HFIP-Empowered One-Pot Synthesis of C4-Aryl-Substituted Tetrahydroquinolines with Propargylic Chlorides and Anilines

Abstract

Transition-metal-free, practical one-pot synthesis of C4-aryl-substituted tetrahydroquinolines from simple anilines and readily accessible propargylic chlorides has been developed. Activation of the C-Cl bond by 1,1,1,3,3,3-hexafluoroisopropanol turned out to be the key interaction, which allowed C-N bond formation under an acidic medium. Propargylated aniline is formed as an intermediate via propargylation, and subsequential cyclization and reduction gave 4-arylated tetrahydroquinolines. To demonstrate the synthetic utility, total syntheses of aflaquinolone F and I have been accomplished. © 2023 American Chemical Society.