Unexpected PF6 Anion Metathesis during the Bischler-Napieralski Reaction: Synthesis of 3,4-Dihydroisoquinoline Hexafluorophosphates and Their Tetrahydroisoquinoline Related Alkaloids

A series of N-phenethylcinnamamides were subjected to the Bischler-Napieralski reaction to furnish diverse 1-styryl-3,4-dihydroisoquinolines. We noticed that the desired products were unstable when the reaction was performed under conventional solvent conditions. However, when [bmim]PF (6) was used as the reaction media, the nature of the Bischler-Napieralski reaction promoted an unusual in situ ionic interchange between this ionic liquid and the dihydroisoquinoline core that led to the stabilization of the desired 1-styryl-3,4-dihydroisoquinolines, allowing their isolation as hexafluorophosphate salts. Finally, the one-pot reduction/reductive methylation process afforded the N -methyl derivatives, establishing that our findings can be an efficient and useful strategy for the concise synthesis of tetrahydroisoquinoline alkaloids.