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.

Synthesis of Trifluoromethyl-Substituted Allenols via Catalytic Trifluoromethylbenzoxylation of 1,3-Enynes

“…The trifluoromethyl (CF 3 ) group functions as an excellent bioisostere of the methyl group in medicinal chemistry, owing to its potential to improve the metabolic stability, bioavailability, and cellular membrane permeability of molecules . Accordingly, incorporation of a trifluoromethyl group into molecular skeletons has attracted significant interest for organic synthesis. − Allenol is a versatile synthon that undergoes diverse transformations, including eliminations, substitutions, and rearrangements (Figure A) . Therefore, a CF 3 -substituted allenol could be a multipurpose building block that allows expedited access to CF 3 -substituted compounds with diverse molecular skeletons. , …”

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.…”