Generation of diverse 1-imidazolylisoquinolines via silver triflate-catalyzed reaction of 2-alkynylbenzaldoxime with imidazole

Abstract

Diverse 1-imidazolylisoquinolines are generated through a silver triflate-catalyzed cascade reaction of 2-alkynylbenzaldoxime with imidazole or benzoimidazole using parallel diversity-oriented synthesis. A small library of 1-imidazolylisoquinolines can be constructed efficiently under mild conditions. A plausible mechanism is proposed. We discovered that the presence of silver triflate and bromotrispyrrolidinophosphonium hexafluorophosphate (PyBroP) is essential for the reaction transformation. In the reaction process, treatment of 2-alkynylbenzaldoxime with silver triflate affords isoquinoline-N-oxide. Then, isoquinoline-N-oxide acts as a nucleophile to attack PyBroP to replace the bromide. Subsequently, an intermolecular nucleophilic addition of imidazole and further deprotonation take place to produce the desired 1-imidazolylisoquinolines. A range of great diversity could be easily introduced under the standard conditions during the reaction process.