Asymmetric Total Synthesis of (+)-Karanone: An Important Aroma Compound in Fine Agarwood

The first asymmetric total synthesis of (+)-karanone, a key aroma compound in high-grade agarwood ("Kyara"), was accomplished in 17 steps from 4-penten-2-ol. The key stereocenters at C7, C4, and C5 were introduced via asymmetric aldol condensation and Ireland-Claisen rearrangement. The oxygen-functional group at C8 was formed through oxidative rearrangement, and the bicyclic core of (+)-karanone was constructed by ring-closing metathesis. Two related compounds, namely (+)-4-epi-karanone and (+)-warburgiadione, were also synthesized. Studies of the structure-odor relationship among (+)-karanone, (+)-4-epi-karanone, and (+)-warburgiadione were also performed.