Enantiocontrolled synthesis of (-)-9-epi-pentazocine and (-)-aphanorphine

We have developed novel asymmetric routes to (-)-9-epi-pentazocine and (-)-aphanorphine from a D-tyrosine derivative. The tricyclic frameworks of (-)-9-epi-pentazocine and (-)-aphanorphine were assembled stereoselectively via intramolecular Friedel-Crafts reaction of the corresponding bicyclic precursors, generated with titanium-promoted enyne cyclization and indium-initiated atom-transfer radical cyclization, respectively.