Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• + absorbing at 740 nm in a the photocatalyzed trifluoromethylation reaction of 5 into 8 proposed by the same authors (Figure 2) [19]. These latter have shown the benefits of using their system based on an irradiation with red-light and the osmium complex over the ruthenium one with blue-light in a large-scale

• emerged as potent catalysts for red-light-mediated photoreactions. Furuyama et al. demonstrated that a ruthenium phthalocyanin complex could catalyze trifluoromethylation reactions of styrene derivatives 18 with either CF3SO2Cl or Umemoto’s reagent 19 under red-light irradiation without the need for

• redox properties similar to those of squaraine derivatives, enabling key transformations such as the cyclization of anilines with maleimides and the reduction of Umemoto salts for trifluoromethylation of alkenes. With an excited-state reduction potential around 0.80 V, 46 demonstrates the capability to

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• -butoxy radical C, which can abstract the hydrogen atom from TBHP to form tert-butylperoxy radical B. The alternative pathway for the formation of radical B is the oxidation of TBHP with complex A. A manganese-catalyzed radical approach for the remote trifluoromethylation–peroxidation of non-activated

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• involved a Mn(II)/Mn(III) cycle at the anode, which differs from Ackermann’s reported Mn(III)/Mn(IV) cycle at the anode (Scheme 46). A photoelectrochemistry method for the C–H trifluoromethylation of arenes using the Langlois trifluoromethylation reagent (CF3SO2Na) was developed by Ackermann and coworkers

• [70]. The mildness of this reaction was demonstrated through the late-stage C–H trifluoromethylation of ascapheine, pentoxifylline, doxophylline, theobromine, methylethrone, and tryptophan derivatives. During the reaction, irradiation of the organic dye Mes-Acr+ leads to the formation of its oxidized

• disclosed a similar trifluoromethylation of arenes under photoelectrochemical reaction conditions but without the addition of a photocatalyst, using trifluoroacetic acid as the CF3 source (Scheme 47b) [71]. This alternative approach further underscores the versatility and applicability of

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• available in the absence of Lewis acid activation (Scheme 1a) [11][12]. A variety of Lewis acid activators have been reported [13][14][15][16][17][18][19][20][21][22] in an array of group-transfer reactions, including trifluoromethylation, cyanation, and fluorination. Brønsted acid activation has also been

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• fluorobenziodoxole, are also utilized as F+ equivalents to introduce fluorine atoms into organic molecules. In addition, various trifluoromethylation reagents have been developed so far [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Transition-metal-catalyzed fluorination and trifluoromethylation methods have

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• , heteroromatic aldehyde-derived hydrazones as well as heteroaromatic sodium sulfinate salts were additional compatible reagents [75]. In 2022, Xie et al. achieved the electrochemical C(sp2)–H trifluoromethylation of (hetero)aromatic aldehyde-derived hydrazones. The galvanostatic electrolysis was performed with

• aldehyde-derived hydrazones [70]. Azolation of aldehyde-derived hydrazones [72]. Thiocyanation of benzaldehyde-derived hydrazone 122 [73]. Sulfonylation of aromatic aldehyde-derived hydrazones [74]. Trifluoromethylation of aromatic aldehyde-derived hydrazones [76]. Electrooxidation of benzophenone

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , epiandrosterone, hecogenin, rockogenin, and tigogenin. All of them were successfully converted into boronic esters with high diastereoselectivity. In 2021, Cook and co-workers [45] unveiled the photomediated trifluoromethylation of alcohols by converting alcohols into thiocarbonates (Scheme 8). This copper

• -mediated deoxygenative trifluoromethylation technique worked with both benzylic and unactivated thiocarbonates. The proposed mechanism starts with the homolysis of (bpy)Cu(III)(CF3)3 by blue-light irradiation, which produces CF3 radicals and (bpy)Cu(II)(CF3)2. Subsequently, the interaction between the CF3

