Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• equiv of NaH in DCM under conditions similar to our previous reports on the deoxygenative trifluoromethylthiolation of carboxylic acids [31]. 19F NMR analysis of the crude reaction mixture after 2 h at rt revealed no conversion towards the desired acyl fluoride product 2a, however, 30% of thioester 3a

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• generation of carbene as a reactive intermediate [36][37]. Also, spirocyclic iodonium ylides have been used for radiolabeling techniques [38]. In 2013, Shibata’s research group reported a novel trifluoromethanesulfonyl iodonium ylide for trifluoromethylthiolation of enamines, indoles, and ketoesters

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• in the field have been interested in the design of original methodologies for the trifluoromethylthiolation and more recently the difluoromethylthiolation of various compounds by transition-metal catalysis [78]. Moreover, a recent interest was devoted to the trifluoromethylselenolation reaction as

• depicted in this section. I.1) Transition-metal-catalyzed C–H trifluoromethylthiolation of aromatic C(sp2) centers Thanks to its unique features such as an interesting lipophilicity (Hansch parameter = 1.44) [79][80] and a strong withdrawing character, the development of new methodologies for the

• -promoted trifluoromethylthiolation of benzamide derivatives 1 at the ortho-position by C–H bond activation [114]. Indeed, using a bidentate directing group (amide derived from the 8-aminoquinoline), the mono- and difunctionalized compounds were obtained when Cu(OAc)2 (0.5 equiv) and the toxic and volatile

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• functionalized pyridine and pyrrole derivatives from easily available 1,3-enynes. Therefore, the significant challenges will focus on the following aspects in the future: i) development of more functionalizations of pyridines and pyrroles (such as fluorination, trifluoromethylthiolation, olefination

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates

• approaches for the trifluoromethylthio (SCF3) difunctionalization of alkenes, such as cyanation [23], etherification [24][25][26][27], amination [28][29][30], chlorination [31][32], hydrogenation [33], trifluoromethylation [34], phosphonization [35], arylation [36][37][38], trifluoromethylthiolation [39

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• Ryouta Kawanishi Kosuke Nakada Kazutaka Shibatomi Department of Applied Chemistry and Life Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan 10.3762/bjoc.17.23 Abstract Decarboxylative trifluoromethylthiolation of lithium pyridylacetates was

• achieved using N-(trifluoromethylthio)benzenesulfonimide as the electrophilic trifluoromethylthiolation reagent. The reaction afforded the corresponding trifluoromethyl thioethers in good yield. Furthermore, the preparation of lithium pyridylacetates by saponification of the corresponding methyl esters and

• subsequent decarboxylative trifluoromethylthiolation were performed in a one-pot fashion. Keywords: decarboxylation; fluorinated compounds; pyridine compounds; trifluoromethylthiolation; Introduction The pyridine ring is found in numerous biologically active compounds. Therefore, efficient methods for

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• 2019, we reported a new reagent for nucleophilic trifluoromethylthiolation based on the benzothiazolium motif: BT-SCF3 [36][37][38]. This easily handled solid, which is stable at least over several months under ambient conditions, could be engaged in efficient deoxygenative trifluoromethylthiolation

• fluoride species, which can subsequently react with the alcohol, delivering thionoester 4. β-Fluoride elimination is a known decomposition pathway of −SCF3 and has even been exploited in synthetic trifluoromethylthiolation and fluorination processes [32][33][34]. The formation of the side-product 4a could

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• that trifluoromethanesulfenamides, electrophilic trifluoromethylthiolation reagents, could also perform nucleophilic trifluoromethylthiolations through the transient formation of a CF3SI species which presented an inverted polarity [49][50]. Based on a similar approach, we hypothesized that the CF3SeI

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• sulfonyl radical, prone to start a tandem sulfonylation/annulation of vinyl azides [84]. Recently, the phenanthridine core was assembled through a radical cascade triggered by the trifluoromethylthiolation of N-(o-cyanobiaryl)acrylamides. The process occurred under visible-light irradiation (6 W blue LED

• heteroarylalkynes. Synthesis of noravicine (14.2a) and nornitidine (14.2b) alkaloids. Gram-scale synthesis of the alkaloid trisphaeridine (15.3). Synthesis of phenanthridines starting from vinyl azides. Synthesis of pyrido[4,3,2-gh]phenanthridines 17.5a–d through the radical trifluoromethylthiolation of N-(o

