Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• diastereotopic fluorines. Moreover, the possibility of experiencing both the generalized anomeric and gauche effects makes the Ishikawa´s reagent an ideal choice to study the governing stereoelectronic interactions of the conformational equilibrium of organofluorine compounds. The conformational equilibrium of

• : anomeric effect; gauche effect; NMR spectroscopy; organofluorine compounds; Introduction The active species of Ishikawa´s reagent [N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine, 1] [1] (Figure 1) has diastereotopic substituents (fluorines), which can be useful to provide conformational insights by using

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• ][6]. Notably, organofluorine compounds bearing a tetrafluoroethylene (–CF2CF2–) unit have attracted significant interest as a promising framework for various functional molecules. In the medicinal field, for example, Linclau and co-workers reported the first enantioselective synthesis and the

• here should be a suitable and valuable tetrafluoroethylenating agent for preparing various CF2CF2-containing molecules, thereby providing a powerful and practical synthetic tool in organofluorine chemistry. Functional molecules with CF2CF2-fragment. Recovery yield of 2-Zn in DMF (ca. 0.70 M) after

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

• Vyacheslav I. Supranovich Vitalij V. Levin Marina I. Struchkova Jinbo Hu Alexander D. Dilman N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian Federation Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai

• with blue light is described. The reaction involves radical addition of 1,1-difluorinated radicals at the double bond followed by hydrogen atom transfer from sodium cyanoborohydride. Keywords: difluoroalkylation; organofluorine compounds; radical addition; visible light; Introduction Applications of

• organofluorine compounds in medicinal chemistry and related fields [1][2] have stimulated intensive developments of methods for their synthesis [3][4]. Though the major emphasis has long been placed on trifluoromethylated molecules, compounds bearing the difluoromethylene fragment have attracted increasing

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

• -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

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• ; electrosynthesis; fluorobenzothiophenone; selective fluorination; Introduction Due to the interesting properties of fluorine atoms and carbon–fluorine bonds, organofluorine compounds are widely used in various fields like pharmaceutical chemistry, agrochemistry, and materials sciences [1][2]. Therefore, the

• selective fluorination of organic compounds is highly useful for the development of novel organofluorine compounds. Although a number of fluorination reagents have been developed so far, they have still some problems, i.e., they are costly, difficult to handle, and explosive [3][4]. On the other hand

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

• structures of various pharmaceuticals, agrochemicals and coatings contain fluorine or fluorinated functional groups [4][5][6][7][8][9]. Therefore, the development of efficient synthetic methodologies for organofluorine compounds has gained much attention [10][11][12][13][14][15]. Our research group has been

• ]. Utilizing these reagents, we have successfully synthesized a wide variety of bioactive organofluorine compounds [24][25][26][27][28][29][30] including fluorinated thalidomide (antitumor) [24], fluorinated donepezil (cholinesterase inhibitor) [25], and fluorinated camptothecin (anticancer) [26]. During our

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• Foundation of China (NSFC 21472213, 21272069), National Key Program (2016YFA0200302, Study on application and preparation of aroma nanocomposites), the Fundamental Research Funds for the Central Universities and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese

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

• synthesis of useful bioactive compounds. There is a growing interest in the usefulness of phthalides and their derivatives. Organofluorine compounds often show attractive physical, chemical, and biological properties and are widely used in many fields, such as pharmaceuticals, agrochemicals, and materials

• [3][4][5][6][7][8][9][10]. Selective incorporation of fluorine or a fluoroalkyl group into a molecule is a topic of significant interest in organic chemistry. Fluorinated phthalides are considered to be one of the most fascinating organofluorine compounds. However, to our best knowledge, there have

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• fascinating molecular properties of organofluorine compounds exerted by the fluorine atom, our research group has devoted sustained effort to the development of novel biologically active fluorinated substances and high-functional fluorinated materials thus far [7][8][9]. Our recent interest inspired by the

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

• ; Introduction In organofluorine chemistry, the CF3 group occupies a place of choice as privileged structural motif in the development of multifaceted catalysts and ligands for organic synthesis as well as in the design of pharmaceuticals, agrochemicals and specialty materials [1][2][3][4]. The trifluoromethyl

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

• Organofluorine compounds now play an essential role in the development of new materials for solar cells [1][2][3], radiotracers for PET imaging [4], agrochemicals [5][6], sensitive chemical probes for 19F nuclear magnetic resonance investigation of biological experiments [7][8], and are most widely used in the

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

• Tao Fan Wei-Dong Meng Xingang Zhang College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Road, Shanghai 201620, China, Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• ; polarity; Introduction Fluorine is a rare element in natural biochemical settings [1]. Notwithstanding several prominent fluoro-organic metabolites in nature [2][3], fluorine is virtually absent from natural biopolymers such as proteins and nucleic acids. Therefore, organofluorine groups lack a natural

