N-Activation of 2-PySO2CF2H for Electrophilic Difluoromethylthiolation of Electron-Rich Heteroarenes

Difluoromethyl 2-pyridyl sulfone (2-PySO2CF2H) is a readily accessible, cost-effective, and versatile reagent with broad applications in fluoroalkylation and fluoroolefination. Here, we unveil a novel application of 2-PySO2CF2H in electrophilic difluoromethylthiolation. Key to this advance is the strategic N-activation of 2-PySO2CF2H to generate stable N-methylpyridinium salt and pyridine N-oxide derivatives. When synergistically combined with (EtO)2P(O)H/TMSCl, these activated sulfones facilitate efficient difluoromethylthiolation of electron-rich heteroarenes, such as indoles and pyrroles. This research not only introduces a new strategy for electrophilic difluoromethylthiolation but also provides new insights into the mechanism of (EtO)2P(O)H/TMSCl-mediated difluoromethylthiolation reactions.