Approach to Tetrodotoxin via the Oxidative Amidation of a Phenol

Abstract

An approach to tetrodotoxin that relies on the oxidative amidation of methyl 4-hydroxyphenylacetate as a key step is described. The stereoselective introduction of a beta-hydroxynitrile functionality on one of the double bonds of the emerging dienone is achieved through an intramolecular nitrile oxide cycloaddition-fragmentation sequence.