Transition State Stabilization by SCF2-H•••O Bifurcated Hydrogen Bond

The difluoromethylthio group (SCF2H), which is generally considered a highly lipophilic weak hydrogen bonding donor, has attracted special interest from the pharmaceutical and agrochemical industry. Remarkably, there have been relatively few literature investigations of SCF2H hydrogen bonding interactions. Here, we report the determination of the hydrogen bond acidity parameter A of the SCF2H in the most popularly used electrophilic difluoromethylthiolating reagent. We present kinetic and computational evidence of the RSCF2-H center dot center dot center dot O2 bifurcated hydrogen bond for stabilizing the SCF2H-transferring transition state, which could cause a reversal of apparent electrophilic reactivity of difluoromethylthiolating and trifluoromethylthiolating reagents. Solvent effects on the RSCF2-H center dot center dot center dot O2 bifurcated hydrogen bonds will also be discussed.

Automated summary

This study describes the determination of the hydrogen bond acidity parameter A of the difluoromethylthio group (SCF2H) in the commonly used electrophilic difluoromethylthiolating reagent. Evidence of the RSCF2-H...O2 bifurcated hydrogen bond for stabilizing the SCF2H-transferring transition state is presented, which can lead to a reversal of the apparent electrophilic reactivity of difluoromethylthiolating and trifluoromethylthiolating reagents. The solvent effects on the RSCF2-H...O2 bifurcated hydrogen bonds are also discussed.