Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• -trifluoromethyl compound. The benzoyloxy-trifluoromethylation of dienes has also been reported with CuCN as the catalyst. The reaction, again, is selective with respect to the olefin geometry – (E)-alkenes are exclusively obtained – and the regioselectivity – products resulting from a sterically-controlled 1,4

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• OLEDs. In fact, Wang and collaborators reported a red-emitting device based on Pt(fppz)2 [39], where fppz is 3-(trifluoromethyl)-5-(2-pyridyl)-1H-pyrazolate, that attained remarkable EQE of 31% [40] (see Figure 7 for the chemical structure of the complex). With the aim of correlating molecular structure

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• (PhIO)-mediated intramolecular azirination in a one-pot process. Keywords: azirination; 2H-azirine; iodosobenzene; Togni reagent; β-trifluoromethylation; Introduction The trifluoromethyl group is a striking structural motif, which can be widely found in the fields of pharmaceutical and agrochemical

• CF3 group into various organic molecules, the further development of novel routes for the selective trifluoromethylation is of continuing interest for synthetic and medicinal chemists. Togni reagents, including 1-(trifluoromethyl)-1,2-benziodoxol-3(1H)-one (1) and trifluoromethyl-1,3-dihydro-3,3

• trifluoromethylation and azirination reaction. As shown in Scheme 3, a variety of substrates bearing halogen substituents at the ortho, meta and para-positions of the phenyl ring in the substrates were converted to the expected 2H-azirines 7b–e in 45–65% one-pot yield. Notably, the substrate having a trifluoromethyl

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• -trifluoromethylbenzyl bromide [14]. Quinine was reacted with 4-trifluoromethylbenzyl bromide or 3,5-bis(trifluoromethyl)benzyl bromide to obtain C16 or C17. In the beginning, the alkylation of 2 in the catalysis of C1 in the two-phase system (toluene and 50% NaOH aqueous solution) was tested, although the yield was

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• (4k and 4l), trifluoromethyl (4m), cyano (4n), and ester (4o) substituents at the para-position of the phenyl ring were successfully used in the reaction, giving rise to the desired coupling products in good yields (47–79%). The homoallylic alcohols 4p–t were formed with a high degree of syn

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• regioselectivity for the C-6 position of bipyridinones and the C-8 position of quinoline N-oxides and tolerated a broad range of functionalities, such as halogens, ethers, or trifluoromethyl groups. Keywords: C–H activation; hypervalent iodine; indoleBX; indoles; pyridinones; rhodium catalysis; Introduction

• not be used as directing group (5e), confirming what has already been reported by others authors [13]. Quinoline 7f was obtained in 79% yield. Concerning the pyridinone core, both an electron-donating methyl group and electron-withdrawing trifluoromethyl and fluoro groups (7g–i) were well tolerated in

• the C-3 position. However, the strong electron-withdrawing CF3 group resulted in a lower 65% yield (7h). This observation is also true for the C-4 position. Indeed, products 7j–l were synthesized in 78% yield for a methyl, 66% yield for a trifluoromethyl and 84% yield for a benzyloxy substituent. As

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• derivative of iodosodilactone 6-(3,5-bis(trifluoromethyl)phenyl)-1H,4H-2aλ3-ioda-2,3-dioxacyclopenta[hi]indene-1,4-dione (abbreviated as FPID, Figure 1) [29]. In combination with tris(4-methoxyphenyl)phosphine [(4-MeOC6H4)3P], FPID can efficiently mediate peptide coupling reactions within 30 minutes to

One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone–sulfuric acid

• Natalia Soldatova,
• Pavel Postnikov,
• Olga Kukurina,
• Viktor V. Zhdankin,
• Akira Yoshimura,
• Thomas Wirth and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 849–855, doi:10.3762/bjoc.14.70

• –m in lower yields. Similar reactions of 3,5-bis(trifluoromethyl)iodobenzene (1d) with benzene and mesitylene formed the corresponding iodonium salts 3n and 3o in moderate yields. With electron-deficient arenes 2 such as chlorobenzene (2e) and benzene, an excess of sulfuric acid and arene was used to

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• reactivity pattern that differs from the related reagents TolIF2, PhI(OH)OTs or PhI(NTs2)2 (Scheme 1b and c). With 1b, however, the reactions were entirely selective for 2,3-dichlorination of the allene, which was consistent with the regiochemical outcome of reactions involving a trifluoromethyl radical

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• [1][2]. Therefore, the development of novel synthetic methods for the introduction of fluorinated fragments, such as trifluoromethyl (CF3), difluoromethyl (CF2H), and difluoromethylene (-CF2-), has attracted a great deal of attention from synthetic organic chemists [3][4][5][6]. Among these methods

• , many researchers including us have studied the catalytic asymmetric synthesis of optically active α-trifluoromethylated tertiary alcohols [7][8]. In these cases, one of commercially available and versatile trifluoromethyl sources, trifluoropyruvate, has been utilized for a variety of catalytic

