Photoredox‐Catalyst‐Enabled para‐Selective Trifluoromethylation of tert‐Butyl Arylcarbamates

Abstract

The direct incorporation of a trifluoromethyl group on an aromatic ring using a radical pathway has been extensively investigated. However, the direct highly para‐selective C−H trifluoromethylation of a class of arenes has not been achieved. In this study, we report a light‐promoted 4,5‐dichlorofluorescein (DCFS)‐enabled para‐selective C−H trifluoromethylation of arylcarbamates using Langlois reagent. The preliminary mechanistic study revealed that the activated organic photocatalyst coordinated with the arylcarbamate led to para‐selective C−H trifluoromethylation. Ten‐gram scale reaction performs well highlighting the synthetic importance of this new protocol.

Direct Perfluoroalkylation of C−H Bonds in (Hetero)arenes

“…Very recently, the Shi and Zhao group reported a para-selective trifluoromethylation of aryl carbamates (Scheme 94, Equation (3)). [217] This photoinduced process relies on the light activation of 4,5-dichlorofluorescein that is used as an organic photocatalyst which coordinates with the aryl carbamate to lead to the desired para-selectivity. Upon light activation and oxidation with K 2 S 2 O 8 , a 4,5-dichlorofluorescein radical cation species would be formed.…”

“…Recombination of the trifluoromethyl radical species and the indazole radical cation and further loss of a proton would finally give the trifluoromethylation indazole (Scheme 94, Equation (2)). Very recently, the Shi and Zhao group reported a para ‐selective trifluoromethylation of aryl carbamates (Scheme 94, Equation (3)) [217] . This photoinduced process relies on the light activation of 4,5‐dichlorofluorescein that is used as an organic photocatalyst which coordinates with the aryl carbamate to lead to the desired para ‐selectivity.…”

Iron‐Catalyzed Trifluoromethylation of Indole‐Tethered Alkene Enables Synthesis of CF3‐Containing Spiroindolenines and Tetrahydrocarbazoles

“…The spiroindolenines 2 a or tetrahydrocarbazole 3 ae was not detected, and the TEMPO adduct 6 was observed by 19 F NMR. When 1,1-diphenylethylene was used as the radical trap, compounds 7 [12] and 8 [13] were formed and detected by 19 F NMR (Scheme 4c, 4d). These results indicated that the trifluoromethyl radical could be the reactive intermediate responsible for this reaction under the standard reaction conditions.…”

para‐Selective Radical Trifluoromethylation of Benzamide Derivatives via Iminium Intermediates

“…We assume that one of the important reasons for poor site‐selectivity is the ambiphilic nature (electrophilic and nucleophilic) of CF 3 radical [19] . Recently, Zhao's group demonstrated a photocatalyst‐enabled para ‐selective C−H trifluoromethylation of tert ‐butyl arylcarbamates via a radical/radical cross‐coupling pathway [20] . However, to our knowledge, para ‐selective C−H trifluoromethylation of electron‐deficient aromatic carbonyl compounds has never been reported and is highly changeling as the CF 3 radical is typically considered as an electrophilic species for aromatics.…”