Chiral organofluorine compounds

Chiral organofluorine compounds containing a fluorine atom bonded directly to a stereogenic center have been used in a variety of research investigations, including mechanistic studies of enzymes and intermediates in the asymmetric synthesis of bioactive compounds. The development of effechve methodologies for the... 

Myers AG, Barbay JK, Zhong B (2001) Asymmetric synthesis of chiral organofluorine compounds use of nonracenuc fluoroiodoacetic acid as a practiced electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteies within a novel series of HIV protease inhibitors. J Am Chem Soc 123 7207-7219... 

For reviews see. (a) Welch, J. T. (1987) Tetrahedron report number 221 Advances in the preparation of biologically active organofluorine compounds. Tetrahedron, 43, 3123-3197. (b) Resnati, G. (1993) Synthesis of chiral and bioactive fluoroorganic compounds, Tetrahedron, 49, 9385-9445. (c) Soloshonok, V. A. (ed.) (1999) Enantiocontrolled Synthesis of Fluoroorganic Compounds Stereochemical Challenges and Biomedicinal Targets, John Wiley Sons, Ltd, Chichester, UK. (d) Rosen, T. C., Yoshida, S., Kirk, K. L. and Haufe, G. (2004) Fluorinated phenylcyclopropylamines as inhibitors of monoamine oxidases. ChemBioChem., 5, 1033-1043. 

The quest for methods of synthesizing chiral fluoroorganic compounds is one of the most fascinating topics in modern organofluorine chemistry because the replacement of hydrogen with a fluorine atom often results in a significant improvement in the physicochemical properties and biological activities of the molecules. 

During the past decade, there has been an increased emphasis on new approaches to chiral compoimds and asymmetric syntheses. This focus has been particularly pronounced in medicinal chemistry, where a specific enantiomer or diastereomer often exhibits enhanced therapeutic potency compared with the racemate. Organofluorine compounds have played a significant role in these advances. An earlier report emphasized a range of methods for the synthesis of chiral bioactive fluoroorganic compounds (1). Since the intent of this paper is to provide an overview which captures the scope and flavor of these recent developments, it seems quite appropriate to briefly cite the fascinating range of research studies of the other contributors to this book. 

Asymmetric synthesis of organofluorine compounds is an important issue in pharmaceutical chemistry 1,2) and optoelectronic material science 3,4). In particular, asymmetric catalysis of carbon-carbon bond-forming reactions is the most attractive method, because the carbon skeleton of chiral organofluorine molecules can be constructed at the time of asymmetric induction 5-10). The Friedel-Crafts (F-C) reaction is one of the most fundamental carbon-carbon bondforming reactions in organic synthesis 11-14). However, its application to catalytic asymmetric synthesis has been quite limited (diastereoselective 25-22, enantioselective 23-25, stereospecific 2d,2. Herein, we report the catalytic... 

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