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

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• (Scheme 1b). As far as we know, aside from the methodologies mentioned above, there are no other reports on the direct alkylation or fluoroalkylation of these ylide compounds. In line with our ongoing interest in the chemistry of sulfoxonium ylides, we aimed to develop a new alkylation methodology using

• mechanism (path 2, right). Strategies for the synthesis of α-alkyl sulfoxonium ylides. Exploring substrate scope in the direct α-fluoroalkylation of sulfoxonium ylides. Synthetic applications of fluoroalkylated sulfoxonium ylides. Optimization of reaction conditions. Supporting Information Supporting

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

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• of a steel autoclave at 250 °C [9]. Other halogenated compounds that are not classified as freons have also been used for this type of fluoroalkylation [10][11][12][13]. We recently reported that the reaction of halothane with various phenoxides proceeded smoothly to provide various aryl

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

• alkyne product 71 initiated by an EDA complex. Mechanism of the synthesis of 2-phenylthiophene derivative 74. Synthesis of allylated product 80 initiated by an EDA complex. Synthesis of trifluoromethyl-substituted alkynyl product 84 initiated by an EDA complex. Synthesis of dearomatized fluoroalkylation

• product 86 initiated by an EDA complex. Mechanism of the synthesis of dearomatized fluoroalkylation product 86. Synthesis of C(sp3)–H allylation product 91 initiated by an EDA complex. Synthesis of perfluoroalkylation product 93 initiated by an EDA complex. Synthesis of spirocyclic indolene derivative 95

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• (CF2CF2) has advanced considerably over the last decade [20], and the use of preformed tetrafluorinated building blocks [21] provides the most efficient way of making these molecules. Recently, we disclosed a photoredox method for the reductive radical fluoroalkylation of nitrones [22][23][24]. We have

• iodine by treatment with zinc, followed by the reaction with iodine monochloride. The iodide 2b reacted quite rapidly with the nitrone but the expected fluoroalkylation product was not observed. Instead, the tetrafluorinated piperidine 3a was obtained in a moderate yield (Table 1, entry 2). Apparently

• , after the fluoroalkylation event, the reduction of the N–O bond had occurred. The corresponding addition of an additional amount of the reductant and performing the reaction in DMF led to product 3a in 84% isolated yield (Table 1, entry 4). Under the optimized conditions, a series of nitrones were

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• Vyacheslav I. Supranovich Vitalij V. Levin Alexander D. Dilman N. D. Zelinsky Institute of Organic Chemistry, Leninsky prosp. 47, 119991 Moscow, Russian Federation 10.3762/bjoc.16.126 Abstract A method for the light-mediated fluoroalkylation of silyl enol ethers with (bromodifluoromethyl

• basic conditions required to activate inert C–Si bonds with the generation of carbanionic species. On the other hand, radical reactions offer different synthetic opportunities originating from the neutral character of the intermediates [6][7] and, accordingly, radical fluoroalkylation processes have

• source of hydrogen [21]. We thought that silane 1 could couple with silyl enol ethers in the presence of a photocatalyst affording fluoroalkylation products. Indeed, silyl enol ethers were found to be good acceptors of fluorinated radicals, and the resultant silyloxy-substituted radicals underwent single

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• vinyl bromides and iodides were efficiently achieved in high yields under mild reaction conditions. Noteworthy, the transformation turned out to be functional group tolerant and highly chemo- and stereroselective (Scheme 20). The group of Hu studied the fluoroalkylation of aryl halides. Indeed, a copper

• iodoalkenes. Only examples of isolated compounds were depicted. Fluoroalkylation of aryl halides via a RCF2CF2Cu species. Synthesis of perfluoroorganolithium copper species or perfluroalkylcopper derivatives from iodoperfluoroalkanes. Formation of the PhenCuCF2CF3 reagent by means of TFE and

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

• selectivity, sustainability, and environmentally friendly bond constructions. C–H fluoroalkylation of arenes Fluoroalkylations in earlier reported methods required prefunctionalization of arenes, directing groups, etc. [175][176][177][178][179]. In this context, researchers were trying to find alternatives to

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

• , agricultural, and materials industries. The incorporation of fluorine-containing groups into organic molecules can improve their chemical and physical properties, which attracts continuous interest in organic synthesis. Among various reported methods, transition-metal-catalyzed fluorination/fluoroalkylation

• . Keywords: catalysis; C-RF bond; fluorination; fluoroalkylation; transition metals; Introduction Compared with other halogens (Cl, Br, I), fluorine (F) has completely different physical and chemical properties, such as a unique electronic structure, strongest electronegativity, and small atomic radius

