Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• trifluoromethylation in a one-pot procedure with the Ruppert–Prakash reagent (Scheme 15, conditions III) [41]. The corresponding trifluoromethylselenylated (hetero)aryl products were obtained in moderate to good yields using both electron-deficient and -rich starting materials, respectively. Interestingly, the authors

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• products was assembled with moderate to high yields using this powerful synthetic strategy, and the scope of the reaction can be seen in Scheme 12. C–H trifluoromethylation The introduction of a CF3 group into pharmaceutical agents can enhance their performance in medicinal chemistry [129][130][131]. In

• catalyst. Proposed mechanism for the trifluoromethylation of 88. Plausible mechanism for the synthesis of substituted coumarins. Mechanism proposed for the phosphonylation reaction of 100. Plausible mechanism for the nitration of aniline derivatives via photoredox catalysis. Proposed mechanism for the

• purines via dual photoredox catalysis. Arylation of substituted arenes with an organic photoredox catalyst. C–H trifluoromethylation. Synthesis of benzo-3,4-coumarin derivatives. Oxidant-free oxidative phosphonylation. Nitration of anilines. Synthesis of carbazoles via intramolecular amination. Synthesis

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

• trifluoromethylation before 2011, and Besset [21] focused on the direct introduction of fluorinated groups into alkenes and alkynes. Then, Toste [1] covered advances in catalytic enantioselective fluorination, mono‑, di‑, and trifluoromethylation, and trifluoromethylthiolation reactions. Recently, Zhang [14] offered a

• 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

• . Trifluoromethylation Transition-metal-catalyzed trifluoromethylation reactions have made great progress in the joint efforts of organic fluorination scientists and metalorganic chemists over the past decade. Introducing trifluoromethyl groups into organic molecules can significantly alter their properties, such as

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• indicated that trifluoromethylation is an excellent tool for the detection of surface-bound materials by XPS. Keywords: chromophore; diaminoterephthalate; fluorine surface marker; fluorescence dye; lipoic acid; self-assembled monolayers; Introduction Diaminoterephthalates (DATs) are powerful fluorescence

• . The elemental compositions of these two SAMs were characterized by high-resolution XPS of the C 1s, O 1s, S 2p, N 1s and F 1s emissions. As is indicated by the high signal-to-noise ratio of the F 1s peaks, the trifluoromethylation is an excellent tool for the detection of surface-bound materials by

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• low yield of catalyst 4 may be due to steric bulkiness of the mesityl group that hampers close approach of d during coupling. For the synthesis of catalyst 6, the CF3 substituent was introduced to f by trifluoromethylation (Scheme 4). A racemic mixture of g was obtained after the TMS group was removed

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• -arylselanylnaphthaldehyde 25. In 2015, Shi and co-workers reported a novel and efficient method to construct CF3-substituted dihydronaphthalene derivatives 31 in moderate to excellent yields under mild conditions through the Cu(I)-catalyzed trifluoromethylation/ring-opening/cyclization of MCPs 1 with Togni reagent II (30

• oxidation and dehydrogenation gives the target product 49. A new and first achievement for the synthesis of CF3-contained seven-membered ring compounds 55 and 56 through trifluoromethylation of acrylamide-tethered alkylidenecyclopropanes 54 was presented by Shi and co-workers (Scheme 13) [78]. The possible

• trifluoromethylation of cyclopropanols 91 to construct β-trifluoromethyl-substituted ketones 106 (Scheme 23) [101]. Additionally, a series of cyclopropanols with different functional R groups were successfully scaled up to 1 mmol. In this transformation, there exist two possible pathways to produce the target product

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• obtained through isomerization with 1,2-migration of the ester groups. The B12-TiO2 hybrid catalyst can be regarded as a good alternative for conventional radical-involved organic syntheses using tin compounds. Recently, we discovered that the B12 derivative 1 can mediate trifluoromethylation and

• the presence of photosensitizers. 1,2-Migration of a phenyl group mediated by the visible-light-driven catalytic system composed of 1 and Irdfppy. Ring-expansion reactions mediated by the B12-TiO2 hybrid catalyst with UV-light irradiation. Trifluoromethylation and perfluoroalkylation of aromatic

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by ¹⁷O NMR spectroscopy

• Nico Santschi,
• Cody Ross Pitts,
• Benson J. Jelier and
• René Verel

Beilstein J. Org. Chem. 2018, 14, 2289–2294, doi:10.3762/bjoc.14.203

• structural elucidation technique to predict the constitution of an electrophilic iodine-based cyano-transfer reagent as an NC–I–O motif and study the acid-mediated activation of Togni's trifluoromethylation reagent. Keywords: electrophilic; hypervalent iodine; 17O NMR spectroscopy; trifluoromethylation

• ; trifluoromethylthiolation; Introduction The remarkable stability and reactivity of Togni's hypervalent iodine-based trifluoromethylation reagents (e.g., 4a) [1] have inspired the development of analogous compounds, including a well-known SCF3-transfer reagent 5 in 2013 by Shen and co-workers [2][3]. In the presence of

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• it a uniquely suited method for LSF. For example, Scaiano et al. have demonstrated the direct C–H trifluoromethylation of heterocycles using TMEDA, visible light from white LEDs, Methylene Blue as the photocatalyst and Togni’s reagent as the trifluoromethyl source (Scheme 26) [71]. The reaction is

