Exploration of the Synthetic Potential of Electrophilic Trifluoromethylthiolating and Difluoromethylthiolating Reagents

The electrophilicity parameters (E) of some trifluoromethylthiolating and difluoromethylthiolating reagents were determined by following the kinetics of their reactions with a series of enamines and carbanions with known nucleophilicity parameters (N, s(N)), using the linear free-energy relationship log k(2)=s(N)(N+E). The electrophilic reactivities of these reagents cover a range of 17 orders of magnitude, with Shen and Lu's reagent 1a being the most reactive and Billard's reagent 1h being the least reactive electrophile. While the observed electrophilic reactivities (E) of the amido-derived trifluoromethylthiolating reagents correlate well with the calculated Gibbs energies for heterolytic cleavage of the X-SCF3 bonds (Tt(+)DA), the cumol-derived reagents 1 f and 1 g are more reactive than expected from the thermodynamics of the O-S cleavage. The E parameters of the tri/difluoromethylthiolating reagents derived in this work provide an ordering principle for their use in synthesis.