The development of two highly reactive electrophilic trifluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide (1g) and (trifluoromethyl)(3-chlorophenyl)bis(carbomethoxy)methylide (1j) through structure-activity study was described. Under mild conditions, reagent 1g reacted with β-ketoesters and silyl enol ethers to give α-trifluoromethylated-β-ketoesters or α-trifluoromethylated ketones in high yields. In addition, reagent 1g could serve as a trifluoromethyl radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoromethylation of electron-rich indoles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with styrene derivatives. On the other hand, as a complimentary, under reductive coupling conditions, reagent 1j reacted with a variety of (hetero)aryl iodides for the formation of trifluoromethylated (hetero)arenes.
A kilogram-scale process for the
preparation of a potentially broadly
applicable electrophilic trifluoromethylating reagent, (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide
(YlideFluor), was reported. The reagent was prepared in three steps
from a cheap, commercially available starting material, and the price
of the reagent is estimated to be as low as $1.5/g. Application of
the reagent in the preparation of trifluoromethylated derivatives
of two drug molecules in the gram scale was demonstrated.
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