Palladium-Catalyzed Chelation-Assisted Aldehyde C-H Bond Activation of Quinoline-8-carbaldehydes: Synthesis of Amides from Aldehydes with Anilines and Other Amines.

A palladium-catalyzed chelation-assisted direct aldehyde C-H bond amidation of quinoline-8-carbaldehydes with an amine was developed under mild reaction conditions. A wide range of amides were obtained in good to excellent yields from aldehyde with a variety of aniline derivatives and aliphatic amines. Our methodology was successfully applied to synthesize known DNA intercalating agents and can be easily scaled up to a gram scale.

Palladium-Catalyzed Directed Aldehyde C-H Arylation of Quinoline-8-carbaldehydes: Exploring the Reactivity Differences between Aryl (Pseudo) Halides.

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.