Chemistry
Computational Investigation of the Factors Precluding Catalytic Turnover in Ca(NTf2)2 Mediated Sulfur(VI) Fluoride Activation
Presenter(s): Brian Han, Matthew Nwerem
Advisor(s): Dr. O. Maduka Ogba
Nitrogen-containing sulfur(VI) compounds are commonly used in the pharmaceutical industry to combat bacterial infections. Synthesis of these compounds is typically facilitated by nucleophilic attack of a sulfur(VI) chloride pre-cursor by an amine nucleophile. However, the relative instability of sulfur(VI) chlorides makes selective synthesis challenging in the presence of competing nucleophiles, and hence precludes late-stage functionalization of complex natural products. Sulfur(VI) fluorides have become an attractive alternative to the chloride analogs given the increased selectivity that can be achieved with these precursors. Our collaborators succeeded in synthesizing nitrogen-containing sulfur(VI) compounds under mild condition using a myriad of sulfur(VI) fluorides in the presence of amine nucleophiles and mediated by calcium triflimide – Ca(NTf2)2. This contrasts conventional methods where strong base/nucleophiles with elongated heating process were required. However, the mechanism for sulfur(VI)-fluoride activation using Ca(NTf2)2 is not known, and in most cases, stoichiometric calcium triflimide is required for the transformation. In my research project, we used quantum mechanical calculations to shed light on the reaction mechanism for Ca(NTf2)2 mediated sulfonyl-fluoride activation and specifically, to elucidate the factors preventing the catalytic turnover of Ca(NTf2)2 in t-BuOH as solvent. In this talk, I will present the minimum energy pathway for Ca(NTf2)2 mediated sulfur(VI) fluoride activation, and our current hypothesis for the origins of inhibition in this reaction.