Total Synthesis of (+)-Iresin

The first asymmetric total synthesis of (+)-iresin (<b>4</b>), an historically important <i>ent</i>-Drimane sesquiterpene lactone, was realized from aldehyde <b>3</b> via cyclic orthoester <b>6</b> in 5 steps. Notable transformations in this synthesis include a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer–Villiger oxidation–olefin epoxidation–epoxy ester cyclization, regioselective Burgess dehydration, and regioselective Fétizon oxidative lactonization