We have developed a method for Pd-catalyzed direct C–H
arylation
of quinoline-8-carbaldehydes with either aryl iodides or aryl diazonium
salts for the synthesis of aryl quinolinyl ketones. Aryl iodide substituted
with an electron-donating group favors the reaction, whereas aryl
diazonium salt substituted with an electron-withdrawing group showed
excellent reactivity. A range of aryl quinolinyl ketones were synthesized
in good-to-excellent yields, with very good functional group tolerance.
Our methodology was successfully applied to synthesize highly potent
tubulin polymerization inhibitors and can be easily scaled up to a
gram scale.