Synthetic Approach toward (–)-Tetrodotoxin via Construction of the Bicyclo[2.2.2]octane Skeleton

Abstract

AbstractA synthetic approach toward (–)-tetrodotoxin (TTX) is described. Our approach features a stereoselective construction of the TTX core structure using the bicyclo[2.2.2]octane skeleton which was constructed via intramolecular Diels–Alder reaction of an o-quinone monoketal having the key functional groups. The robust asymmetric synthesis was achieved by an iridium-catalyzed dynamic kinetic resolution (DKR) of the aryl vinyl carbinol that could be easily prepared from a simple aromatic compound.