The first total synthesis of (±)-annosqualine by means of oxidative enamide–phenol coupling: pronounced effect of phenoxide formation on the phenol oxidation mechanism

The first total synthesis of a spiro-isoquinoline alkaloid, (±)-annosqualine, was established by employing an enamide–phenol coupling of a 1-methylene-1,2,3,4-tetrahydroisoquinoline derivative with a hypervalent iodine reagent, where the formation of the phenoxide was recognized to be an essential step for the reaction of the phenolic hydroxyl group with the hypervalent iodine reagent leading to the formation of the desired product.