Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via Catalytic C−H Bond Activation

The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C−H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C−H bond functionalization and represents the first application of this C−H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.