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• mixture stirred for 30 min. The precipitate was isolated and dried overnight. The product was purified by recrystallization from toluene. 4-Fluoro-N-((trifluoromethyl)sulfonyl)benzamide (9a) [9]: Synthesized by general procedure. The product was obtained as small clear crystalline flakes (1.88 g, 69%). mp

• (s, 3F), −105.75 (s, 1F); HRMS (TOF) m/z: [M − H]− calcd for C8H4F4NO3S−, 269.9854; found, 269.9888. 4-Trifluoromethyl-N-((trifluoromethyl)sulfonyl)benzamide (9b): Synthesized by general procedure. The product was obtained as white powder (2.83 g, 88%). mp 174–179 °C; 1H NMR (500 MHz, methanol-d4) δ

• C9H4F6NO3S−, 319.9822; found, 319.9869. Pentafluoro-N-((trifluoromethyl)sulfonyl)benzamide (9c): Synthesized by general procedure. The product was obtained as clear needle-shaped crystal (2.40 g, 70%). mp 129–131°C; 13C NMR (126 MHz, methanol-d4) δ 158.6, 145.4 (dm, J = 257.0 Hz), 144.5 (dm, J = 256.8 Hz

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• highly selective reaction conditions could be developed in parallel with the progress in understanding the mechanism of these transformations [6][7][8][9]. Also, aldol reactions with fluorinated substrates, particularly with trifluoromethyl-containing ones, were investigated [10][11][12][13]. In recent

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

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• addition–cyclization reactions of aryl 2-alkynoates with RC(=O)CO2H/AgNO3(cat.)/K2S2O8 at 60 °C [24], with Cu(OAc)2/1-trifluoromethyl-3,3-dimethyl-1,2-benziodoxole (Togni reagent) at 60 °C [25], with R2P(=O)H/Ag2CO3(cat.)/Mg(NO3)2 at 100 °C [26], with BrCF2CO2Et/fac-Ir(ppy)3(cat.) under irradiation at rt

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• total synthesis. In 2013, Grellepois described the synthesis of chiral β-aryl(alkyl) β-trifluoromethyl β-amino esters 23a–o based on the highly diastereoselective zinc-mediated addition of Reformatsky reagents, in situ generated by treatment of bromoesters 9a–d by Zn in the presence of CuCl in 2-Me-THF

• , to chiral α-aryl(alkyl) α-trifluoromethyl N-tert-butylsulfinyl hemiaminals 24a–g, constituting bench-stable surrogates of trifluoromethyl ketoimines [26]. As illustrated in Scheme 9, a range of these chiral aza-Reformatsky products 23a–o were obtained in moderate to high yields (57–87%) combined with

• moderate to excellent diastereoselectivities (64–98% de). The best diastereoselectivity (>98% de) was achieved in the formation of β-alkyl β-trifluoromethyl β-amino esters 23k–o (R1 = Me or Et) while moderate to high diastereoselectivities (64–92% de) were obtained for the synthesis of β-aryl β

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• reactions involving sulfonium and sulfoxonium ylides have been reported recently [26][27][28][29][30][31][32]. For example, Shen and co-workers reported the use of trifluoromethyl-substituted sulfonium ylide 5 in electrophilic trifluoromethylation reactions [33][34]. Moreover, Maulide and co-workers

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• convenient regioselective synthetic methods with mild conditions and good yields of the reactions [40][41]. Aggarwal et al. [42] reported the regiospecific synthesis of 4-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines 18 by the reaction of 5-aminopyrazole 16 with trifluoromethyl-β-diketones 17 in refluxing

• have been confirmed unambiguously by HMBC, HMQC and 19F NMR studies. The authors proposed that trifluoromethyl-β-diketone exists mainly in keto form 17 under solvent-free conditions whereas under solvent-mediated conditions the enolic form 21 towards the carbonyl carbon that carries the CF3 group is

• predominant. The keto form 17 results in the formation of 6-trifluoromethylpyrazolo[3,4-b]pyridines 20 by attack of the 5-NH2 group (from 5-aminopyrazole 16) on the more electrophilic carbonyl group attached to CF3 (from trifluoromethyl-β-diketones 17) whereas the enolic form 21 reacts with the less

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• been few reports on the preparation of fluoroalkyl phthalides [11][12][13][14][15][16][17][18][19]. The first synthesis of 3-(trifluoromethyl)phthalides was accomplished by Reinecke and Chen in 1993. They studied ortho-lithiation of phenyloxazolines and the subsequent reactions with pentafluoroacetone

• and hexafluoroacetone to give 3-(trifluoromethyl)phthalide derivatives [11]. In 2006, Pedrosa et al. reported the nucleophilic trifluoromethylation of protected ortho-phthalaldehyde, followed by deprotection and oxidation to afford 3-(trifluoromethyl)phthalide [12]. Pohmakotr et al. demonstrated the

• nucleophilic trifluoromethylation of acid anhydrides to produce γ-hydroxy-γ-trifluoromethyl-γ-butyrolactones, which acted as good precursors in the synthesis of γ-trifluoromethyl-γ-butyrolactones with organometallic reagents [16]. All these protocols involve multiple steps to obtain trifluoromethylphthalides

