Difluorobenzodioxole is an important functional group found in both pharmaceuticals and agrochemicals. The late-stage introduction of this functional group is challenged by typical fluorination conditions of HF and strong oxidants. Here, we demonstrate that a range of difluorobenzodioxoles can be prepared from catechols in two steps through conversion into thionobenzodioxoles, followed by desulfurative fluorination with silver(I) fluoride. These mild reaction conditions are compatible with a variety of functional groups and enable access to a range of functionalized difluorobenzodioxoles.

The difluoromethyl group plays an important role in modern medicinal and agrochemistry. While several difluoromethylation reagents have been reported, these typically rely on difluoromethyl carbenes or anions, or target specific processes. Here, we describe a conceptually unique and general process for OÀ H, NÀ H and CÀ H difluoromethylation that involves the formation of a transient dithiole followed by facile desulfurative fluorination using silver(I) fluoride. We also introduce the 5,6-dimethoxy-1,3-benzodithiole (DMBDT) function, which undergoes sufficiently rapid desulfurative fluorination to additionally support 18 Fdifluoromethylation. This new process is compatible with the wide range of functional groups typically encountered in medicinal chemistry campaigns, and the use of Ag 18 F is demonstrated in the production of 18 F-labeled derivatives of testosterone, perphenazine, and melatonin, 58.0 � 2.2, 20.4 � 0.3 and 32.2 � 3.6 MBq μmol À 1 , respectively. We expect that the DMBDT group and this 18 F/ 19 F-difluoromethylation process will inspire and support new efforts in medicinal chemistry, agrochemistry and radiotracer production.