Nitrogen-containing sulfur(VI) compounds, such as sulfamides, sulfonamides, and sulfones, are found in ~27% of sulfur-containing drugs administered by the United States Food and Drug Administration. Synthesis of these compounds have been historically performed via the oxidation of thiols or the substitution of sulfur(VI) chlorides precursors. The former occurs under harsh conditions, limiting functional group compatibility; the latter is thermodynamically unstable and susceptible to hydrolysis and redox reactions. Sulfur(VI) fluorides have emerged as promising alternative precursors toward the synthesis of nitrogen-containing sulfur(VI) compounds via sulfur-fluorine exchange (SuFEx) chemistry. A recent experimental study has reported the use of stoichiometric calcium triflimide (CaNTf2)2 – one of the few reports that employ a Lewis-acid mediated process. However, given the difficulty in isolating Ca2+ intermediates along the reaction pathway, the mechanism of this process is unknown. Our work uses DFT computations to probe plausible mechanisms for the Ca(NTf2)2 mediated sulfur-fluorine activation process, specifically unraveling the calcium coordination complexes responsible for sulfur-fluorine bond activation. Furthermore, we probe various fluoride and product inhibition equilibria to provide new hypotheses for why stoichiometric Ca2+ is needed. Results from this computational study will be presented.

Computational investigations into the mechanism of Lewis-acid mediated activation of sulfur(VI) fluorides

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.