]. Nevertheless, aromatic trifluoromethylations catalytic in metal are still rare. This section reviews recent advances in this area and classifies the reactions according to metal

Oxidative 3,3,3-trifluoropropylation of arylaldehydes

• Akari Ikeda,
• Masaaki Omote,
• Shiho Nomura,
• Miyuu Tanaka,
• Atsushi Tarui,
• Kazuyuki Sato and
• Akira Ando

Beilstein J. Org. Chem. 2013, 9, 2417–2421, doi:10.3762/bjoc.9.279

• , agricultural chemicals, and functional materials because trifluoromethylation of such chemicals often significantly improves their performance [1][2][3][4][5][6]. To date, the trifluoromethylation of carbonyl compounds [7][8][9][10] and aryl halides [11][12][13] has been extensively explored. On the other hand

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

• The trifluoromethylation of aryl iodides catalyzed by copper(I) salt with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide and Zn dust was accomplished. The catalytic reactions proceeded under mild reaction conditions, providing the corresponding aromatic trifluoromethylated

• . Keywords: organo-fluorine; Ruppert–Prakash reagent; trifluoromethyl; trifluoromethylation; trifluoromethyl zinc; Introduction Organo-fluorine compounds have received considerable attention in the fields of biomedical chemistry, agrochemistry, and organic material science due to their unique chemical

• [7]. As a result, trifluoromethylated compounds have been efficiently synthesized by both building-block methods which employ trifluoromethylated substrates and direct methods which employ trifluoromethyl reagents [7][8][9]. However, a nucleophilic trifluoromethylation by trifluoromethyl

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• Satoshi Okusu Yutaka Sugita Etsuko Tokunaga Norio Shibata Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan 10.3762/bjoc.9.257 Abstract Regioselective conjugate 1,4-trifluoromethylation of α,β-unsaturated

• yields. Keywords: 1,4-addition; copper; fluorine; Michael addition; organo-fluorine; trifluoromethylation; Introduction One of the challenges in synthetic organic chemistry is the nucleophilic 1,4-addition of the trifluoromethyl (CF3) group into electron-deficient internal alkenes as represented by the

• Michael addition reaction, even in a racemic, non-stereoselective fashion [1][2][3][4][5]. The nucleophilic trifluoromethylation to conjugated alkenes essentially occurs solely via a 1,2-addition [1][2][3][4][5][6][7][8][9][10][11], not a 1,4-addition (Scheme 1), with the exception of non-general examples

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• helical assemblies, these two properties were examined for L-5-F3Ile, as one of the possible fluorinated analogues of proteinogenic isoleucine. Results and Discussion Amino acid synthesis We have recently described a new method for the conjugate trifluoromethylation of α,β-unsaturated acyloxazolidinones

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

• Lin Yan,
• Zhiqiang Han,
• Bo Zhu,
• Caiyun Yang,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2013, 9, 1853–1857, doi:10.3762/bjoc.9.216

• introduce a CF3 group, Shibata and co-workers [13] and Jiang and co-workers [14] successively reported the asymmetric allylic trifluoromethylation of MBH adducts with Ruppert’s reagent [(trifluoromethyl)trimethylsilane, Me3SiCF3] in the presence of (DHQD)2PHAL as catalyst. In 2011, our research group [15

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• Synthesis of axially chiral ligands Initially, we attempted to synthesize the desired axially chiral ligands 7, and the synthetic route is shown in Scheme 1. Using methyl 1-hydroxy-2-naphthoate (9) as the starting material, trifluoromethylation with Tf2O in the presence of pyridine afforded its

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

• ][31][32], the trifluoromethylthio anion [29] or electrophilic perfluoroalkylating agents [33]. Others are devoted to particular methods such as trifluoromethylation initiated by sodium dithionite [34] or the electrochemical introduction of fluoroalkyl groups in organic molecules [35]. Moreover, many

• (B), (C) and (D) are produced as a consequence of loss of chloride from the intermediate radical anion as shown in Scheme 42. Such side reactions explain the decrease of trifluoromethylation efficiency with the number of thiol groups present in a series of thiolated chlorobenzenes. The yields are 72

• presumably as the result of photo-substitution of chlorine in 4-trifluoromethylsulfanylchorobenzene by an SRN1 mechanism. HMPA suppressed this side-reaction (similar to iodobenzene with potassium diethyl phosphite [180]) and promoted trifluoromethylation (Table 6). The reaction solvent is important and the

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

• /bjoc.6.65 Abstract Since the discovery by Yagupolskii and co-workers that S-trifluoromethyl diarylsulfonium salts are effective for the trifluoromethylation of thiophenolates, the design and synthesis of electrophilic trifluoromethylating reagents have been extensively researched in both academia and

• this field is in constant development. Keywords: asymmetric synthesis; electrophilic; fluorine; reagent; trifluoromethylation; Review The chemistry of fluoro-organic compounds is one of the areas of the life sciences that have developed most rapidly over the last 50 years, despite the fact that

• ]. Among the increasingly powerful methods that have been developed for the direct introduction of fluorine into organic compounds, trifluoromethylation is one of the most direct and straightforward strategies in the synthesis of fluorine-containing organic compounds. Efficient transfer of the

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

• recently in detail on the preparation of O-(trifluoromethyl)dibenzofuranium salts 4 [28][29][30][31] and their use as CF3-transfer agents based on studies of Yagupol'skii [32]. The direct O- and N-trifluoromethylation of alcohols, phenols, amines, anilines and pyridines under mild conditions was described

• scale. Togni managed very recently to circumvent these difficulties by using hypervalent iodine compounds such as 5 [33][34][35]. When 2,4,6-trimethylphenol was treated with the hypervalent iodine compound depicted below, the corresponding trifluoromethyl ether was obtained beside C-trifluoromethylation