Silver-Catalyzed C–H Aryloxydifluoromethylation and Arylthiodifluoromethylation of Heteroarenes

Abstract

The oxidative C–H aryloxydifluoromethylation and arylthiodifluoromethylation of heteroaromatic compounds through the decarboxylation of easily accessible aryloxydifluoroacetic acids and arylthiodifluoroacetic acids, respectively, are disclosed. These reactions are promoted by the combination of catalytic AgNO3 and Selectfluor or K2S2O8 to give ArOCF2- and ArSCF2-substituted heteroaromatic compounds in moderate to high yields.

Direct C−H Radical Alkylation of 1,4‐Quinones

“…[24] In 2020, the AgNO 3 /Selectfluor system was used by Qing's group to introduce the CF 2 OAr motif from the corresponding difluoroacetic acids 14 in various heteroaromatic compounds and the 1,4-naphthoquinone 1 c (Scheme 8). [25] Noteworthy, the conventional use of persulfate as an oxidant did not yield any target product, making selectfluor an useful alternative.…”

Silver in C(sp2)‐H Functionalization

“…Early this year, Qing et al published an oxidative C À H aryloxydifluoromethylation and arylthiodifluoromethylation of heteroaromatic compounds via the decarboxylation of easily accessible aryloxydifluoroacetic acids and arylthiodifluoroacetic acid (Scheme 9). [14] These transformations were believed to undergo through a silver-catalyzed Minisci-type pathway.…”

Direct C−H Difluoroalkylation of Heteroarenes with Difluoroalkyl Carboxylic Acids

“…[15] In 2013, Baran and co-workers developed a radical method for direct difluoroethylation of heteroarenes using sodium difluoroethylsulfinate (MeCF 2 SO 2 Na). [15a] Recently, the Minisci-type fluoroalkylation of (hetero)arenes using CF 3 CO 2 H, [16] HCF 2 CO 2 H, [17] ArCF 2 CO 2 H, [18] and ArOCF 2 CO 2 H [19] have been reported. [20] Inspired by these works, we envisioned that the direct difluoroalkylation of heteroarenes with difluoroalkyl carboxylic acids (RCF 2 CO 2 H, R = alkyl) could be an alternative strategy for efficient synthesis of difluoroalkyled heteroarenes.…”

“…These results indicate that the reactivity of RCO 2 H with 2 a decreases in the following order: MeCH 2 CO 2 H MeCF 2 CO 2 H > MeCFHCO 2 H @ CF 3 CO 2 H. To further probe the reaction mechanism, we conducted the radical inhibition experiments (Scheme 5). In the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), a radical scavenger, the reaction was nearly inhibited, while the adduct of TEMPO and difluoroethyl radical was detected by GC-MS and 19 F NMR using PhCF 3 as internal standard. 19 F NMR (for details, see Supporting Information).…”

“…In the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), a radical scavenger, the reaction was nearly inhibited, while the adduct of TEMPO and difluoroethyl radical was detected by GC-MS and 19 F NMR using PhCF 3 as internal standard. 19 F NMR (for details, see Supporting Information). Furthermore, when an electron transfer scavenger butylated hydroxytoluene (BHT) was added under the standard conditions, the difluoroethylated product (3 a) was only obtained in a yield of 32%.…”