Cost-Efficient, Multigram Scalable Synthesis of Shelf-Stable Electrophilic (Phenylsulfonyl)difluoromethylating Reagents

An easy-to-handle protocol for the synthesis of an efficient electrophilic (phenylsulfonyl)­difluoromethylating reagent, namely, the S-([phenylsulfonyl]­difluoromethyl)-dibenzothiophenium salt I, is depicted. The latter was synthesized on approximately 40 g scale in a three-step/one-purification sequence from commercially available or easy-to-synthesize starting materials with an estimated global prize of about 10.6 €/g. The bench-stable reagent I was found to be air- and moisture-tolerant. By changing the counter anion, a small library of electrophilic sources (reagents I–III) is now available for the (phenylsulfonyl)­difluoromethylation reaction. Differential scanning calorimetry (DSC) measurements have been also carried out on the different salts (I–III) along with a key intermediate to ensure a safe process.