Herein, we report a catalytic 4 + 2 annulation between trifluoromethyl allyl carbonates and isatic acids that provides direct access to 3-trifluoroethyl-4-carboxylate quinolines. The transformation proceeds smoothly under mild conditions and accommodates a broad range of electron-donating, electron-withdrawing, and sterically demanding substituents. In addition, a one-pot protocol enables efficient conversion of the annulation products into 3-trifluoroethyl-4-amido quinolines under the same reaction conditions. The synthetic versatility of this strategy is further demonstrated through the one-pot preparation of a trifluoroethyl analogue of brequinar, as well as the streamlined synthesis of trifluoroethylated analogues of bioactive scaffolds.
Sateesh et al. (Sun,) studied this question.