We report a mechanistic investigation of calcium bistriflimide-mediated sulfur(VI)–fluoride exchange (SuFEx) between sulfonyl fluorides and amines. We determine the likely pre-activation resting state─a calcium bistriflimide complex with ligated amines─thus allowing for corroborated calculation of the SuFEx activation barrier at ∼21 kcal/mol, compared to 21.5 ± 0.14 kcal/mol derived via kinetics experiments. Transition state analysis revealed: (1) a two-point calcium-substrate contact that activates the sulfur(VI) center and stabilizes the leaving fluoride and (2) a 1,4-diazabicyclo[2.2.2]octane additive that provides Brønsted-base activation of the nucleophilic amine. Stable Ca–F complexes upon sulfonamide formation are likely contributors to inhibited catalytic turnover, and a proof-of-principle redesign provided evidence that sulfonamide formation is feasible with 10 mol % calcium bistriflimide.
Han, B.; Khasnavis, S. R.; Nwerem, M.; Bertagna, M.; Ball, N. D.; Ogba, O. M. Calcium Bistriflimide-Mediated Sulfur(VI)–Fluoride Exchange (SuFEx): Mechanistic Insights toward Instigating Catalysis. Inorg. Chem. 2022. https://doi.org/10.1021/acs.inorgchem.2c01230
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