• caffeine. The yields are good (44–92%), with regioselectivity being observed in a few cases. As with the trifluoromethylation by Pitre et al., this procedure does fit all the criteria for LSF, as it is very mild and simple, even though no complex structures are exemplified. Although it does not fit the

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

• reagents: CF3-benziodoxolone (Togni’s reagent) The ability to introduce the 2-iodobenzoic acid motif released from benziodoxolones has first been noticed by Ochiai in an isolated example of radical benzoyloxylation of THF [32], and by Gouverneur in the study of trifluoromethylation of allylsilanes [33

• ]. The use of this acid as an oxygen nucleophile, then, has been more fully investigated by the groups of Szabó and Sodeoka who have simultaneously described the copper-catalyzed benzoyloxy-trifluoromethylation of alkenes and alkynes using Togni’s reagent 5. The group of Szabó has first reported the use

• cyanotrifluoromethylation reaction. The mechanistic study of the oxy-trifluoromethylation of phenylacetylene has then led to demonstrate that the reaction is accelerated in the presence of additives such as B2pin2 [35]. A mechanism involving an initial step of transmetallation of B2pin2 with the Cu(I) catalyst was proposed

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

• -dimethyl-1,2-benziodoxole (1’, Figure 2), are effective and efficient hypervalent iodine reagents for trifluoromethylation reactions of a variety of substrates [22][23]. These reagents have found wide applications in the area of organofluorine chemistry, synthetic method development as well as medicinal

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• actively working in this direction for decades [12][13][16][17][18][19][20][21][22][23]. Our primary goal has been to develop fluorinating and fluoro-functionalized reagents for fluorination [18][19], trifluoromethylation [13][18][19], trifluoromethylthiolation [12][21] and pentafluoroarylation [22][23

• developed, including Shibata reagents I [20] and II [21] (trifluoromethylation reagent 1 and trifluoromethylthiolation reagent 2a, respectively), pentafluorophenylating reagent 2b and several hypervalent iodine reagents, i.e., diaryliodonium salts with a mesitylene ligand (3a–o) and a triisopropylphenyl

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

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

• good yields. Keywords: cyclization; fluorine; lactone; phthalide; trifluoromethylation; Introduction Phthalides (1(3H)-isobenzofuranones) are frequently found in natural products and exhibit a range of bioactivity (Scheme 1) [1][2]. Substituted phthalides have been used as building blocks for the

• 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

• the trifluoromethyl group (CF3) in biologically active molecules promote the development of novel methods to construct C–CF3 bonds in the past few years. Among the many methods developed, copper-catalyzed trifluoromethylation has gained enormous interest due to its high efficiency and cheapness

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

• ] from propargylic alcohol in ten steps, based on the trifluoromethylation key step of 1-(((E)-3-bromoallyloxy)methyl)benzene to obtain (E)-1-benzyloxy-4,4,4-trifluoro-2-butene. The sequence then involved Sharpless asymmetric dihydroxylation, nucleophilic opening of cyclic sulfate with NaN3, palladium

• a nucleophilic trifluoromethylation reaction of Ruppert’s reagent on the (R)-Garner’s aldehyde 5 in THF and in the presence of a catalytic amount of TBAF. Benzylation of the alcohol of 6 was then performed to obtain the desired intermediate as two diastereoisomers 7a and 7b that were easily

• demonstrating stronger extended conformational propensities. Interestingly, the conformation of the central residue gets more extended upon substitution of Ser (3JHN-Hα of 7.5 Hz) by the β-branched Thr residue (3JHN-Hα 8.4 Hz) and trifluoromethylation of Thr further stabilizes extended conformations (3JHN-Hα

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

• ; trifluoromethylation; trifluoromethylsulfenylation; trifluoromethylsufinylation; trifluoromethylsulfonylation; Introduction In the preceding paper, we described the various uses of sodium trifluoromethanesulfinate in direct trifluoromethylation, trifluoromethylsulfenylation, trifluoromethylsufinylation and

• review. The direct introduction of CF3S and CF3S(O) motifs also occupies a prime position in this review. 1 Trifluoromethylation Csp3–CF3 bond-forming reactions Trifluoromethylation of silyl enol ethers and enol acetates: After their original reports on the trifluoromethylation of aromatics in 1990 (Csp2

• –CF3 bond-forming reactions; see later in the text, Scheme 24) [6][7], Kamigata and co-workers studied silyl enol ethers in 1997 in trifluoromethylation reactions. Kamigata’s group reported that in the presence of RuCl2(PPh3)3, in benzene at 120 °C, silyl enol ethers could furnish the corresponding α

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

• widely used for the direct trifluoromethylation of a large range of substrates. Further, these two reagents are employed for the direct trifluoromethylsulfenylation and trifluoromethylsulfinylation, the introduction of the SCF3 and the S(O)CF3 group, respectively. In addition to the aforementioned

• reactions, the versatility of these two reagents is presented in other reactions such as sulfonylation and chlorination. This first part is dedicated to sodium trifluoromethanesulfinate. Keywords: fluorine; sulfur; trifluoromethylation; trifluoromethylsulfenylation; trifluoromethylsulfonylation

• popular nucleophilic trifluoromethylating reagent is certainly the trifluoromethyltrimethylsilane, CF3SiMe3, known as the Ruppert–Prakash reagent discovered in 1984 by Ruppert and applied for trifluoromethylation in 1989 by Prakash and Olah. More recently, renewed investigation on the use of fluoroform

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