Synthesis of 3-Haloquinolines via the Friedländer Reaction

Significance

Reported is a general method for the synthesis of 3-haloquinolines from ortho-aminocarbonyl compounds and α-haloketones. This Friedländer reaction was promoted by organosilanes, the choice of which proved crucial in some instances. Using α-fluoroketone substrates, the choice of organosilane did not matter and the 3-fluoroquinoline products were formed under standard conditions. However, for α-iodoketones, reductive deiodination occurred during the reaction to give 3-unsubstituted quinolines. With α-bromo- or -chloroketones, it was necessary to use TMSBr and TMSCl, respectively, as the organosilane was shown to be the source of the halide in the product. Alternatively, TMSOTf may be used to retain the α-halo substituent (except for an iodide). Using TMSI for bromo- and chloroketones resulted again in the formation of 3-unsubstituted quinolines. The yields are generally good, with some exceptions and the substrate scope was well studied.