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

J Org Chem. 2022 Dec 16;87(24):16343-16350. doi: 10.1021/acs.joc.2c02011. Epub 2022 Nov 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes
  • Catalysis
  • Iodides
  • Ketones
  • Molecular Structure
  • Palladium*
  • Quinolines*

Substances

  • Palladium
  • Aldehydes
  • Iodides
  • Ketones
  • Quinolines