The Preparation and Utility of Pentafluorosulfanyl Substituted Aliphatic Compounds

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Rarely in chemistry does the opportunity to explore the chemistry of a new functional group appear. The pentafluorosulfanyl (SF5) group, one of the few new functional groups of the last 100 years, has the potential to dramatically impact both life sciences and materials chemistry. The SF5 group presents a square pyramid of sulfur-bound fluorines to receptors yet occupies a volume somewhat less than the tert-butyl group. The large dipole moment in the carbon-SF5 bond results in long range electrostatic interactions of the substrate molecule. As the core building blocks of an enormous number of biologically relevant molecules, the synthesis of aliphatic SF5 containing carbonyl compounds quickly and economically is invaluable. The stereochemistry of reactions of cyclic and acyclic SF5-containing aldehydes, ketones and oxocarbenium ions with nucleophiles will be elucidated. Both the steric effects and electrostatic interactions of pentafluorosulfanylation can be employed in the synthesis of carbohydrates, amino acids and azetidinones from SF5-containing building blocks. The broader impact. Of vital economic and social importance, the utility of many organofluorine compounds is plagued by both metabolic and environmental limitations. The ready availability of these new SF5-containing molecules can be the first step in replacing trifluoromethylated agrichemicals that persist in the environment with adverse effects on both humans and animals. As replacements in pharmaceutical agents, facile SF5 group metabolism to substances that are not immunologically or enzymatically toxic may expand the utility of anti-malarial or anxiolytic drugs. The proposed program trains the next generation of students in basic synthetic fluorochemical and physical organic chemistry. Students will utilize multi-dimensional NMR methods and ab initio computational techniques. Students engaged in this cross-disciplinary project will be prepared to join other scientists and engineers with multidisciplinary backgrounds and experience in research and problem-solving. Within the last three years, PI has mentored nine students from historically under represented groups. Of these students, to date, five have continued their studies in graduate school. The development of a new functional group and its applications in synthesis can have an impact on nearly all areas of organic chemistry and offers a uniquely American technology to our industries. The product of the proposed research clearly has direct applicability to the development of new building blocks for medicinal chemistry and materials science as well as the potential to illustrate new strategies for the control of asymmetry in synthesis, a basic requirement of 21st century preparative methods.