In addition to natural-occurring compounds, pharmaceutical agents such as chlorphenesin, a muscle relaxant, and ospemifene, a selective estrogen receptor modulator, were successfully converted to their difluoromethylated analogues (61 and 62, 64% and 72% yield, respectively). These two examples demonstrated the compatibility of aryl and alkyl chloride bonds with this approach. Idebenone, a benzoquinone-containing molecule that was originally designed for the treatment of cognitive defects, could be difluoromethylated with the benzoquinone group unaffected (63, 71% yield). Tedizolid, an antibiotic that incorporated a tetrazole, a pyridine, and an oxazolidone ring, was transformed in good efficiency (64, 65% yield). Ticagrelor, a top-selling blood thinner that consisted of a diol, a thioether, a secondary amine and a triazolo [4,5,-d]pyrimidine scaffold, was converted to its CF2H analogue in a 65% yield (65). Three cholesterol-lowering statins, including simvastatin, pitavastatin, and atorvastatin, all produced the desired CF2H products in good yields (66 to 68, 61% to 74% yield). It is noteworthy that the stereoisomers of these CF2H-lactones could be easily separated via silica column chromatography, thus potentially enabling structure-activity relationship studies. Finally, this protocol was applied to the difluoromethylation of glucoside compounds, including raspberry ketone glucoside (69, 64% yield), dapagliflozin (70, 58% yield) and empagliflozin (71, 60% yield), the latter two of which were among the top-selling pharmaceuticals in 2020 for the treatment of diabetes. The tolerance of unprotected triol groups further highlighted the mild conditions of the aryl radical activation strategy. Considering that CF2H groups could serve as the bioisoteres of hydroxyl groups, this difluoromethylation approach should enable the rapid synthesis and evaluation of bioisoteres of drug candidates.