A Unified Approach for the Enantioselective Synthesis of the Brominated Chamigrene Sesquiterpenes

The brominated chamigrene sesquiterpenes constitute a large subclass of bromocyclohexane‐containing natural products, yet no general enantioselective strategy for the synthesis of these small molecules exists. Herein we report a general strategy for accessing this family of secondary metabolites, including the enantioselective synthesis of (−)‐α‐ and (−)‐ent‐β‐bromochamigrene, (−)‐dactylone, and (+)‐aplydactone. Access to these molecules is enabled by a stereospecific bromopolyene cyclization initiated by the solvolysis of an enantiomerically enriched vicinal bromochloride. Dihalides light the way: A stereospecific bromopolyene cyclization of an enantiomerically enriched bromochloride was developed as a highly general approach to the brominated chamigrene sesquiterpenes (see scheme). The total synthesis of (+)‐aplydactone was completed by an intramolecular [2+2] cycloaddition.