Multimodal S(VI) Exchange Click Reactions Derived from SF Moieties: Comparative Kinetics and Stereochemistry of SuFEx and SuPhenEx Reactions.

The reaction mechanism of multimodal SuFEx and SuPhenEx click chemistries was investigated in detail for substitution of both the first and second fluoride or -nitrophenolate leaving groups in ∼RN = SOF and RN = SOF(-NO-phenol) substrates by temperature-dependent kinetics and density functional theory (DFT) calculations. Both the DFT calculations and the experimentally derived Δ indicate relatively small values for the activation enthalpies (4-15 kcal/mol), but almost constant and significant values of -Δ (10-14 kcal/mol). This indicates that depending on the precise nucleophile and S(VI) core, the reaction is either controlled by a mixture of enthalpy and entropy or basically is dominated by entropy alone. Finally, we show using chiral HPLC and X-ray crystallography that the SuFEx reaction on chiral RN = SOF(-substituted-phenol) substrates also proceeds enantiospecifically, opening up also multimodal click chemistry to chiral applications in chemical biology and materials science.