Selective and Efficient Structural Elaboration of 2‐(Trifluoromethyl)quinolinones

The acid‐catalyzed cyclization‐condensation between anilines and ethyl 4,4,4‐trifluoroacetoacetate affords 1,4‐dihydro‐2‐trifluoromethyl‐4 H ‐4‐quinolinones ( 1 ), which can easily be converted into 4‐bromo‐2‐(trifluoromethyl)quinolines. These undergo halogen/metal exchange, generating 2‐trifluoromethyl‐4‐quinolyllithiums, when treated with butyllithium, and hydrogen/metal exchange, generating 4‐bromo‐2‐trifluoromethyl‐3‐quinolyllithiums, when treated with lithium diisopropylamide. Trapping of the latter intermediates provides 3‐functionalized products that may be further elaborated by electrophilic substitution of the bromine atom. A few unexpected findings resulted from these investigations, the most noteworthy being an unprecedented buttressing effect and a counterintuitive halogen reactivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)