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• cyclization to form a C-centered radical, which undergoes a trifluoromethylthiolation by •SCF3-radical-generated from AgSCF3 [133]. The iminoxyl radical 5-exo-trig cyclization step was confirmed in experiments with the capture of a C-centered radical by TEMPO. It should be noted that in the case of γ,δ

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Science, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China 10.3762/bjoc.16.62 Abstract A cascade oxidative trifluoromethylthiolation and cyclization

• involved in these transformations. Keywords: cyclization; indole derivatives; oxidation; radical reaction; trifluoromethylthiolation; Introduction The trifluoromethylthio (SCF3) group could significantly improve the lipophilicity of organic molecules as shown by its high Hansch constant (π = 1.44 for

• construction of compounds with structural diversity and complexity. In 2014, Wang reported the first radical cascade trifluoromethylthiolation and cyclization of activated alkenes (Scheme 1a) [23]. Afterward, Nevado [24], Hopkinson and Glorius [25], Dagousset and Magnier [26], as well as Fu [27] applied this

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

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

• to generate intermediate 38 which is oxidized by Cu(II) to provide the CF3-substituted dihydronaphthalenes derivatives 31 along with releasing a proton [65][66]. The trifluoromethylthiolation of MCPs 1 with AgSCF3 was achieved by Shi et al. which proceeds through a sequence of radical addition, ring

• copper-catalyzed ring-opening and trifluoromethylation or trifluoromethylthiolation of cyclopropanols 91 for the synthesis of β-CF3/SCF3-substituted ketones 113 (Scheme 24) [102]. This strategy was also applied to the synthesis of LY2409021. The LY2409021 was a glucagon receptor antagonist and used in

• diethyl phosphites. Organic-selenium induced radical ring-opening and cyclization of MCPs derivatives (cyclopropylaldehydes). Copper(I)-catalyzed oxidative radical trifluoromethylation/ring-opening/cyclization of MCPs with Togni reagent II. Ag(I)-mediated trifluoromethylthiolation/ring-opening/cyclization

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

• ; 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

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

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

• atom is retained for trifluoromethylsulfenylation (also named trifluoromethylthiolation), trifluoromethylsulfinylation, or trifluoromethylsulfonylation reactions. Typically, CF3SO2Na reacts under oxidative conditions whereas CF3SO2Cl requires reductive conditions. The advent of a new dynamism and the

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• alkaloid-based organocatalysts to carry out the α-trifluoromethylthiolation of β-ketoesters 1 by using the hypervalent iodine-based CF3S-transfer reagent 36 in an asymmetric fashion. Very interestingly, they realized that for indanone-based ketoesters 1 (with n = 1) simple cinchona alkaloids themselves

• dearomatization of phenols and naphthols. Ishihara’s ammonium salt-catalysed oxidative cycloetherification. Chiral phase-transfer-catalysed α-sulfanylation reactions. Chiral phase-transfer-catalysed α-trifluoromethylthiolation of β-ketoesters 1. Chiral phase-transfer-catalysed α-amination of β-ketoesters 1 using

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• [18][19], decarboxylative alkenylation of cycloalkanes with aryl vinylic carboxylic acids [20][21], trifluoromethylthiolation [22], thiolation [23][24], alkenylation [25][26], dehydrogenation−olefination and esterification [27][28], radical addition/1,2-aryl migration [29], cascade alkylation

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

• ]. In the same paper, the authors showed that cobalt perchlorate could also improve the yield of the uncatalyzed reaction. Iron sulfate, on the other hand, gave the same yield as in the absence of added metals. 4 Catalytic trifluoromethylthiolation Aryl trifluoromethyl sulfides (ArSCF3) play an

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

• 10.3762/bjoc.9.270 Abstract The CF3SN moiety is a substituent with interesting properties. However, there is no easy synthetic access to molecules bearing this group. The trifluoromethanesulfenamide is a new reagent for the electrophilic trifluoromethylthiolation which reacts easily with amines to obtain

• trifluoromethylsulfanylamines with good yields. Keywords: amine; fluorine; organo-fluorine; trifluoromethanesulfenamide; trifluoromethylsulfanylamine; trifluoromethylthiolation; Introduction In past decades, fluorinated molecules have found more and more applications in a variety of fields, especially in the design of new

• panel of trifluoromethylsulfanylamines. The trifluoromethanesulfenamide 1a is an efficient reagent for the electrophilic trifluoromethylthiolation of carbon nucleophiles [38][39][40][41][42][43][44]. Therefore, this reagent should react with amines to perform transamination reactions with secondary