Scalable Synthesis of the Amber Odorant 9-<i>epi</i>-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction

Abstract

A novel biomimetic nucleophilic bromocyclization reaction is used in the key step of a new and straightforward synthesis of 9-epi-Ambrox, an organic compound of high interest and value in the context of fragrances. This strategic reaction allows access to 9-epi-Ambrox on a gram scale from a dienyne derivative, easily available from geraniol, following a sequence of seven steps (35% global yield) with just one purification process. Both enantiomers of the molecule were obtained by a challenging enzymatic resolution.