Catalytic Asymmetric Total Synthesis of (−)-Actinophyllic Acid

Described
herein is a catalytic asymmetric total synthesis of (−)-actinophyllic
acid, with the key step being a chiral phosphine-catalyzed [3 + 2]
annulation between an imine and an allenoate to form a pyrroline intermediate
in 99% yield and 94% ee. The synthesis also features CuI-catalyzed
coupling between a ketoester and a 2-iodoindole to shape the tetrahydroazocine
ring; intramolecular alkylative lactonization; SmI2-mediated
intramolecular pinacol coupling between ketone and lactone subunits
to assemble the complex skeleton of (−)-actinophyllic acid;
and an unprecedented regioselective dehydroxylation.