Total Synthesis of (+)-7,11-Helianane and (+)-5-Chloro-7,11-helianane through Stereoselective Aromatic Claisen Rearrangement

The aromatic bisabolene sesquiterpene of marine origin (+)-7,11-helianane (1) and its moderately cytotoxic halogenated relative (+)-5-chloro-7,11-helianane (3) have been synthesized by a concise, stereoselective route. By capitalizing on a palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) reaction, followed by a thermal (uncatalyzed) aromatic Claisen rearrangement, which allowed for the installation of the required benzylic stereocenter, the aforementioned natural products were secured in 80 % ee, with almost complete transfer of stereochemical information during the [3,3] sigmatropic process. The enantioselective total synthesis confirmed the recently proved (S) absolute configuration for (+)-7,11-helianane (1) and demonstrated the same configuration, for the first time, in the case of (+)-5-chloro-7,11-helianane (3).