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

Abstract

AbstractThe 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).