(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 109 (Scheme 12A) [58]. The formed products all contained a pendant primary iodide group and the synthesis was additionally shown to be tolerant of functional groups including protected amines (in 110c), protected alcohols (in 110d) and nitriles (in 110e). Grygorenko and co-workers accessed fluorine

• -containing 2-oxa-1,4-BCH 110b via Mykhailiuk’s synthesis [59]. 2-Oxa-1,4-BCH 110f, which contained a bridgehead ester in addition to the pendant primary iodide, was found to be a versatile synthetic intermediate. Substitution of the primary iodide with acetate or azide led to alcohol 111 and amine 113

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• esters; Introduction The insertion of fluorine-containing components frequently confers desirable physical and biological properties to organic molecules, and the development of fluorine-containing drugs is an important field of research [1][2][3][4][5][6][7][8][9]. It is estimated that 30% of drugs and

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

• . Hydrazones can be regarded as electrophilic and nucleophilic imine equivalents, and thus they represent valuable and versatile building blocks in synthetic chemistry [32][33][34][35][36]. Trifluoroacetaldehyde hydrazones can be regarded as an equivalent of fluorine-containing azomethine imines in the

• blocks for the synthesis of heterocycles [46][47]. The resultant heterocycles bearing a fluorine or fluorine-containing group have been used in a broad array of pharmaceutical applications [48][49]. The use of di/trifluoromethylated hydrazonoyl halides as building blocks for the synthesis of di

• dipolarophiles in the [3 + 2]-cycladditions (Scheme 19b). Conclusion Fluorine-containing molecules have attracted widespread attention as important components of agrochemicals, pharmaceuticals, and advanced materials. Abundant and fruitful progress in the applications of fluoromethylated hydrazones and

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

• largely underexplored to date. Furthermore, the development of enantioselective transformations allowing the synthesis of enantioenriched fluorine-containing compounds by transition-metal-catalyzed C–H bond activation will have a significant impact as for instance an access to pharmaceutically relevant

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• promising leads within the OSM project [14]. Fluorine-containing compounds have exhibited wide applications in pharmaceuticals and agrochemicals – approximately 20% of marketed drugs are fluoro-pharmaceuticals, while for agrochemicals, 53% are fluoro-compounds [17][18]. In recent decades, the introduction

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

• ) has been used as a fluorine-containing building block for the construction of trifluoromethyl and difluoromethylene motifs [1][2]. Such structures have been found in several multifunctional materials and biologically important molecules (Figure 1) [3][4][5][6][7]. The halothane structure contains two

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives. Keywords: functionalization; metathesis; nitrile oxide

• are considered as to be of type II, only a handful of literature data are available on the behavior of fluorine-containing olefins or perfluorinated alkenes. The incorporation of fluoroalkyl moieties (such as difluoromethyl, trifluoromethyl and perfluoroalkyl groups) into an organic molecule can often

• ) late-stage fluorination, when the fluorine atom is incorporated in the final step of the synthetic protocol (e.g., deoxofluorinations) or ii) application of various commercial fluorine-containing scaffolds (e.g., fluorine-containing amines, fluorine-containing alkenes etc.) [49][50][51][52][53][54][55

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

• also been reported for the direct C(sp3)–H fluorination. Chen and co-workers [94] described a fluorination method employing Selectfluor as fluorine source and the commercially available V2O3 to give fluorine-containing compounds under mild conditions and with moderate to good yields (Scheme 10B,C). The

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• advantages of the presence of an alkoxyphenyl substituent in the side chain, providing an efficiency of 5.23%. Therein, the presence of a substituent in the phenylene fragment is also an important factor (Table 6). Thus, an OSC based on a fluorine-containing polymer showed an efficiency of only 0.93%. This

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• fluorine-containing organic molecules combined with the 1,4-quinone moiety can be considered as a challenging problem of current organic synthesis. Thus, the main goal of the present study was to check the course of [3 + 2]-cycloaddition reactions of electron-deficient CF3-substituted nitrile imines 7 with

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• ]. Longer reaction times and lower temperatures were used to improve the first step that resulted in very good yields. Recently, Xiao et al. used this method for the synthesis of 13 new fluorine-containing proguanil derivatives which were found to be more active than proguanil in five human cancerous cell

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

• by introducing fluorine-containing (such as -CF3, -CF2H, -C2F5, -SCF3, -OCF3) moieties has become a substantial strategy for medicinal research [2][7][8]. Among the fluorinated functionalities, the trifluoromethylthio group (SCF3) has strong electron-withdrawing properties and a higher lipophilicity

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• properties. These factors may translate into an altered structure and stability of a protein containing a fluorinated fragment. What consequences fluorination would have regarding the fitness and survival of the organism relying on fluorine-containing proteins remains an open question. In this context, the

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

• , Nagoya 466-5888, Japan Tosoh Finechem Corporation, 4988, Kaiseicho, Shunan, 746-0006, Japan Institute of Advanced Fluorine-Containing Materials, Zhejiang Normal University, 688 Yingbin Avenue, 321004 Jinhua, China 10.3762/bjoc.17.39 Abstract A straightforward method that enables the formation of

• examined [46]. Trifluoromethyl ketones (TFMKs) are valuable fluorine-containing synthetic targets of bioactive compounds [55][56] that behave as mimics of the tetrahedral transition-state intermediate of enzymatic hydrolysis of esters and amides by stabilizing their hydrates (Figure 1a) [57]. In fact, the

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• powerful tool for assembling a variety of fluorinated carbo- and heterocycles using either the diene [24][25][26][27][28][29][30] or the dienophile component [31][32][33][34][35][36][37][38][39] as fluorine-containing building blocks. The application of [4 + 2] cycloadditions for the preparation of