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• trifluoromethyl groups into organic molecules has attracted great attention in the past five years. In this review, we describe the recent efforts in the development of trifluoromethylation via copper catalysis using nucleophilic, electrophilic or radical trifluoromethylation reagents. Keywords: copper; fluorine

• ; trifluoromethylation; Introduction The fluorine atom has a strong electronegativity and a small atomic radius, and the incorporation of fluoroalkyl groups into molecules imparts a variety of features. The trifluoromethyl group, as the most significant common used fluoroalkyl group, could improve molecular properties

• such as metabolic stability, lipophilicity and permeability [1][2][3][4]. Therefore, organic molecules bearing trifluoromethyl groups are widely used in pharmaceuticals and agrochemicals, such as the antidepressant fluoxetine, the anti-ulcer drug lansoprazole and so on (Figure 1). The specific roles of

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• form an aryl radical. This reactive intermediate reacts with the anion of the respective thiol to form the corresponding diaryl sulfide adducts. The reaction conditions tolerate functional groups like alcohols, esters, halides, the trifluoromethyl group and heterocyclic substrates like thiazoles or

• production could only be achieved by careful selection and adjustment of the type and amount of basic additives. The scope of this method includes electron-rich and electron-deficient 2-aryl-substituted benzothiophenes. However, strongly electron-donating methoxy or electron-withdrawing trifluoromethyl

• , trifluoromethyl groups and halides, but iodides led to polymer formation. Li and Wang developed a method for the α-C(sp3)–H thiolation of ethers, using Acridine Red as photosensitizer and tert-butyl hydroperoxide (TBHP) as oxidant (Scheme 38) [73]. They reported that photoexcited Acridine Red performs an energy

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• atoms (connected directly to the chromophore or as side groups) on the molar absorptivity and the fluorescence intensity of a series of new TO analogues. Photophysical properties of a series of TO analogues that have fluoro- or trifluoromethyl groups connected to the heterocyclic end groups of the

• than TO under the same conditions (Table 1). In contrast, the dyes bearing trifluoromethyl groups in the 7 position of the quinoline moiety show weak emission even in presence of host molecules. This can be attributed to the strong electron-withdrawing effect of the CF3 group, which change the pathways

• filtered off and dried in a desiccator. Yield: 97%. The compound is hygroscopic and unstable and its chemical structure was confirmed from the structures of the final dyes. 1-Benzyl-4-chloro-7-(trifluoromethyl)quinolinium bromide (4c) 4-Chloro-7-(trifluoromethyl)quinoline (3b, 1 mmol) and benzyl bromide

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

• observed for the central residue upon replacement of Ser by the β-branched Thr residue and the incorporation of a trifluoromethyl group in Thr or allo-Thr further increases the β-propensity of these residues. The presence of self-association involving intermolecular β-sheet formation was not detectable

• which have higher propensities to form compact α-helix-like conformations. All together, the theoretical study shows that the replacement of the methyl group of the threonine side chain in the RNH-Ala-Val-Thr-Val-Leu-OMe pentapeptide by a trifluoromethyl induces an increase of the population of global

• the pentapeptides on this process. The objective of this preliminary study was to analyze the influence of the trifluoromethyl group and of the propensity of the pentapeptides to adopt an extended structure, on their ability to modulate Aβ1-42 peptide aggregation. For that purpose, the classical

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

• , regenerating the trifluoromethyl radical in the process, was also considered. Intermediate 2 was ultimately converted into the final product after liberating an acetyl cation, which was captured by a chloride anion to give acetyl chloride (Scheme 3). Trifluoromethylation of olefins with cascade reactions: The

• was obtained predominantly: the α-aryl-β-trifluoromethyl amide 6. This compound was determined to be issued from a trifluoromethylation/1,4-aryl shift/desulfonylation cascade reaction (Scheme 7). This reaction could be performed on various N-aryl,N-tosylacrylamides with moderate to good yields. The

• shown that the reaction proceeded equally smoothly when using BiOBr nanosheets catalysis [14]. The proposed mechanism of these two reactions is represented in Scheme 8. Alongside the classical pathway, the trifluoromethyl radical was generated and added onto the N-tosylacrylamide. The obtained radical

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

• ; 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

• group imparts enhanced lipophilicity of aromatic compounds in comparison with aryl–CF3 analogues (Hansch’s hydrophobic parameter π(SCF3) = 1.44; π(OCF3) = 1.04 versus π(CF3) = 0.88). Trifluoromethyl sources are manifold displaying nucleophilic, electrophilic or radical reactivities [11]. The most

• , CF3H, as an ideal source of trifluoromethide offered new horizons for atom-economical, low-cost trifluoromethylation reactions. With regard to electrophilic CF3 donors, S-(trifluoromethyl)sulfonium salts developed by Yagupolskii and Umemoto and hypervalent iodine(III)-CF3 reagents developed by Togni