NBS-mediated bromination and dehydrogenation of tetrahydro-quinoline in one pot: scope and mechanistic study

Abstract

A facile and general approach was developed for the efficient construction of functionalized bromoquinolines by the dehydrogenation of tetrahydroquinolines using NBS as the electrophile and as oxidant. The cascade transformation proceeded with good functional group tolerance under metal-free conditions with a short reaction duration. Various tetrahydroquinolines bearing either electron-rich or electron-deficient groups at different positions were successfully converted into the corresponding target products in moderate to high yields under mild conditions. It is worth noting that the obtained polybromoquinolines could further undergo classic metal-catalyzed cross-coupling reactions with good regioselectivity. The Sonagashira coupling reaction occurred regioselectively in the C-6 position of the obtained products followed by a Suzuki coupling reaction to give multifunctionalized quinolines. The mechanism indicated that electrophilic bromination/radical dehydrogenation sequences occurred in one pot.