• radical and silane furnishes a Si-based radical, which in turn reacts with the thiocarbonate to form an alkyl radical. Finally, a coupling reaction of the alkyl radical with (bpy)Cu(III)(CF3)3 leads to the formation of the trifluoromethylation product and a Cu(I) species. Oxalates: In 2015, Macmillan and

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• enables a rapid access to heterocycles containing a trifluoromethyl group. Keywords: cascade reaction; indole derivatives; photocatalysis; radical chain process; trifluoromethylation; Introduction Dihydropyrido[1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical

• trifluoromethyl radical source under light irradiation. Umemoto’s reagent, which is capable of releasing a trifluoromethyl radical via a photoinduced single-electron-transfer (SET) process, is usually employed to enable the trifluoromethylation of unsaturated substrates [25][26][27]. Herein, we report a protocol

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• provided a more sustainable and economically viable approach but also demonstrated excellent performance in various transformations. It had been successfully applied to a series of radical reactions, including trifluoromethylation, deaminative alkylation, and asymmetric versions of Minisci reactions

• urgent need to develop diverse monofluoromethylation methods. In this context, Chen and his colleagues recently developed a concise photocatalytic procedure for achieving monofluoromethylation, as well as di- and trifluoromethylation of various alkenes (Scheme 25) [50]. The synthetic method also

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• . Keywords: acylhydrazones; difluoromethylation; dihydropyridazine; fluorinated building blocks; hydrazones; imidazolidines; pyrazoles; pyrazolidines; pyrazolines; trifluoromethylation; Introduction The introduction of fluorine into pharmaceuticals, agrochemicals, and materials can significantly enhance

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

• compounds by transition-metal-catalyzed C–H bond activation. This review focused on the construction of C(sp2)–XRF bonds and C(sp3)–XRF bonds with an emphasis on the trifluoromethylation reaction and transformations using emergent fluorinated residues (SCF3, SeCF3, SCF2H, SCF2CO2Et or OCH2CF3 groups). Well

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• of aromatics, for which trifluoromethylation was also possible in good to high yields for electron-rich aromatic rings [10]. In this protocol, inspired by Norrish type I reactions and the elimination of β-substituents after ketone photoexcitation [11][12][13], a series of reagents containing an α

• of these reagents as late-stage functionalization agents [26][27]. For a trend in reactivity, a more comprehensive scope of arenes and heteroarenes has been explored with the innate trifluoromethylation methodology previously reported by our group [10]. Conclusion In summary, we have successfully

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• alkyl radical. Perchlorinated species 139a, like the substrates investigated by Li and Shen, most likely undergo thermal homolytic bond cleavage and do not rely on a radical initiator. In 2016, Shi and co-workers investigated the trifluoromethylation cascade of acrylamide-tethered

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

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• functionalizations of pyrrole derivatives, such as iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, and alkylation. The proposed mechanism generally involves two kinds of intramolecular cyclizations: one is 6-endo-dig cyclization to promote the formation of pyridine ring

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• conditions, more attention has been paid to this efficient strategy for C–C-bond formation. In 2015, Yu and colleagues [27] proposed a method for direct C–H trifluoromethylation of aromatic hydrocarbons through an EDA complex. Trifluoromethylated product 61 was synthesized by employing tryptamine derivative

• corresponding hydrotrifluoromethylation products with moderate to good yield. In 2017, Yu and colleagues [30] proposed an EDA-complex-induced alkyne trifluoromethylation reaction. The EDA complex formed by a catalytic quantity of Togni reagent 69 and NMM initiated the chain propagation, causing the final alkyne

• trifluoromethylation (Scheme 25). A variety of olefins, such as ene carbamates, styrene, aliphatic olefins, vinyl ethers, and acrylates are compatible in this approach, affording corresponding β-(trifluoromethyl)alkynes with good to excellent yield. The bifunctionalization was achieved by an EDA-complex-initiated