• fluorinated bicyclic compounds has attracted much attention [40][41][42][43][44][45][46][47]. In this regard, the development of new protocols to relevant monofluorinated bicyclic molecules involving novel versatile fluorine-containing building blocks is of key importance. Fluoroalkenes are recognized to be

• one of the most widely used fluorine-containing building blocks [48][49]. Recently, we have developed an efficient stereoselective synthesis of β-fluoro-β-nitrostyrenes 1 based on the radical nitration of 2-bromo-2-fluorostyrenes [50]. This process takes place with simultaneous elimination of bromine

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the gem-dihalomethylene fragment. Thus, they are of interest not only for the direct application as biologically active substances and functional materials but also as precursors to other fluorine-containing compounds [1][2]. Fluorine forms stable bonds to carbon and due to its high electronegativity

• difluorocyclopropane and its derivatives can be distinguished: carbene and non-carbene methods of cyclopropanation along with functional group transformations of existing cyclopropanes. The most popular route to prepare fluorocyclopropanes is to generate fluorine-containing carbenes (or carbenoids), which then react

• with multiple bonds, resulting in cyclopropanation. One of the important properties of fluorine-containing carbenes and carbenoids is their electrophilicity, which is a result of the high electronegativity of fluorine. Also, fluorine has an +M effect which tends to reduce the reactivity of the carbenes

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• thermally activated delayed fluorescence (TADF) emitters. In the present study, we investigate computationally the potential of other fluorine-containing acceptors, trifluoromethoxy (OCF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5), within two families of donor–acceptor TADF emitters. Time

• within TADF emitter design (Figure 1) [25][26][27]. In the present study, we report on the impact of incorporating other fluorine-containing electron-withdrawing groups beyond trifluoromethyl (CF3), including trifluoromethoxy (OCF3), trifluoromethylthio (SCF3), and pentafluorosulfanyl (SF5) groups, and

• , and 2CzBP of −1.70 eV, −1.63 eV, and −1.67 eV, respectively, are much deeper those of the fluorine-containing emitters in Figure 3, which is a reflection of the greater conjugation length present in compounds with an extended π-accepting framework. The corresponding ΔEg of 2CzBN (4.19 eV), 2CzTRZ

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• ; salicylate derivatives; Introduction It is well known that the incorporation of a fluorine atom or a fluorine-containing group into organic compounds sometimes affects their original biological activities [1][2][3], and thus the development of methods for the construction of such molecules with this atom or

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

• directly from readily available alcohols. Keywords: alcohols; benzothiazolium salts; deoxygenative reactions; fluorine; perfluoroalkylthiolation; thioethers; Introduction The incorporation of fluorine-containing groups into organic molecules to modulate their biological or physical properties is nowadays

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

• -5888, Japan Pharmaceutical Division, Ube Industries, Ltd., Seavans North Bldg, 1-2-1 Shibaura, Minato-ku, Tokyo 105-8449, Japan Institute of Advanced Fluorine-Containing Materials, Zhejiang Normal University, 688 Yingbin Avenue, 321004 Jinhua, China 10.3762/bjoc.16.254 Abstract A new protocol enabling

• fluorine-containing functional groups into organic molecules has become a common strategy in pharmaceutical and agrochemical industries [1][2][3][4][5]. Among various fluorine-containing functional groups, the trifluoromethyl (CF3) group has received countless attention in the design of novel drugs [6][7

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• investigational therapeutic agents, including antitumorals and antivirals […]” [8]. Interestingly, most fluorine-containing benzimidazoles contain the fluorinated substituent either on the aromatic ring or on a side chain connected to the aromatic ring; examples of benzimidazoles containing a fluoroalkyl group

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• -nucleophile; CF3-aldimine; fluorinated propargylamine; Introduction In recent years, substitution of hydrogen by fluorine atoms or fluorine-containing groups usually provides unexpected biological and physicochemical properties, which thus has become an established approach for the development of

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• Deoxo-Fluor®. The fluorine-containing products thus obtained were subjected to elimination reactions, yielding various fluorine-containing small-molecular entities. Keywords: fluorine; fluoroselenation; functionalization; halofluorination; stereocontrol; Introduction The effects of fluorine on

• discovering new reagents and conditions for the introduction of fluorine and fluorine-containing groups into a certain organic molecule [11][12][13][14][15][16][17][18], several known methods have been studied and improved over the past decade. One such long-known method is halofluorination. During this

• uncovered, too. The oxidation of (rac)-31 under basic conditions delivered the conjugated diene (rac)-34, possibly through a deselenation/E1cB elimination sequence similar to the one shown in Scheme 22. Conclusion In conclusion, novel fluorine-containing, functionalized small-molecular scaffolds have been

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• fluorine-containing agrochemicals. Accordingly, this study aims to determine the most likely conformers of some fluorine-containing agrochemicals and to correlate their molecular dipole moments with the respective n-octanol/water partition coefficients (log P), in order to investigate the dependence of the

• helps in explaining the expressive amount of fluorine-containing agrochemical candidates (around 30%) as well as pharmaceuticals (around 20%) [5][6]. In this sense, the chemistry of fluorine-containing compounds has been extensively investigated in order to better understand the effects of fluorination

• substituents originated from the rotation of fluorine-containing C–C bonds should affect the polarity and, therefore, the physicochemical and biological properties of organofluorine compounds. However, there is a lack of studies that explain how these well-known conformational effects directly alter

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• conditions. There are a few thorough studies on this reaction with pyrimidine and purine nucleoside bases and their derivatives which are most closely related to fluorine-containing substrates 1 [40][41][42]. However, considering the high sensitivity and capricious nature of CEL reaction, we wish to report