Radical Trifluoromethoxylation of Arenes Triggered by a Visible‐Light‐Mediated N−O Bond Redox Fragmentation

Abstract

As imple trifluoromethoxylation method enables non-directed functionalization of CÀHb onds on ar ange of substrates,providing access to aryl trifluoromethyl ethers.This light-driven process is distinctly different from conventional procedures and occurs through an OCF 3 radical mechanism mediated by ap hotoredoxc atalyst, whicht riggers an N À O bond fragmentation. The pyridinium-based trifluoromethoxylation reagent is bench-stable and provides access to synthetic diversity in lead compounds in an operationally simple manner.Scheme 1. Advances in late-stage arene trifluoromethoxylation.

Synthesis of Tri‐ and Difluoromethoxylated Compounds by Visible‐Light Photoredox Catalysis

“…In the same year, Togni and co‐workers independently developed and disclosed an elegant work on photocatalytic radical trifluoromethoxylation of (hetero)arenes using the pyridinium‐based trifluoromethoxylating reagent III (Scheme ) . III can be synthesized in one‐step in 63 % yield by trifluoromethylation of 4‐cyanopyridine N ‐oxide using Togni's reagent I and TMSNTf 2 ( N ‐trimethylsilyl‐bis(trifluoromethanesulfonyl)imide).…”

“… a) CW‐EPR studies. b) Proposed catalytic cycle for trifluoromethoxylation of arenes with III under visible‐light photoredox conditions …”

Visible‐Light Photoredox‐Catalyzed and Copper‐Promoted Trifluoromethoxylation of Arenediazonium Tetrafluoroborates

“…[11] Hu and co-workers developed trifluoromethyl benzoate (TFBz) as an ew trifluoromethoxylation reagent for the synthesis of trifluoromethyl aryl ethers. [13] Although progress has been made,with few exceptions,s trong oxidants are required or regioisomers are observed. [13] Although progress has been made,with few exceptions,s trong oxidants are required or regioisomers are observed.…”

“…Thed esired product 3a was obtained when aC u(OTf) solution in acetonitrile was stirred with TFMS (2a)a nd cesium fluoride for 1h at room temperature,f ollowed by addition of the diazonium salts and photoredox catalyst with continued stirring at À40 8 8Cf or 12 hours under irradiation with aw hite LED,a si llustrated in Table 1. They ield was also sensitive to the fluoride source,a nd CsF was the most effective (entries 7, 13,14). Next, different copper salts were evaluated.…”

“…When 4.0 equiv of TEMPO was added, no trifluoromethoxylated product was obtained, and the TEMPO-trapped intermediate (13)w as isolated in 74 %y ield. When 4.0 equiv of TEMPO was added, no trifluoromethoxylated product was obtained, and the TEMPO-trapped intermediate (13)w as isolated in 74 %y ield.…”