Copper(II)-Catalyzed Direct C–H Trifluoroethylation of Heteroarenes

Abstract

Trifluoroethyl (CH2CF3) is an important functional group in many pharmaceutical and agrochemical compounds. Herein, we report an efficient method for the copper-catalyzed direct trifluoroethylation of heteroarenes. The reaction exhibited good compatibility to various substrates, and the desired products were obtained in good yields. Preliminary mechanistic investigations indicate the trifluoroethyl radical is involved in the catalytic circle. Moreover, the late-stage modification of bioactive molecules further confirmed the practical applications of this method.

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

“…Coordination of the aminoquinoline with the copper catalyst and subsequent deprotonation yielding to the formation of a 5‐membered chelate was described as the key factor for the observed regioselectivity, the perfluoroalkyl radical species – generated from the reaction of perfluoroalkyl sulfinate salt and azobisisobutyronitrile – thereby reacting at the activated C5‐position (Scheme 50, Equation (2)). A similar system was also reported by the Li group for the selective trifluoroethylation of heteroarenes such as indoles, pyrroles, furans and (benzo)thiophenes bearing a pyrimidine or pyridine directing group with copper(II) acetate as the catalyst [132] …”

“…A similar system was also reported by the Li group for the selective trifluoroethylation of heteroarenes such as indoles, pyrroles, furans and (benzo)thiophenes bearing a pyrimidine or pyridine directing group with copper(II) acetate as the catalyst. [132]…”

Switchable Reductive N-Trifluoroethylation and N-Trifluoroacetylation of Indoles with Trifluoroacetic Acid and Trimethylamine Borane

“…16 Recently, Li and co-workers reported a copper-catalyzed radical trifluoroethylation of indoles at the C2 position with CF 3 CH 2 SO 2 Na (Scheme 1b). 13 Generally, these developed trifluoroethylations of the indoles took place at the C2 or C3 position, while trifluoroethylation at the N1 position of the indoles was rarely reported.…”

“…In this context, extensive methods for trifluoromethylation have been well developed, while the trifluoroethylation reaction has less been explored. During recent decades, a few trifluoroethylating agents such as CF 3 CF 2 I, (CF 3 CF 2 SO 2 ) 2 Zn, mesityl-(2,2,2-trifluoroethyl) iodonium salt, 2,2,2-trifluorodiazoethane, and CF 3 CH 2 SO 2 Na have been developed, which provide opportunities for exploring novel trifluoroethylation reactions. In 2015, Novák and co-workers reported the direct trifluoroethylation at the C3 position of indoles with 2,2,2-trifluoroethyl­(mesityl)-iodonium triflate (Scheme a) .…”

“…Subsequently, a palladium-catalyzed trifluoroethylation of indoles at the C2 position with CF 3 CF 2 I was demonstrated by Liu and co-workers (Scheme b) . Recently, Li and co-workers reported a copper-catalyzed radical trifluoroethylation of indoles at the C2 position with CF 3 CH 2 SO 2 Na (Scheme b) . Generally, these developed trifluoroethylations of the indoles took place at the C2 or C3 position, while trifluoroethylation at the N1 position of the indoles was rarely reported.…”