The role of fluorine in drug design and development is expanding rapidly as we learn more about the unique properties associated with this unusual element and how to deploy it with greater sophistication. The judicious introduction of fluorine into a molecule can productively influence conformation, pKa, intrinsic potency, membrane permeability, metabolic pathways, and pharmacokinetic properties. In addition, 18F has been established as a useful positron emitting isotope for use with in vivo imaging technology that potentially has extensive application in drug discovery and development, often limited only by convenient synthetic accessibility to labeled compounds. The wide ranging applications of fluorine in drug design are providing a strong stimulus for the development of new synthetic methodologies that allow more facile access to a wide range of fluorinated compounds. In this review, we provide an update on the effects of the strategic incorporation of fluorine in drug molecules and applications in po...

Applications of Fluorine in Medicinal Chemistry

Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow Until recently, however, the question, “Should we do this in flow?” has merely been an afterthought This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts

The Hitchhiker's Guide to Flow Chemistry

Good Partnership between Sulfur and Fluorine: Sulfur-Based Fluorination and Fluoroalkylation Reagents for Organic Synthesis

Monofluorination of Organic Compounds: 10 Years of Innovation.

A Friedel–Crafts benzylation of arenes with benzyl fluorides has been developed. The reaction produces 1,1-diaryl alkanes in good yield under mild conditions without the need for a transition metal or a strong Lewis acid. A mechanism involving activation of the CF bond through hydrogen bonding is proposed. This mode of activation enables the selective reaction of benzylic CF bonds in the presence of other benzylic leaving groups.

Friedel–Crafts Reaction of Benzyl Fluorides: Selective Activation of C ? F Bonds as Enabled by Hydrogen Bonding

For more than three decades, the ability of a fluorine atom involved in a C–F bond to act as a hydrogen-bond acceptor has been a controversial issue. Throughout the years, more and more evidence has been published to support this hypothesis and it is now difficult to doubt the existence of the hydrogen bond with organic fluorine. However, since this interaction has low binding energies, it is sometimes difficult to clearly demonstrate its presence or effect in a system. In the present review, only the most recent examples from the literature are presented and the different techniques used to prove the presence of these C–F···H–X hydrogen bonds are compared and discussed according to the accepted criteria for hydrogen bonding detailed by a recent IUPAC committee. Even with its weak interaction energy, hydrogen bonds to organic fluorine have the potential to affect properties of practical systems in different spheres of chemistry. All the recent examples of such effects are highlighted. 1 	Introduction 2 	Properties 3 	C(sp2)–F 3.1 	O–H as Donor 3.2 	N–H as Donor 3.3 	C(sp2)–H as Donor 3.4 	C(sp3)–H as Donor 4 	C(sp3)–F 4.1 	O–H as Donor 4.2 	N–H as Donor 4.3 	C(sp2)–H as Donor 4.4 	C(sp3)–H as Donor 5 	Conclusion

Justine Desroches

Papers

Monofluorination of Organic Compounds: 10 Years of Innovation.

Friedel–Crafts Reaction of Benzyl Fluorides: Selective Activation of C ? F Bonds as Enabled by Hydrogen Bonding

Organic Fluorine as a Hydrogen-Bond Acceptor: Recent Examples and Applications

Halogenation of Primary Alcohols Using a Tetraethylammonium Halide/[Et2NSF2]BF4 Combination

Faster initiation in the Friedel-Crafts reaction of benzyl fluorides using trifluoroacetic acid as activator