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

• 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

• under irradiation of visible light [38]. In 2017, the photoredox-catalyzed intermolecular trifluoromethylthio–trifluoromethylation and thiosulfonylation reaction of unactivated alkenes have been respectively developed by Liu [34] and Xu [42]. Recently, Qing [43] and co-workers reported an efficient anti

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores

• under the reaction conditions was also explored. Keywords: fluoroform; greenhouse gas; HFC-23; trifluoromethyl ketones; trifluoromethylation; Introduction In recent decades, organofluorine molecules have received widespread attention in the field of medicinal chemistry [1][2][3][4]. The introduction

• cost of target compounds [11][12][13][14][15]. Thus, the development of low-cost and straightforward chemical synthetic technologies, including fluorination and trifluoromethylation, are matters of considerable importance to pharmaceutical and agrochemical industries. Fluoroform (HCF3, HFC-23) is an

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• ]. Methodologies for the synthesis of trifluoromethyl compounds can be modestly divided into two general categories: the direct introduction of a CF3 group into the target position by trifluoromethylation [10][11], and the construction of a CF3 unit by transforming other functional groups [12][13]. Our group has

• developed various efficient methodologies for the electrophilic [14][15], nucleophilic [16], and radical [17] trifluoromethylation reactions for more than a decade. In recent years, we also reported the direct introduction of an acyl fluoride unit into aromatic compounds by the Pd-catalyzed cross-coupling

• they only provided two examples. In 2018, Schoenebeck and co-workers reported the decarbonylative trifluoromethylation of acyl fluorides by trifluoromethyl triethylsilane (Et3SiCF3) under Pd catalysis at high temperature (Scheme 1b) [26], although the reaction was categorized as trifluoromethylation

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• Tatsuhiro Uchikura Nanami Kamiyama Taisuke Ishikawa Takahiko Akiyama Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo, 171-8588, Japan 10.3762/bjoc.16.198 Abstract The trifluoromethylation of iodoarenes was accomplished by use of a 2

• ; catalysis; copper; fluorine chemistry; trifluoromethylation; Introduction The introduction of a trifluoromethyl group is one of the most attractive reactions in drug discovery [1][2]. In the past decade, trifluoromethylation reactions of aryl halides in the presence of transition-metal complexes were

• reported [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. CuCF3 is a useful species for the trifluoromethylation of aryl halides and there are a number of precursors of CuCF3 for trifluoromethylation reactions. In contrast, the catalytic generation of CuCF3 was less investigated [15

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• reactions. Keywords: C–H activation; energy transfer; fluorination; photocatalysis; photosensitization; visible light; Review 1 Introduction 1.1 Importance of direct C–H fluorination/trifluoromethylation and photosensitization in organic synthesis 1.1.1 Importance of fluorine atoms in organic molecules

• advantages of photosensitization, it is clear that this field has attracted less attention than PRC methods. Moreover, PS TTET is a powerful method for the fluorination and trifluoromethylation of C–H bonds. We believe this may stem from the lack of dedicated reviews grouping together the theory [103][104

• trifluoromethylation. Section 2 equips readers with the basic theory of PS TTET and provides detailed property information tables on commonly utilized PSCats in organic synthesis and especially in C–H fluorinations, grouped by their properties relevant to PS TTET. Due to the importance of moving away from transition

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• ], trifluoroacetaldehyde hemiaminals [16][17][18], N,O-acetals [19] and N,N-acetals [20], 2-(trifluoromethyl)-1,3-oxazolidines [21], and N-(tert-butylsulfinyl)trifluoroacetaldimine [11][22]. Other synthetic approaches to α-CF3-substituted amines include nucleophilic trifluoromethylation strategies [17], such as the

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• obtained using the less reactive triphenylphosphine dicobaltpentacarbonyl complex 63 as the catalyst (Scheme 35). In a later study [72], Riera and Fustero generalized the use of trifluoromethylalkynes as substrates for the PKR. The copper-catalyzed trifluoromethylation of terminal alkynes described by Qing