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      Recent advances in transition metal-catalyzed Csp 2-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

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          Summary

          In the last few years, transition metal-mediated reactions have joined the toolbox of chemists working in the field of fluorination for Life-Science oriented research. The successful execution of transition metal-catalyzed carbon–fluorine bond formation has become a landmark achievement in fluorine chemistry. This rapidly growing research field has been the subject of some excellent reviews. Our approach focuses exclusively on transition metal-catalyzed reactions that allow the introduction of –CFH 2, –CF 2H, –C n F 2 n +1 and –SCF 3 groups onto sp² carbon atoms. Transformations are discussed according to the reaction-type and the metal employed. The review will not extend to conventional non-transition metal methods to these fluorinated groups.

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          Fluorine in medicinal chemistry.

          It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.
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            Fluorine in pharmaceuticals: looking beyond intuition.

            Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
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              A survey of Hammett substituent constants and resonance and field parameters

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                Author and article information

                Contributors
                Role: Guest Editor
                Journal
                Beilstein J Org Chem
                Beilstein J Org Chem
                Beilstein Journal of Organic Chemistry
                Beilstein-Institut (Trakehner Str. 7-9, 60487 Frankfurt am Main, Germany )
                1860-5397
                2013
                15 November 2013
                : 9
                : 2476-2536
                Affiliations
                [1 ]CNRS-Université de Strasbourg, UMR 7509, SynCat, ECPM, 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France
                [2 ]Bayer CropScience AG, Alfred-Nobel-Strasse 50, 40789 Monheim, Germany
                [3 ]Bayer SAS, 14 impasse Pierre Baizet, 69263 Lyon, Cedex 09, France
                Author notes
                [§]

                http://www.syncat.org

                Article
                10.3762/bjoc.9.287
                3869273
                24367416
                75447ae4-3cf8-494c-85c1-d9d0b520efa7
                Copyright © 2013, Landelle et al; licensee Beilstein-Institut.

                This is an Open Access article under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: ( http://www.beilstein-journals.org/bjoc)

                History
                : 30 July 2013
                : 10 October 2013
                Categories
                Review
                Chemistry
                Organic Chemistry

                Organic & Biomolecular chemistry
                catalysis,cross-coupling,difluoromethylation,fluorine,monofluoromethylation,organo-fluorine,transition metal,trifluoromethylation,trifluoromethylthiolation

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