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• configurations that can affect the conformation. Organofluorine chemistry offers a particular attraction here, since fluorinated molecules (e.g., 3–5) tend to adopt predictable conformations due to hyperconjugative and/or dipole–dipole interactions associated with the C–F bond [11][12][13][14][15]. Such a

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the

• -fluorocyclohexanone; hyperconjugation; Introduction Organofluorine compounds are of special interest in materials, pharmaceutical and agricultural sciences, as the C–F bond is the most polar bond in organic chemistry, which can be useful in the design of performance organic molecules [1]. A fluorine substituent in

• organofluorine compounds affects conformational properties, since it can induce stereoelectronic effects, such as σC–H to σ*C–F hyperconjugative interactions in case of an antiparallel oriented C–H bond. This is the origin of the so-called 'gauche effect', because electronegative C–X bonds do not participate in

Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

• Mathew J. Jones,
• Ricardo Callejo,
• Alexandra M. Z. Slawin,
• Michael Bühl and
• David O'Hagan

Beilstein J. Org. Chem. 2016, 12, 2823–2827, doi:10.3762/bjoc.12.281

• each other in a cyclohexane ring is introduced as a new design strategy which could be applicable to the preparation of polar hydrophobic cyclohexane motifs. Keywords: aliphatic rings; C–F bond; cyclohexane conformation; difluoromethylene group; organofluorine chemistry; Introduction Selective

Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand–metal interactions

• Stefan Mark,
• Hubert Wadepohl and
• Markus Enders

Beilstein J. Org. Chem. 2016, 12, 1372–1379, doi:10.3762/bjoc.12.131

• do not interact with the coordinatively saturated chromium centers. The coordination ability of the chosen donors D range from very weak (organofluorine) to medium (olefinic or aryl, respectively) and strong (nitrile). Activation with methylaluminoxane (MAO) leads to the formation of monomethyl

• hemilabile donor in terms of catalyst activity and molecular weight of the polymer. Results and Discussion It is well known that early transition metal single-site polymerization catalysts can interact with organofluorine groups [15][17][20][22]. In FI-type catalysts the interaction of fluorine substituents

• organofluorine substituent is connected by a side arm with suitable length. In addition to that we choose side arms with olefinic groups, a benzyl unit and a stronger nitrile donor group, respectively. The synthesis of the new ligand derivatives and the corresponding Cr complexes follows known procedures (Scheme

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. Keywords: cyclohexane carbonylation; fluorine containing building blocks: organofluorine chemistry; Introduction Selectively fluorinated building blocks

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

• contributed to the advancement of human life and the global demand for organofluorine compounds will continue to increase. Therefore, the introduction of fluorine-containing functional groups into organic molecules is recognized as a general strategy for the design of drugs and functional materials. In fact

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• dimethylformamide under ligand-free conditions. Keywords: 1-bromoalkynes; cross-coupling; organofluorine compounds; organozinc reagents; Introduction gem-Difluorinated organic compounds have attracted increasing attention nowadays due to their applicability in medicinal chemistry [1][2] and other fields. Indeed

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• thioester enols and enolates, important intermediates in enzymatic C–C bond forming reactions. The method opens access to appropriate analogues for investigations in this direction. Keywords: alkynyl sulfides; α-fluorovinyl thioethers; hydrofluorination; Lewis acids; organofluorine; Introduction

• Organofluorine compounds have found wide use in tuning the properties of performance compounds in medicinal and materials chemistry [1][2]. Also the electronegativity of fluorine has been used to design and tune steric and electronic mimetics of functional groups for applications in biomolecular chemistry. For

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• eventually open up for just such a possibility. Trifluoroacetic acid (CF3CO2H) has been known since 1922 [21], but its widespread application was only made possible sometime later, much due to the development of electrochemical fluorination processes (Simons process) for production of organofluorine

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• fluorine atom(s) into organic molecules very often improves or enhances their desired characteristic physical and biological properties hence organofluorine compounds are highly useful for medicinal, agrochemical, and materials science [1][2][3][4][5][6]. In order to prepare new fluorine compounds

Direct C–H trifluoromethylation of di- and trisubstituted alkenes by photoredox catalysis

• Ren Tomita,
• Yusuke Yasu,
• Takashi Koike and
• Munetaka Akita

Beilstein J. Org. Chem. 2014, 10, 1099–1106, doi:10.3762/bjoc.10.108

• multisubstituted CF3-alkenes from simple aryl alkenes is the first report. In addition, we can extend the present photocatalytic system to double trifluoromethylation. Further development of this protocol in the synthesis of bioactive organofluorine molecules and fluorescent molecules is a continuing effort in our

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• ; indoles; tandem reactions; Introduction Introducing fluorine atoms into organic molecules still faces challenges in organic synthesis [1]. Organofluorine compounds found growing use in various areas including pharmaceuticals, agrochemicals, and materials [2]. A significant proportion of pharmaceuticals