Fluorodesulfurization of Thionobenzodioxoles with Silver(I) Fluoride

Abstract

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.

Emergence of Ag as a Catalyst of Choice for Fluorination and Trifluoromethylation Reactions

“…In this regard, Friesen and co-workers in 2020 developed an efficient strategy for their synthesis using easily available catechols (193) in two steps (Scheme 59) through conversion into thionobenzodioxoles (194), followed by desulfurative fluorination with silver(I) fluoride. [143] To have insight into the reaction pathway, an interesting intermediate oxocarbenium ion (197) was detected by 19F NMR spectroscopy in case of amino acid derivatives (197a, 197b). Based on the above observation, a plausible reaction mechanism was proposed which was initiated by the nucleophilic attack of fluoride ion on thionobenzodioxoles (194) resulted in the formation of oxocarbenium ion (197) (Scheme 60).…”

“…Difluorobenzodioxole (195) being important class of compounds, however, their synthesis is challenging due to the use of hazardous reagents and limited substrate scope. In this regard, Friesen and co‐workers in 2020 developed an efficient strategy for their synthesis using easily available catechols (193) in two steps (Scheme 59) through conversion into thionobenzodioxoles (194), followed by desulfurative fluorination with silver(I) fluoride [143] …”

“…The trifluoromethyl group (−CF 3 ) containing compounds are being efficiently used in medicinally important molecules because the presence of −CF 3 functionality can enhance the solubility, stability and binding affinity due to the presence of electronegative −F atom [153–156] . To avail this functional group in desired compounds several efforts have been made, of which transition metal catalyzed reaction are found to be most studied and effective …”

Unexpected Mechanism of Biodegradation and Defluorination of 2,2-Difluoro-1,3-Benzodioxole by Pseudomonas putida F1

“…1 ). Many other DFBD-based difluoroethers are in commercial use currently ( 11 ). The difluoromethylene group is designed into ring structures because it prolongs the lifetime of the compounds in both the human body and the environment.…”