• -catalyzed fluorination/fluoroalkylation reactions represent an important and hot topic in fluorine chemistry. In addition, among the various metals developed, palladium is the most commonly employed transition metal, followed by copper owing to its high efficiency and cheapness. Meanwhile, other transition

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• attention in recent years [5][6][7][8]. Thus, besides the bioisosteric relationship with ethereal oxygen [9][10][11], the CF2-unit can influence the reactivity of adjacent functional groups [12][13] and can affect conformational properties of chain and cyclic molecules [14][15]. Radical fluoroalkylation of

• hydrogen and as a trigger for the generation of free radicals mediated by visible light. Difluoroalkylation of alkenes. Isolated yields are shown. a2 equiv of the alkene were used. Fluoroalkylation of alkenes. Proposed mechanism. Optimization studies. Supporting Information Supporting Information File 220

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

• considerable importance in chemistry [26][27][28][29][30][31][32]. Enantioselective fluoroalkylation/lactonization reactions are worth investigating since a new stereogenic carbon center next to the fluoroalkyl groups is generated in products 1. To the best of our knowledge, only one successful example of an

• fluoroalkylation should be solved in the future. Further examples for the promising utilization of fluorinated phthalides as building blocks can be found in [37]. Phthalide and fluorinated phthalides (1). Plausible reaction mechanism for the formation of phthalide 1a. Synthesis of fluorinated phthalides 1

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• modern drug discovery and development area [9][10]. As a result of intensive research efforts over the last decades, efficient fluorination and fluoroalkylation methods have emerged to prepare previously challenging molecules decorated with fluorine atoms or fluorinated groups which make them practically

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• past decade, investigations mainly focused on direct fluorination or fluoroalkylation of aromatics [1][2][3][4][5]. Fluoroalkylated alkenes are a kind of important fluorinated structural motifs and have wide applications in medicinal chemistry and advanced functional materials [6][7][8][9]. However

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

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

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

• -okayama, Meguro-ku, Tokyo 152-8552, Japan 10.3762/bjoc.11.286 Abstract This short review highlights the copper-mediated fluoroalkylation using perfluoroalkylated carboxylic acid derivatives. Carbon–carbon bond cleavage of perfluoroalkylated carboxylic acid derivatives takes place in fluoroalkylation

• reactions at high temperature (150–200 °C) or under basic conditions to generate fluoroalkyl anion sources for the formation of fluoroalkylcopper species. The fluoroalkylation reactions, which proceed through decarboxylation or tetrahedral intermediates, are useful protocols for the synthesis of

• , the research activity on selective fluorination and trifluoromethylation has reached a mature state. The progress in fluoroalkylation of organic compounds could be accelerated by the use of fluoroalkylating reagents, which are inexpensive and easy to handle. Perfluoroalkyl carboxylic acid derivatives

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• by nucleophilic substitution reactions using [18F]-fluoride ion (Scheme 7) [55][56][57][58][59][60][61][62][63][64][65][66][67]. For not only fluorination/fluoroalkylation, but also for defluorination, flow microreactor synthesis is quite effective. Defluorination involving a nucleophilic addition

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

• monofluoromethylation was described by J. Hu. Aryl iodides were submitted to a Cu-catalyzed (CuTC = copper thiophene-2-carboxylate) debenzoylative fluoroalkylation with 2-PySO2CHFCOR followed by desulfonylation (Scheme 2) [49]. It has been shown that the (2-pyridyl)sulfonyl moiety is important for the Cu-catalysis. 2

• decarboxylative fluoroalkylation (Table 1) [61]. A wide range of α,β-unsaturated carboxylic acids afforded the corresponding difluoromethylated alkenes in high yields and with excellent E/Z selectivity. The putative mechanism for this copper-catalyzed decarboxylative fluoro-alkylation involves the iodine–oxygen

Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me₃SiCF₂SO₂Ph and PhSO₂CF₂H reagents catalyzed by chiral quaternary ammonium salts

• Chuanfa Ni,
• Fang Wang and
• Jinbo Hu

Beilstein J. Org. Chem. 2008, 4, No. 21, doi:10.3762/bjoc.4.21

• agrochemicals and 20% of pharmaceuticals on the market contain fluorine [1][2]; as a result, fluorine is highlighted as the second most utilized hetero-element (after nitrogen) in life science-oriented research [3]. Nucleophilic fluoroalkylation, typically involving the transfer of a fluorinated carbanion (Rf

• played an important role in tuning the fluoroalkylation reactivity towards aldehydes and ketones, i.e. aldehydes showed higher reactivity than ketones [12]. In connection with our studies on selective fluoroalkylation reactions, herein we disclose the first example of catalytic enantioselective