The preparation and biological activity of pentafluorosulfanyl-containing compounds

FLUO 7

John T. Welch, jwelch@uamail.albany.edu, Department of Chemistry, University at Albany, 1400 Washington Avenue, Albany, NY 12222, Dong Sung Lim, dl0041@albany.edu, Department of Chemistry, University at Albany - SUNY, 1400 Washington Avenue, Albany, NY 12222, Gauri, S Lal, lalgs@apci.com, Corporate Science & Technology Center, Air Products and Chemicals Inc, 7201 Hamilton Boulevard, Allentown, PA 18195, and Kristin E. Minnich, minnicke@apci.com, Corporate Science & Technology Center, Air Products and Chemicals, Inc, 7201 Hamilton Boulevard, Allentown, PA 18195-1501.
The utility of the pentafluorosulfanyl group in medicinal or pharmaceutical chemistry is only beginning to be explored. The introduction of this functional group presents the opportunity to explore the influence on biological activity of the unusual octahedral substitutent with an electron rich fluorine periphery. Conceptually an analog of the trifluoromethyl group, the preparation of analogs of biologically active trifluoromethylated compounds requires the ready availability of pentafluorosulfanyl containing reagents and building blocks, materials which only recently have become readily available. We have prepared analogs of the herbicide-treflan (1), the antidepressant-fluoxetine (2), and the anorectic- fenfluramine (3). In addition to these syntheses we have explored the reactivity of pentafluorosulfanyl arenes in electrophilic substitution reactions and in the formation of organometallic reactions while also considering the overall stability of this unusual substituent to routine synthetic transformations.