Gold(I)-catalysed intramolecular hydroamination of α-quaternary alkynes: synthetic studies towards spiroimine marine toxins

Abstract

Cyclic spiroimines form an essential component of the bioactive pharmacophore in a number of potent fast-acting marine biotoxins, including the pinnatoxins, gymnodimine and the spirolides. These present a significant challenge for the total synthesis of this class of natural products. A novel approach to these cyclic spiroimines based on metal-catalysed hydroamination of spiroaminoalkyne precursors is reported herein. Au(PPh3)SbF6 was found to effect the formation of bench-stable 5,6- and 6,6-spiroimine systems in high yields, although the 7,6-analogue remained elusive. To the best of our knowledge these are the first reported examples of α-quaternary cyclic imines formed via alkyne hydroamination.