Total Synthesis of Virgatolide B via Exploitation of Intramolecular Hydrogen Bonding

A full account of the enantioselective total synthesis of virgatolide B is reported. Key features of the synthesis include an sp(3)-sp(2) Suzuki-Miyaura cross-coupling of a beta-trifluoroboratoamide with an aryl bromide, regioselective intramolecular carboalkoxylation, and a 1,3-anti-selective Mukaiyama aldol reaction. Intramolecular hydrogen bonding governed the regioselectivity of the key spiroketalization step, affording the natural product as a single regioisomer.