Asymmetric Total Synthesis of (-)-Plicatic Acid via a Highly Enantioselective and Diastereoselective Nucleophilic Epoxidation of Acyclic Trisubstitued Olefins

The first total synthesis of (-)-plicatic acid has been achieved by a concise and enantiosetective route. In this synthesis, a conceptually new strategy featuring an A asymmetric epoxidation-intramolecular epoxy-ring-opening Friedel-Crafts reaction sequence was developed for the stereoselective construction of the 2,7'-cyclolignane skeleton bearing contiguous quaternary-quaternary-tertiary stereocenters. The implementation of this strategy was enabled by the development of a modified protocol for the Seebach epoxiclation with TADOOH, which affords an unprecedented, highly enantiosetective and diastereoselective epoxiclation with a range of alpha-carbonyl-B-substituted acrylates 3.