Novel Polyfluoroalkylated Building Blocks

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Through this award, the Chemical Synthesis Program of the Division of Chemistry supports work by Professor Gary Molander of the University of Pennsylvania in developing synthetic approaches to a class of fluorinated organic compounds. The presence of fluorine in organic molecules is known to have profound effects upon bioavailability and/or stability. Families of versatile, stable, perfluoroalkyl-substituted building blocks are being constructed that can be installed in large fragments through the development of a variety of carbon-carbon and carbon-heteroatom protocols. Success in these regimes will provide methods for the synthesis of organic molecules with extensive fluorination, expanding and creating novel chemical space by methods that increase molecular complexity in highly convergent yet modular synthetic processes. These highly flexible, prefabricated subunits thus provide a platform around which to build libraries of molecules for investigation of their properties within the context of the pharmaceutical or agrochemical industries, for example, facilitating the discovery of novel compounds with unique properties and providing these industries new tools to bring innovative molecules to the market more efficiently and at lower cost. The importance of embedding fluorine atoms within organic molecules to alter their physicochemical and biological properties has been firmly established, and thus the selective introduction of trifluoromethyl groups, as well as polyfluorinated alkyl groups, has consequently been of high interest to the synthesis community. Most of these efforts have supported the installation of fluoro- or trifluoromethyl groups onto aromatic systems. By contrast, general methods for the incorporation of functionalized, perfluorinated subunits into alkyl systems, particularly in an enantioselective manner, is much less well developed, yet increasingly more important in terms of structural diversity and expanding chemical space. The research to be carried out will allow the development of operationally simple and effective routes to borylated organofluorine materials. The first subgoal of the investigations is to develop convenient syntheses of a diverse family of stable, polyfluorinated alkylboron reagents to be used for the incorporation of perfluoroalkyl units into alkyl substructures.